Functions
of Prefrontal
STEFAN
Cortex
in Animals
BRUTKOWSKI
Department of Neurophysiology,
The Nencki Institute of Ex-erimental
Biology,
Polish Academy of Sciences, Warsaw, and Laboratory of Animal Physiology,
University of Lodz, Lode, Poland
............................................
I. Anatomical
Considerations.
............................................
IL Behavioral Considerations.
A. Experimental
evidence for frontal cortex involvement
in somatomotor
and
..............................................
autonomic functions.
B. Experimental
evidence for frontal cortex involvement
in sensory functions.
.
C. Critique of concept of frontal lobe involvement
in highest psychical functions ............................................................
D. Hypoactivity
and hypoemotionality
(“stuporous”
behavior,
mutism, loss
of spontaneity
or initiative) .........................................
....................................................
E. Hyperactivity.
F. Locus of deficit reflecting hypo- and hyperactivity
states. ...............
G. Hyperreactivity ...................................................
H. Changes in affective behavior after frontal lesions. .....................
I. Impairment
of CR performance.
....................................
.........................................................
III. Conclusions.
I.
ANATOMICAL
72=
724
724
724
726
727
728
730
73=
739
740
74=
CONSIDERATIONS
Hines
(86) was the first to designate
the portion
of the frontal
cortex lying
rostra1 to the premotor
areas and frontal eyefields as “prefrontal
cortex.”
Recently
it has been appropriately
termed
the Ccnonmotor”
frontal
area (6), since it is
essentially
unrelated
to motor functions.
Despite
extensive
research
the homology
of the prefrontal
cortex is under
dispute.
Brodmann’s
(32) concept of the frontal region based on the presence of the
internal
granular
layer suggests that the prefrontal
area is a primate
characteristic
and should be confined
to the dorsolateral
surface of the hemisphere.
However,
it
is now generally
considered
that the cortex situated
on the ventral
and medial
aspects of the frontal
lobe, particularly
its orbital
sector, which
is essentially
agranular,
constitutes
a portion
of the prefrontal
cortex as well. Also, it has gradually become apparent
that a cortical area equivalent
to the primate
frontal granular
(109)
identifies
myeloarchitectonicortex is present in subprimates.
Thus Kreiner
tally the prefrontal
area in the dog as that delimited
by the anterior
rhinal
fissure,
the bottom
of the presylvian
fissure, its extension
over the dorsal ridge of the
hemisphere,
and, on the medial
aspect of the hemisphere,
by the genual fissure and
its extension
ventrally
from the genu of the corpus callosum.
Anatomical
assumption favoring
the view of the presence of the prefrontal
cortex in all mammals
is
compatible
with the physiological
and behavioral
evidence
indicating
that the
721
7’2
STEFAN
BRUTKOWSKI
Volume 45
“electrically
inexcitable”
frontal
cortex in lower species subserves many
of the
functions
attributed
to the primate
frontal granular
cortex (38, 105, I go).
Although
traditionally
described
as an “association”
area, the prefrontal
cortex has been recognized
as a projection
area of the dorsomedial
nucleus of the
thalamus
(4, 6, 28, 86, I 53, I 58, I 68, I 87, I go). Three systems of projections
from
the dorsomedial
nucleus to the prefrontal
cortex have been differentiated:
a) the
laterally
placed pars paralamellaris
to the frontal eyefields or area 8 of Brodmann;
b) the centrally
placed pars parvocellularis
to the dorsolateral
frontal cortex or area
FD of von Bonin and Bailey (29); and c) the medially
placed pars magnocellularis
to the orbital
cortex. This subdivision
was established
for the rhesus monkey
(6,
186, 187). However,
Akert
(6) maintains
that three similar
projection
systems
exist in the squirrel
monkey,
dog, and cat. This does not seem to be entirely
conclusive since the degeneration
in the thalamus
of carnivores
in Akert’s description
was identified
only after complete
prefrontal
lobe amputations,
which necessarily
involved
anatomically
different
parts of the prefrontal
area. The ultimate
determination
of the distribution
of the prefrontothalamic
connections
in carnivores
must await detailed
studies of brains with partial
cortical
lesions. Most recently
Akert (6) has demonstrated
that, in the rhesus monkey,
the dorsomedial
portion
of
the prefrontal
cortex is athalamic.
In a sense, therefore,
a part of the prefrontal
cortex may be regarded
as purely associative.
During
the past few decades many advances in knowledge
of the descending
pathways
from the prefrontal
cortex have been made. The most important
is the
recognition
of a dual-fiber
system to the limbic
and subcortical
structures.
It has
thus been established
(I 40) that the orbital
portion
of the frontal cortex is linked up
either directly
or via the magnocellular
division
of the dorsomedial
nucleus of the
thalamus
with both the amygdaloid
complex
and various hypothalamic
nuclei,
which in turn have connections
with the mesencephalic
reticular
formation;
the
dorsolateral
frontal
cortex, on the other hand, is closely associated with the hippocampal
system, the subthalamic
region, the rostra1 midbrain
tegmentum,
and the
rostra1 part of the central gray midbrain
substance.
From the findings
of Adey (I),
Adey and Meyer (2) and White,
Nelson and Foltz (I 93) it has become evident that,
in addition
to the recently
discovered
connections
from the dorsolateral
portion
of
the prefrontal
cortex,
the hippocampal
formation
receives
fibers through
the
fasciculus
cinguli
from the medial
prefrontal
cortex.
that the amygdaloid
complex,
the magnocelluNauta
(I 39, I 40) has reported
lar part of the thalamic
dorsomedial
nucleus, and the orbitofrontal
cortex constitute
a reciprocally
interconnected
system. It is also known from the evidence
given first
by Walker
(I 87) and later by Le Gros Clark and Meyer
(53, 54) that the magnocellular
division
of medialis
dorsalis receives ascending
projections
from the hypothalamus.
Using the Nauta
stain, Margala
and Grofova
(I 25) have found that the
frontohypothalamic
fibers in the cat originate
in the medial
prefrontal
cortex and
spread through
the area hypothalamica
lateralis
to the dorsal and lateral
portions
of the ventromedial
nucleus and the posterior
part of the hypothalamus.
The authors also traced diffusely
running
fibers from the premotor
cortex via the lateral
hypothalamic
area that, however,
do not make direct connections
with the medial
October 1965
FUNCTIONS
OF PREFRONTAL
CORTEX
723
hypothalamic
nucleus. There are thus clear anatomical
connections
from the hypothalamus
to the prefrontal
cortex via the dorsomedial
nucleus of the thalamus
and
direct efferent pathways from the cortex to the hypothalamus.
Moreover,
the magnocellular
part of the dorsomedial
nucleus is identified
as a nodal point linking
the
orbital
cortex with both the amygdala
and the hypothalamus.
On the other hand,
the parvocellular
part of the medialis
dorsalis
receives quite a dense projection
from the dorsolateral
prefrontal
cortex.
Nauta’s
work has also provided
anatomical
evidence
for the topographic
organization
of connections,
largely by the way of the fasciculus
uncinatus,
between
the prefrontal
and temporal
areas within
the “basal neocortex”
(I 72) : fibers from
the dorsal part of the dorsolateral
prefrontal
cortex have been found to reach the
superior
temporal
gyrus, whereas those originating
ventrally
lead to the middle
and inferior
temporal
gyri. Moreoever,
it has been indicated
that the uncinate
fasciculus
contains
fibers that arise in the amygdala
and the temporal
neocortex
and are oriented
toward the prefrontal
cortex. These findings
support
the earlier
anatomical
and physiological
data showing that the caudal part of the medial
and
basal frontal
cortex and the temporal
pole, including
the periamygdaloid
region
and the amygdala,
form a structurally
and functionally
integrated
system associforebrain
ated with the hypothalamus
(I 23, I 50, I 54, I 66, I 72). The mediobasal
structures
have recently
become
the focus of great interest
since it has been proposed that in connection
with some limbic
and subcortical
structures
they represent the highest level of autonomic
and emotional
organization
(69, I 22, 123, 143,
I 44).
Nauta
( I 40), considering
the cortico-limbic-subcortical
interrelations,
speculates on the possibility
that the entire prefrontal
cortex could be recognized
as a
control organ of the functions
elaborated
in the hypothalamus
and CCvisceral brain.”
In this context,
it is interesting
to note that the direct efferent connections
from
the orbital
cortex to the hypothalamus
suggested
to Le Gros Clark (53) that the
prefrontal
cortex might be a projection
area of the hypothalamus
in the same way
that the visual cortex is regarded
as a projection
area of the retina or the auditory
cortex of the cochlea.
Evidence
that
the prefrontal
cortex
has been offered by a few investigators
has shown that the orbitofrontal
cortex
has efferent
connections
with
(61, 73, 85, I 25, I 27, 140).
projects
on the ventrolateral
the striatum
Nauta
part
(140)
of the
head of the caudate nucleus, whereas the dorsolateral
subdivision
of the prefrontal
cortex has a close association
with the dorsolateral
part of the head of the caudate
nucleus. Also, fibers have been traced from the prefrontal
cortex, mostly from its
orbital
portion,
to the putamen
and claustrum.
Recently
an anatomical
connection
between
the frontal
cortex and the substantia nigra has been described
(93).
The evidence
thus indicating
the presence of two prefronto-limbic-subcortical
groupings
suggests that the orbital
and the dorsolateral
subdivisions
of the prefrontal cortex are implicated
in different
mechanisms.
However,
a clean functional
dichotomy
separable
cannot be expected
anatomically.
since these two systems
do not appear
to be entirely
STEFAN
724
II.
BEHAVIORAL
BRUTKOWSKI
Volume 45
CONSIDERATIONS
A. Experimental
Evidence for Frontal
Somatomotor and ‘Autonomic Functions
Cortex Involvement
in
Numerous
earlier
investigators
disclosed
the existence
of control
centers for
motor coordination
in the prefrontal
cortex.
Goltz (75-77),
Munk
(I 38), Bianchi
(24), Luciani
(I IS), and others found that animals
deprived
of the anterior
parts
of the frontal lobes lost the normal
integration
of certain bulbar and spinal reflexes
or showed ataxia in motor
performance
as well as paresis of delicate
and skilled
movements,
such as picking
up fruit and catching
fleas. More
recently
Shustin
(I 70) reported
a persistent
deficit in vocal reaction
(barking)
after frontal
lobectomy in the dog. According
to Shustin,
there was also often marked
disturbance
in chewing
and mastication
associated
with protraction
of the act of eating.
Difficulty in grasping
food and feeding was also found in rabbits
with lesions placed
in the medial surface of the hemisphere
on a 4-mm
stretch beginning
at the tip of
the frontal
poles (Zachwieja
and Balinska,
unpublished
data). After unilateral
removal of the frontal eyefield in the monkey
a transient
paralysis of conjugate
deviation of the eyes to the opposite
side has been described
(gg).
There is also considerable
evidence that damage
to the frontal cortex produces
marked
deviations
from normal
in gastrointestinal
activities
(48, 50, 72, I 28), sal( I I o), diuresis
(I 02), and thermal
regulation
(7,
ivation
(7, I 70, 184), micturition
589 59)*
On the other hand, some early (51, 89, go) and many more recent observations indicate
that damage
to the prefrontal
areas produces
slight or no alteration
of motor
and visceral mechanisms.
It seems highly
probable
that some of the behavioral
disturbances
assigned to the injury of the prefrontal
cortex were the result
instead of widespread
frontal damage.
This is particularly
likely with subprimates
in which parts of the prefrontal
cortex are relatively
inaccessible
and are therefore
difficult
to ablate selectively.
On the basis of current
physiological
and behavioral
data, it appears justified
to suggest that at least some changes in visceral and somatic functions
may be ascribed
to injury
of motor
or premotor
cortices. Apparently, in early and even in some recent cerebral
ablation
studies no sharp line was
drawn separating
the motor and nonmotor
cortex of the frontal lobe. We now have
evidence
that dogs do not exhibit
signs of disturbance
in gross motor
behavior
or
in coordination
of movements
when the premotor
areas are left intact and the lesion is confined
to the rostra1 parts of the frontal
lobe; and this is so with either
lobectomy
or cortical
ablation
(38).
B. Experimental
Evidence for Frontal
Cortex Involvement
in Sensory Functions
I) Gross sensory decficit. Disturbances
in sensory functions
in animals
with frontal
lobe ablations
were related initially
to hemianopsia
(24). Kennard
(96) found that
bilateral
ablation
of area 8 in the monkey
leads to transient
“object
blindness.”
Later an increased
susceptibility
to tactile
stimuli,
particularly
to restraints
on
October 1965
FUNCTIONS
OF PREFRONTAL
CORTEX
725
movement,
was indicated
(I 3, 60, 145, 167, I 70). However,
Smith
(I 71) and
Brutkowski
et al. (44) showed for the monkey
and dog, respectively,
that the site
of the critical
lesion producing
the elevation
of tactile sensibility
is confined
not to
the prefrontal
cortex but rather to the rostra1 cingulate
cortex.
2) Learning and discrimination.
Early literature
contains
little information
concerning impairment
of the ability
to learn or to associate after experimental
lesions
of the prefrontal
cortex. In 1902 Franz (64) showed that frontal
lobe damage
in
monkeys
and cats results in a temporary
loss of preoperatively
acquired
motor
habits,
and he concluded
that the prefrontal
cortex serves an important
role in
maintenance
of recently
established,
as opposed to longstanding,
associations.
In
contrast
Pavlov
(145) and his students indicated
that the prefrontal
areas are not
essential for elaboration
of those associations
referred to as “higher
nervous activities,” because dogs with large frontal
lobectomies
fail to show permanent
impairment on salivary conditioned
reflexes (CR’s) to the presentation
of either visual- or
acoustic-conditioned
stimuli
(CS’i).
The irreversible
loss of CR’s to tactile
CS’i
was ascribed to impairment
of the mechanism
underlying
the functions
of the motor
and skin analyzers -that
is, the receiving
areas of the sensorimotor
cortex. According to Pavlov,
an animal
with a frontal
lesion is deprived
of a considerable
amount
of somesthetic
information
and thus loses the ability
to react properly
to many environmental
cues. This general conclusion
does not conflict
with the earlier
statement that lesions in the frontal
lobe result in an increased
tactile
sensibility,
because Pavlov’s
statement
was based on findings
in animals
with massive lesions
involving
“the anterior
halves of both hemispheres.”
Recently
much evidence
has been provided
that complete
or partial
lesions
of the frontal
cortex, specifically
its lateral
portion,
in both primates
and subprimates produce
severe impairment
in learning
and performance
of a variety
of discrimination
tasks in all sensory modalities
(8, 55, 56, 65, 66, 78-80, 82, 83, 137,
I 76). Some of the most convincing
evidence
for the participation
of the prefrontal
cortex in learning
has been revealed
by stimulation
studies (I 73-175).
It has been
shown that, depending
on the voltage
settings, stimulation
may retard or facilitate
learning.
Rosvold
and Mishkin
and their associates (I 8, I 33, I 6 I) consider
the sensory
effect of a frontal
lesion on discrimination
acquisition
and retention
to be a misconception,
and they state that it is, in fact, a nonsensory
deficit that underlies
the
animal’s
discrimination
impairment.
Evidence
favoring
this interpretation
has
come from the experiments
by Battig et al. (I 8), in which monkeys
with lesions of
the lateral frontal
cortex show impairment
on successive but not on simultaneous
visual discrimination.
In fact, a similar
interpretation
was offered by Kalischer
(94) and Afanasev
(5) a long time ago. Using Bekhterev’s
associative-motor
type
of testing, which is an equivalent
of Pavlovian
classic motor-defensive
conditioning,
Afanasev clearly demonstrated
that dogs with prefrontal
lesions are not impaired
in learning
and retaining
a discrimination
task in a situation
in which either of two
acoustic,
visual, or tactile
CS’i, presented
randomly
in a successive order, elicits
one of two forefoot
CR’s reinforced
by an electric
shock to the relevant
forefoot.
Conversely,
a dog with a frontal lesion is markedly
impaired
in the type of discrimination,
corresponding
to the Pavlovian
differentiation
task, in which the electric
726
STEFAN
BRUTKOWSKI
V&me
45
shock is associated with the presentation
of CS1 but is not associated
with the presentation
of C&
These experiments
suggest that it is the nature of the testing procedure
and
not a sensory defect that is correlated
with impairment
of visual, acoustic,
or tactile
discriminations.
This conclusion
is supported
by the recent work of Shustin
(I TO),
Brutkowski
(38), and others.
There is thus no compelling
behavioral
evidence
that the prefrontal
cortex is
im plicated
in the integration
of sensory phenomena.
C. Critique
of Concept of Frontal
Lobe Involvement
in Highest
Psychical
Functions
I> Alterations
of unspeciJied behavioral patterns. In the past many observers found
it difficult
to present an objective
description
of deficits after damage
to the frontal
lobes. They were so impressed
with the progressive
development
of the frontal lobes
in phylogeny
that they often a priori
regarded
the prefrontal
areas as the seat of
the highest mental
functions,
despite the fact that they found and described
rather
specific disorders
of somatic and autonomic
origin.
There is good reason to believe
that many early and some current
evaluations
of experimental
data have been influenced
by such preconceptions.
It is also possible that some of the abnormalities
in motor and sensory activities
were attributed
to supposed abnormalities
in psychic
faculties.
Statements
and conclusions
in the literature
confirm
these assumptions.
Thus, Hitzig
(89) wrote in 1874: “Anatomically,
the development
of the prefrontal
lobes coincides
with that of the intellect,
being less in the cat than in the dog, and
still more so in the monkey.”
Ferrier
(62) found that the prefrontal
cortex is a
motor center for contralateral
head and eye movement
and attributed
to the prefrontal
areas inhibitory
functions
influencing
the motor
zones. Nevertheless,
the
author
considered
the prefrontal
lobes to be the center for “attention,”
and this
conclusion
was apparently
stated to emphasize
the relation
of the prefrontal
area
to higher
psychic capacities.
Bianchi
(24, 25), applying
a similar
analysis to his
experimental
material,
inferred
that the removal
of frontal
lobes “disaggregates
the personality.”
He defined the behavioral
changes after operations
on dogs and
monkeys
in purely mentalistic
and anthropomorphic
terms, employing
such phrases
as “stupid
attitude,”
ccsemi-consciousness,”
cCno gratefulness
to people,”
CCeyes devoid of any flashes of intelligence,”
etc. Similar
descriptions
of results were offered
by Rossolimo
(I 5g), Bekhterev
(2 I ) and others.
As recently
as 1947 Beritov
(23) described
symptoms
after frontal
lobe lesions
anterior
to the cruciate fissure in the cat in terms of an impairment
of ccpsychonervous” process, recognized
by the author as the highest form of neural activity.
A cat
with frontal lobectomy
was unable to find a cup containing
food and could neither
see nor smell it. The suggestion
was made that frontal
lobectomy
resulted
in the
loss of the image, corresponding
to the events in the previous
life of the individual.
Later Bregadze
(3 I ) concurred
in this proposal.
In view of experimental
findings
obtained
during
a 12-year period
of investigating
the behavior
of dogs with frontal lesions, Anokhin
(I o) formulated
a highly
monistic
theory of frontal
lobe function.
Its basic assumption
was that the frontal
October rg 65
FUNCTIONS
OF PREFRONTAL
CORTEX
7’17
cortex is an organ that forms the anatomical
substratum
for discrimination
between
specific and nonspecific
stimulus
inputs.
All the concepts discussed in this section are somewhat
subjective
regardless
of how strongly
the authors’
considerations
are derived
from the analysis of their
experimental
findings.
They all formulate
frontal
lobe function
in terms of a unitary process emphasizing
that but one basic function
is served by the frontal areas,
since one basic deterioration
in behavior
follows a frontal
lesion. In this respect
they all are in obvious conflict
with the anatomical
and behavioral
evidence
indicating
the multiplicity
of the structural
and functional
organization
of the prefrontal
area.
2) Dejcit
in memory. More than 30 years ago Jacobsen
(92) showed that monkeys deprived
of the prefrontal
areas lost their ability
to find a food reward that
had been placed in their full view under one of two inverted
cups. Normal
animals
bilateral
lesions of the precould respond after a delay as long as 2 min. However,
frontal areas, unlike those of other cortical
areas, resulted in abolition
of the ability
to perform
a delayed
response. The subjects failed in this test with delays as short
the experiments
showed that acquisition
of the delayed
reas I or 2 sec. Moreover,
sponse habit was affected.
Recently
,Eawicka
and Konorski
(104, 105, I I 4, I I 7)
have demonstrated
that dogs with frontal
lobectomies
are severely impaired
in delayed responses. Also, squirrel
monkeys
with frontal
lesions show a very poor performance
(I 29). On the other hand, lesions of the frontal
lobes in chimpanzees
only a short-lasting
or comparatively
slight
(164) and cats (I I 5, I 89, I go) produce
impairment.
There is total or near-total
sparing of delayed response in infant rhesus
monkeys
after extensive
bilateral
extirpation
of the dorsolateral
prefrontal
cortex
and complete
aspiration
of the sulcus principalis
at 5 and 150 days of age, respectively (84).
Since Jacobsen’s
pioneering
work, the frontal
areas have been recognized
as
the neural substrate for delayed
response behavior,
the deficit in delayed
response
performance
in animals
with frontal
lesions being initially
referred
to as a loss in
immediate
memory
(92). Later investigators
found, however,
that animals
improve
in delayed response problems
after prolonged
testing, food deprivation,
administration of barbiturates
and other pharmacological
agents, temporary
exposure to cold,
or changes in certain
testing procedures
(63, I 05, I 24, I 41, I 48). In view of these
results and those of a number
of other experimental
studies over the past few years,
the postulation
of a loss of immediate
memory
to account for delayed
response impairment
has become untenable
(33, 83, 105, I I 5, I 16, I 29, I 33, I 56, I 74).
D. Hypoactivity
and Hypoemotionality
Loss of Spontaneity or Initiative)
It has long been recognized
rodents (rabbits),
lesions of the
ity. Animals
become apathetic
interest
in their surroundings.
blink in response to threat. Cats
(ccStu~orous~~ Behavior,
Nutism,
that in chimpanzees,
monkeys,
carnivores,
and
frontal
areas may occasionally
result in hypoactivand somnolent
(sometimes
lethargic)
and take less
They walk slowly, bump
into objects and do not
and dogs with frontal
lesions often search for dark
728
STEFAN
BRUTKOWSKI
Volume 45
places and spend hours standing
motionless
with head drooped
or huddle
themselves in a corner; they may raise the head when noise is made, look around,
and
then relapse in the previous
position.
They often push the head against solid objects (e.g., a wall). Sometimes
they attempt
obstinately
to slip or pass under small
pieces of furniture
such as chairs or stools.
Although
states of hypoactivity
have not often been described
after frontal
lobe removal,
in certain preparations
they occur at early postoperative
stages consistently.
In monkeys
they are related to lesions of the rostra1 portion
of areas 6, 7,
and 8 (I oo), and in dogs they are evidently
due to the damage
to the precruciate
fields on the medial
aspect of the hemisphere
(I 80), corresponding
to the premotor
regions.
Isolated
observations
on monkeys
(24) and cats (19, g8), in which the
frontal
lesion was intended
for the area of the corpus callosum
and the anterior
portion
of the cingulate
gyrus, indicate
that a “remarkable
plasticity”
and variety
of cataleptic
symptoms
occur. However,
as far as Kennard’s
cats are concerned,
it
appears from her illustration
that the lesion was, in fact, placed
in the splenial
gyrus and that it slightly
damaged
the posterior
cingulate
gyrus.
E. Hyperactivity
Hyperactivity
has been seen in many frontal
preparations,
including
adult
thus far no increase
rhesus monkeys
(over 2 years old), dogs, and rodents. However,
in activity
has been reported
in chimpanzees
(I I I), squirrel
monkeys
(I 2g), or
lesions. Neither
is there an indication
that
cats (105, I I 5, I I 7, I 89) with frontal
~-year-old
rhesus monkeys
that have undergone
frontal
extirpation
become hyperactive (84). Dogs with lesions anterior
to the presylvian
sulcus are not hyperactive
.
(47)
Hyperactivity
often follows hypoactivity.
It is usually
maximal
in the early
postoperative
period,
and it then tends to decrease.
Sometimes,
it may take the
form of bursts-that
is, it may be interrupted
by intervals
of decreased
activity.
Hyperactivity
is discussed under five headings.
Although
in many frontal preparations
the various
manifestations
of hyperactivity
seem to merge into one, it is
possible to distinguish
all of the following
phenomena
in some instances.
indicate
that hyperactivity
in animals
with
r) State of unrest. Most investigators
frontal
lesions is primarily
related
to locomotion.
Its basic feature is aimless and
seemingly
interminable
pacing or walking.
The animals
move constantly
back and
forth while on the floor (monkeys,
carnivores)
and up and down while on perches
(monkeys).
Movements
are purposeless
and repetitive,
although
not necessarily
perseverative.
They are reminiscent
of the incessant
pacing
of a caged lion and
“beyond
that ever seen in the normal
animal”
(100). According
to French
(66),
increased locomotor
activity
differs from animal
to animal
and is dependent
on the
familiarity
of the animal
with the experimental
situation.
2) Mouvement
de man>ge and stereotyped gross motor behavior. In many instances,
ablation
of frontal areas causes a marked
perseveration
of movement.
Stereotyped,
rhythmic,
alternating
stepping
or rotatory
locomotion
[“forced
circling”
according
to Kennard
and Ectors (gg)] toward
the side of the lesion is seen in unilaterally
ablated
animals,
or, toward either the left or the right side in bilaterally
ablated
Otto ber rg 65
FUNCTIONS
OF PREFRONTAL
CORTEX
729
3) Distractibility
(“inattention”).
This is one of the most striking
symptoms
of
frontal
ablation;
it denotes an abnormal
degree of “turning”
from one activity
to another.
The typical
case of distractibility
in a monkey
with frontal
lesions was
first described
by Kluver
(I o I). When the animal
was offered a grape while eating
one, he dropped
the first grape and took the second until the floor was covered with
the dropped
fruit, but no single grape had been eaten.
4) Hyperactivity
of longstanding
habits (release of resfionses). Definite
evidence
of
such impairment
has been offered by a few investigators.
Thus Afanasev
(5) noted
that dogs with prefrontal
lobectomies
repeatedly
approached
the food cup after
the termination
of the act of eating.
Similarly,
chewing
and licking
movements
were observed over a long period of time after cessation of food intake in rats with
frontal lesions (I 57).
The behavior
of frontally
lobectomized
dogs on acoustic discrimination
under
conditions
of food reinforcement
on either of the two opposite
sides of the experithe animals
were
mental
platform
may be cited (IO, I I, I 69). Preoperatively,
trained to remain
in the middle
part of the platform
by repressing
their spontaneous
activity.
The essential requirement
of the testing procedure
was to approach
the
appropriate
food cup indicated
by one of two acoustic stimuli
presented
in random
succession. Bilateral
extirpation
of frontal
areas 6-8 caused continuous
“pendular”
runs from one food cup to the other throughout
the entire testing period, independent of the stimuli
presented.
(Control
lesions of other cortical
areas produced
no
such behavior.)
However,
when the frontally
lobectomized
dog obtained
food reinforcement
on one side of the platform
only, no cCpendular”
movement
occurred.
In discussing
the implications
of this experiment
Anokhin
(IO) states that a
frontal lesion results in a total disintegration
of motor performance
and a regression
to an early behavioral
pattern
of spontaneous
activity
determined
by the complex
of environmental
stimulation.
(I 70) has brought
forward
evidence
indicating
that
More recently,
Shustin
in dogs with frontal
lobe damage
the previously
trained
motor
CR’s are often replaced by a variety
of motor
unconditioned
reflexes (UR’s).
Workers
in our laboratory
have observed
the following
behavior.
Dogs are
preoperatively
trained
to place the right forelimb
on the food tray on presentation
of a CS in a conditioned-reflex
room. After operation
to induce large frontal lesions
involving
the precruciate
area, the dogs execute the CR continuously,
even in the
absence of CS presentations,
climb up the food tray with both forelimbs,
and gnaw
at the empty food cup. Presumably
a release mechanism
accounts for these motor
manifestations,
since they all were clearly observable
in the preliminary
period of
testing. It is most likely that animals
with frontal
lesions show an increased
tendency to execute movements
deeply rooted early in life or in the early period of preoperative
training,
which subsequently
became
suppressed
while a specific motor
response was being established.
In other words, our conclusion
is that ablation
of
the frontal
lobe is associated
with withdrawal
of inhibition
over certain
motor reactions, a view in general agreement
with Stanley
and Jaynes’
(I 77) notion
of the
impairment
of act inhibition
in animals
with frontal lesions. It is worthwhile
mentioning
that, in many of our preparations,
the overactivity
described
ceded by akinetic
stupor and absence of conditioned
reflex activity.
here was pre-
STEFAN
730
BRUTKOWSKI
Volume 45
5) Hyperactivity
of newZy acquired habits. Brutkowski
(unpublished
Ph.D. thesis) described
a frontal
dog, retested on a previously
acquired
salivary
CR, that
developed
two patterns
of movement
spontaneously
without
any obvious
stimulation. Prior to operation
the dog secreted saliva and exhibited
a food-oriented
reaction in response to the presentation
of either of two CS’i used. After bilateral
prefrontal lobectomy
involving
the precruciate
area, he shook his head to one CS and
climbed
up the food tray to the other CS. Despite extended
postoperative
training
and massive barbiturate
and bromide
administration
the two responses, which had
been evoked by irrelevant
aspects of the experimental
situation,
showed no tendency to diminish.
The enhanced
tendency
to repeat habits may occur in animals
with frontal
lesions that fail to show increased
locomotor
activity.
Following
Pavlov’s
terminolof the excitatory
process” ; Mishkin
ogy, Konorski
(103) referred to it as “inertia
(133) called it “an inability
to suppress whatever
responses normally
prevail
in
the given situation.”
This suggests that once a motor
behavior
pattern
has been
initiated,
it gets stuck and persists indefinitely,
being continuously
executed
or
perseverated
in spite of the absence of the stimulus
originally
responsible.
However,
new adaptations
are possible.
It has been found that the predominating
activity
depends on environmental
conditions
and may shift from one type to another
under
strong stimuli.
It then becomes
apparent
that increased
activity
in animals
with
frontal
lobe ablations
may take different
forms and that periods
of overactivity
may alternate
with periods of relatively
low level of activity.
Moreoever,
Konorski’s
hypothesis
implies
that overactivity
may be induced
in a hypomotile
animal
with
frontal
lesions. In short, to characterize
the overactivity
of animals
with frontal
lobe ablations
one must try to interrelate
the hypo- and the hypermotile
states.
Finally,
the hypothesis
postulated
that increased
locomotor
behavior
is merely
a
reflection
of the animal’s
tendency
to perseverate
motor acts.
Due to the fact that there is a swing from low motor activity
to high activity,
and that stuporous
behavior
occurs alternately
with excitement
in some subjects,
Konorski’s
notion
may be extended
by assuming
that the symptom
of inertia
in
frontally
damaged
animals
pertains
to the inhibitory
as well as to the excitatory
process, even though
the inertia
of excitatory
process often prevails.
Accordingly,
the apathetic
state and ccloss of initiative”
may be considered
a perseveration
of
nonactivity.
F. LOCUS of Dejcit
Rejecting
Hype-
and Hyperactivity
States
Since both hypo- and hyperactivity
often occur in the same frontal
preparation, it is possible that they are the result of one lesion. Indeed,
Konorski
and his
colleagues
(103, I 79) correlate
both states in the dog with lesions of the precruciate
area (anterior
sigmoid
gyrus), particularly
the medial
sector. This deserves emphasis in connection
with the suggestion
by Kennard
and Ectors (gg) that both
“stuporous”
behavior
and the forced circling
movements
in the monkey
result
from one visual defect, viz., head and eye deviation
due to damage
to the frontal
eyefields,
including
area 8 and parts of the adjacent
cortex located
dorsally
and
ventrally.
Stimulation
of the region comprising
the posterior
portion
of area 8 and
October
1965
FUNCTIONS
OF PREFRONTAL
CORTEX
73
I
the anterior
part of area 6 is known to elicit adversive
or orientational
movements
of the head, i.e., turning
of the head and eyes to the opposite
side with rotation
of
(22,
81, 87, 88).
the trunk in the same direction
Since the studies of Jacobsen
(g2), it has been known
that hyperactivity
is
g-12
of
associated
with
ablation
of the dorsolateral
frontal
cortex
(areas
Brodmann).
Most recently
Gross and Weiskrantz
(78, 80) reported
that lesions
situated
within
the sulcus principalis
produce
changes in locomotor
activity
similar to those seen after lesions of the entire dorsolateral
frontal
cortex. However,
Kennard
et al. (I oo), Ruth
and Shenkin
(I 65), and others point out that the removal
of the orbital
cortex may also be effective.
These authors
have presented
evidence
indicating
that lesions of the posterior
orbital
surface (area I 3) produce
maximurn
hyperactivity;
when area 13 is spared no hyperactivity
occurs. On the
other hand, according
to the work of Richter
and Hawkes
(157), Mettler
and
(126),
and Davis (57) it is likely
that when hyperactivity
is present the
Mettler
frontal
lobectomy
has involved
the rostra1 portion
of the caudate
nucleus.
Also
(185) suggest that the damage
to the
Ward (188), Glees et al. (74), and Turner
caudate is crucial since it is generally
impossible
to spare this nucleus while ablating
in the rat is in
area I 3. However,
Beach (20) found that a lesion of the striatum
itself without
consistent
effect on running
behavior.
G. Hyperreactiuity
Motor
activity
in frontal
animals
is increased
on stimuli
such as noise, the
sight of food or threatening
objects, whereas it stops in the darkness,
after enucleation of the eyes, or ablation
of the occipital
cortex (57, 66, 67, x00). Moreover,
the
increased
activity
is positively
correlated
with stimulus
intensity
(g I). Gross and
Weiskrantz
(78, 80) found that after lesions of the lateral frontal
cortex activity
in
light and darkness increases to a familiar
acoustic stimulus
and decreases to novel
acoustic and tactile
stimuli.
Isaac and De Vito (91) suggest that the increase in
motor activity
in response to variations
in illumination
and sound may reflect the
removal
of regulating
influences from the prefrontal
cortex to the reticular
activating system.
To sum up, it becomes apparent
that animals
with frontal lesions are hyperreactive to certain
types of stimuli
rather
than being simply
hyperactive.
This inference is supported
by the following
experimental
work.
r) Impairment
of act inhibition.
Brush et al. (33) have recently
found that monkeys with frontal lesions show abnormal
difficulty
in reversing
stimulus
preferences
or aversions;
this was clearly demonstrated
in a visual discrimination
learning
experiment.
Rhesus monkeys
were trained
in a modified
Wisconsin
General
Testing
Apparatus
on a series of I I -trial object discriminations
presented
at the rate of 3
problems/day
under two different
conditions
of testing. In the ‘cbaited”
condition,
the choice of one object of the pair on the 1st trial was always associated
with a
reward, and on the remaining
IO trials the animals were required
to choose the same
object. Conversely,
in the CCunbaited”
condition
the choice of an object of the pair
in the I st trial was never associated
with a reward,
and on the succeeding
IO trials
the animals
were required
to choose the other object. Although
no impairment
oc-
732
STEFAN
BRUTKOWSKI
Volume 45
curred in the “baited”
condition,
the frontal monkeys
were found to perform
poorly
in the “unbaited”
condition.
On the assumption
that the object choices on the
first trials were determined
by aversions
and preferences
for one object over the
other, the poor performance
in the “unbaited”
condition
was ascribed to the frontal
animals’
great persistence
or inertia
of their initial
sets. It has thus been suggested
that animals
with frontal ablations
have difficulty
in inhibiting
any strong tendency
resulting
from training
or preference,
thereby
perseverating
one response to the exclusion of others. It has furthermore
been suggested
that the impairment
in performance
of these animals
on a variety
of tests, from differentiation
to delayed
response, is likewise related to this deficit (I 8, I 33). Briefly, it has been hypothetized
that a decreased
ability
to suppress the existing
preferences
and aversions,
or the
loss of inhibition
of competing
response tendencies,
is the basic impairment
produced by frontal lobe damge (18, 33,45,
I 33). This conclusion
is in agreement
with
the previously
discussed notion
of the loss of the act inhibition
(I 77) and that of
inertia
of the excitatory
process (103) in animals
with frontal
lesions.
Initially
the response perseveration
hypothesis
was developed
to account
for
the deficit in monkeys
with lateral
frontal
lesions. However,
recent evidence
has
suggested
that monkeys
with orbital
frontal
lesions show similar
but even more
severe impairment
than monkeys
with lateral
frontal
lesions (I 33). Accordingly,
Mishkin
has come to the conclusion
that the perseveration
theory applies even more
appropriately
to the deficits in animals
with orbital
frontal
lesions.
Studies of the sequelae of partial
lesions in the dog have shown that the perseveration
of response is produced
by lesions of the dorsolateral
portion
of the prefrontal cortex but not by lesions of any other parts of the prefrontal
cortex (38-41).
This was demonstrated
in a conditioning
experiment
in which both positive
and
inhibitory
trials were presented
on a schedule having
either IS-set or I-min
intertrial intervals.
After lesions of the dorsolateral
prefrontal
cortex, an impairment
occurred
only in the short-interval
schedule.
It was suggested that this impairment
reflected
response perseveration
and that it was the short intervals
that made it
possible for the perseveration
to occur.
It has long been known that the inability
to shift from one response to another
(perseveration)
is noted in normal
subjects under certain conditions.
Although
the
available
data do not permit
more than the speculation
that perseveration
increases
as one descends the phylogenetic
scale, ,Eukaszewska’s
studies (I 20) have furnished
valuable
evidence
of the remarkable
perseverative
tendency
in normal
rats. aukaszewska believes that this is due to the fact that this species possesses little prefrontal
cortex. It has been found that a long period
of training
is often necessary before
the perseveration
diminishes.
It is worth emphasizing,
however,
that it can diminish. This suggests that the frontal
areas in the rat, like those in other species, exert
a suppressing
action on the mechanisms
concerned
with the expression of perseveration. In support of this thesis, Eukaszewska
(I 2 I) found that when the anterior
tip
of the forebrain
was removed
bilaterally,
a permanent
perseveration
followed.
The evidence
suggesting
a relationship
between the impairment
of differentiation tasks and delayed
response tasks (18, I 33) indicates
that these two defects result from disruption
of a single mechanism.
Against
this conclusion,
however,
are
the findings
that monkeys
with lateral frontal
lesions are less successful than mon-
October 1965
FUNCTIONS
OF PREFRONTAL
CORTEX
733
keys with orbital
lesions in delayed
alternation,
but are better than the monkeys
with orbital
lesions in differentiation,
which suggests a dissociation
of the defects
(45). These conflicting
views await further
experimental
analysis.
Nevertheless,
from all of these studies indicating
an impairment
on both delay type and nondelay
type of problems
there has been a growing
conviction
that the deficit following
a
lesion of the frontal
cortex is not primarily
dependent
on the temporal
aspects of
the spaced problems,
contrary
to the opinion
that since Jacobsen
(92) has been
postulated
by numerous
investigators
to be the primary
effect of such lesions. This
newer concept is in accord with Mishkin
and Pribram’s
(I 35, I 36, I 51) suggestion
that spatial aspects are not critical
in determining
the deficit of animals
with frontal
lesions in delayed
response and delayed
alternation
performance.
However,
it is
worth mentioning
that on the basis of the results obtained
in a spatial-reversal
experiment
Mishkin
(I 33) has recently
suggested that lateral
frontal
lesions do produce
a defect specifically
related
to a spatial factor.
Shustin
(I 70) relates the delayed
response deficit to the impairment
of trace
CR performance,
that is, to a task considered
to be a form of inhibition.
Konorski
and Lawicka
(105) have recently
analyzed
the delayed
response
deficit in dogs and cats with frontal
lesions and concluded
that “the increase of
reflexogenic
strength of the external
stimuli
is the chief factor disturbing
the delayed
response performance.”
In support
of this assumption
the authors found that animals with frontal
lesions are more “stimulus
bound”
than normal
animals.
In
harmony
with other investigators,
Konorski
and Lawicka
have indicated
that animals with frontal lesions do show an increased
perseveration
of response. However,
perseveration
has not been considered
a primary
defect but a consequence
of an
adjustment
of the animal
to the situation
in which an unsolvable
task is presented.
The authors believe that the delayed
response type of test may be looked on as a
task the frontally
lesioned
animal
is unable
to cope with. This interpretation
is in
keeping
with the interpretation
given by Pribram
and his associates
(I 49, I 56),
who indicated
that animals
with frontal
lesions show a progressively
greater defect
as the stimulus-response-reward
contingencies
are made more and more unreliable.
Focal stimulation
and ablation
studies have demarcated
a restricted
prefrontal
area concerned
with delayed response types of functions.
In the monkey,
the critical
lesion producing
the deficit has been delimited
to the midlateral
region
(i.e., the
cortex in and around
the sulcus principalis)
as opposed
to the dorsolateral
and
all other association
cortex and
ventrolateral
regions (26, I 32). Lesions in virtually
the amygdala
have been reported
to produce
no impairment
(162). There are indications
that the localization
is also remarkably
precise in dogs; a small lesion of
the caudal
portion
of the medial
subdivision
of the gyrus proreus
was found to
disturb the performance
(Lawicka,
Mishkin,
Kreiner,
and Brutkowski,
unpublished
data). It is thus likely that the gyrus proreus in the dog is homologous
to the cortex
of the sulcus principalis
in the monkey.
In recent years the effect on delayed
response performance
of destroying
subcortical
and limbic
structures
connected
with the prefrontal
cortex has received
growing
attention.
Here it is of considerable
interest that the role of the medialis
dorsalis nucleus of the thalamus
is not as important
as the anatomical
evidence
would seem to indicate,
for massive lesions in this nucleus are not followed
by a
734
STEFAN
BRUTKOWSKI
Volume 45
delayed
response deficit
(52, I 47). One possible explanation
of these negative
results is that the lesions, involving
both the magnocellular
and parvocellular
portions, damage
two systems that act in opposite directions.
Thus it would be interesting to study the effect of much more circumscribed
lesions. However,
Schulman
(cf. 162) states that total destruction
of the nucleus does produce
an impairment.
There is clear indication,
on the other hand, that the caudate
nucleus is indeed implicated
in mediation
of the delayed
response functions.
Rosvold
and
(160) have shown that either
stimulations
or lesions of the head of the
Delgado
caudate
nucleus interfere
with performance
on delayed
alternation.
A deficit
in
delayed
response performance
after damage
to this nucleus has also been demonthe effects of caudate
lesions are qualitatively
similar
strated (I 7, 163). Generally,
to those of frontal
lesions but they are quantitatively
less severe. The quantitative
difference
may be attributed,
however,
to the fact that the lesions in the caudate
nucleus are often only partial
lesions while those of the frontal cortex are complete.
Recently,
Adey et al. (3) reported
that the subthalamic
zones are essential for
delayed
response performance.
Somewhat
conflicting
results have been obtained
after hippocampus
ablations,
some investigators
reporting
an impairment
of both delayed
alternation
and delayed response performance,
others reporting
impairment
only of delayed
alternathat the
tion (95, I 31, I 34, 142, I 56). More recent work (cf. 162) has indicated
extent of the lesion appears to be important.
Thus, when the amount
of damage
to the hippocampus
is increased,
the impairment
of delayed
alternation
is also increased. Likewise,
the location
of the lesion within
the hippocampus
seems to be a
critical
factor in determining
the effect on delayed
response performance.
Rosvold
(162) noted that the deficit
appears to be greater with anterior
and Szwarcbart
than with posterior
lesions and greater with lesions in regions CA1 and CA3 than
in regions CA2 and CA4 (CA designations
are the hippocampal
regions of Lorente
de No). Also, transection
of the fornix in the dog has been found to be effective
(Dabrowska,
unpublished
data).
It is thus evident that the prefrontal
(dorsolateral
part)-caudate-subthalamichippocampal
complex
is a major part of the neural substrate for delayed
response
and delayed
alternation
behavior.
2) Augmentation
of orienting reflex. Interesting
information
is offered by the study
of CR’s in dogs with lesions of the precruciate
areas (I 78), identified
as part of the
premotor
cortex. Pronounced
reactivity
in the form of an excessive orienting
reflex
to the presentation
of an acoustic CS was described.
Normal
dogs were trained
to
approach
the food box opposite
the starting
place whenever
the CS was presented
I .5 m to the right
or to the left of the food box. Each run to
from speakers situated
the food box in response to the CS was followed
by food reinforcement.
In the
early stages of preliminary
training,
the normal
animal
oriented
its head toward
the CS whenever
the CS was on, and then it ran to the food box and received
an
immediate
or, in another
variation,
a delayed
food reinforcement.
In later stages
of training,
the orienting
reflex was inhibited,
and the animal
approached
the food
box immediately
after the CS presentation.
After lesions of the precruciate
areas
on the medial
aspect of the hemisphere,
the dogs approached
the speaker, looked
October 1965
FUNCTIONS
OF PREFRONTAL
CORTEX
735
at it
This
ance
tion
fixedly, and sometimes
remained
for a period of I o set or more in this position.
abnormal
reactivity
toward the CS, recognized
as an example
of a reappearof the primitive
stage of the orienting
reflex, was strikingly
resistant to extincdespite lack of reinforcement.
Brady and Nauta
(30) made a similar
observation
in rats in which the septal
areas were damaged,
and they designated
the reaction
a “magnet
response.”
In an attempt
to analyze
the remarkable
orienting
reflex in dogs with precruciate
lesions, Konorski
(I 05) suggested that the frontal
cortex, particularly
its
premotor
sector, serves “to inhibit
the orienting
reaction
in order to allow attention
to be shifted, to be decreased
or increased,
depending
on the significance
of the
stimulus.”
Once the frontal cortex is ablated
the primitive
mechanism
of attention
or the orienting
reflex is allowed full sway.
It was also found that when two CS’i were located
one on either side of the
food box, one of them positive
(i.e., associated
with food reinforcement)
and the
other inhibitory
(i.e., not associated
with food reinforcement),
the dog with precruciate
lesions showed an excessive orienting
reflex to the positive
CS but not to
the inhibitory
CS. This suggests that increased
reactivity
to the CS presentation
may be interpreted
in terms of an augmentation
of emotional
reactivity
to stimuli
that precede reinforcement.
In other words, increases in emotional
states and in
drive mechanisms
may determine
the augmented
reactivity
of animals
with frontal
lesions to sensory stimuli.
3) Drive disinhibition.
In view of the assumption
that emotions
and drives play
a decisive role in determining
the degree of reactivity
in frontal animals,
studies of
the effect of frontal lesions in dogs trained
in situations
involving
drive for food and
water or noxious stimulation
are now considered
(I 2, 34-39, 46, 47, 107, 108, I I 3,
1949 195)*
Testing
was carried out on mongrel
male dogs in a Pavlovian
frame mounted
within a soundproofed
conditioned
reflex room. Classical
(type I) and instrumental (type II) procedures
were used. Acoustic,
visual,
and tactile
signals served as
CS’i, which were presented
randomly
in a successive order on a variable
interval
schedule.
positive CS’i caused salivary
Using CR’s based on food or water reinforcement,
outflow
and/or
one of three motor
reactions:
I) active placing
of the forefoot
on
2) placing
of the hindfoot
on an elethe food tray situated
in front of the animal,
vated board in the back, and 3) barking.
Foot-placing
responses were established
according
to the method
of Konorski
and Miller
(106) by passive movements.
Conditioning
of the barking
response involved
the elicitation
first of emotional
barking.
Classical defensive CR’s consisted of either I) flexing of the forefoot reinforced
by an electric
shock administered
through
a bracelet
attached
to the foot, or 2)
salivary outflow reinforced
by the introduction
of weak lactic acid into the mouth.
Respiratory
and licking
movements
were also noted.
In subsequent
training,
inhibitory
CR’s were established
by withholding
reinforcement.
Three inhibitory
tasks were used. I) Simple differentiation
was based
on inhibition
of the reflexes in response to presentation
of the differential
CS. 2)
STEFAN
736
BRUTK-OWSKI
Volume 45
Conditioned
inhibition
involved
a combination
of two successively
presented
signals, viz., the conditioned
inhibitor
(CT), which was an extra stimulus,
and the
positive
CS; a few seconds interval
was interposed
between the components
of the
CI-CS
compound.
The CI-CS
compound
was not reinforced
and resulted
in inhibition.
3) Alternation
was a task in which a CS was presented
in alternate
association with the US; consequently,
the CR was alternately
conditioned
and inhibited.
After bilateral
prefrontal
lobectomy
anterior
to the presylvian
and genual
sulci on the lateral
and medial
aspects, respectively,
of the hemisphere,
the previously inhibitory
CR’s became
disinhibited;
that is, the inhibitory
CS’i elicited
a
positive
CR. In addition,
reactivity
to emotional
and sensory cues increased
considerably
despite the apparent
absence of overactivity
in gross behavior.
Thus it
was found that: a) the amplitude
of the CR on positive
trials was magnified
and
the latency
shortened,
b) there was an excess in salivation
and instrumental
reactivity between trials, c) the UR’s became amplified,
d) the amplitude
and frequency
of respiration
was augmented,
and e) there was a marked
elevation
of food-directed
activities
characterized
by abnormal
sniffing and searching
behavior
in the food
situation
or by an increase
in general
aspects of defensive-aggressive
behavior
in
the situation
in which noxious
stimulation
was used. Bilateral
control
lesions of
central portions
of the parietal
cortex, including
parts of the ectolateral,
entolateral,
and suprasplenial
gyri, did not produce
such a1terations.l
It was noticed
that on occasion,
in spite of an obvious excitement
both to the
positive
CS’i and the stimulus
aspects of the testing situation,
the inhibitory
trials
remained
unaffected.
Because of this, the disinhibition
of previously
inhibitory
CR’s in prefrontal
animals
was considered
secondary
to the increased
reactivity.
It is of interest that postoperative
alterations
of motor,
autonomic,
and affective behavior
patterns often were not observed until after a few daysof postoperative
testing had been completed.2
This was interpreted
to indicate
that before the overreactivity
occurs, the CR must first be strongly reconditioned
with food or noxious
reinforcements.
That animals
with prefrontal
lesions become
clearly hyperreactive
to unconditioned
stimuli,
in that they show an excessive degree of excitation
in the presence
of food or noxious stimulation,
suggests that an increase in a variety
of drive functions accounts for the impairment
of inhibition.
The results also suggest that it is
the emotional
hyperexcitation
and
tivity
that is responsible
for the
behavior.
In view of the close anatomical
not
simply
postoperative
association
the frontal cortex and the hypothalamus
that the hyperreactivity
in animals
with
general
responsiveness
alterations
between
in
CR’s
the mediobasal
or hyperacand
gross
parts
of
and limbic
system, it may be hypothesized
frontal lesions is due to disruption
of hypo-
October rg 65
FUNCTIONS
OF PREFRONTAL
CORTEX
737
the hypothalamus
could result in the release of drive functions
from cortical
inhibitory
control.
The core of the hypothesis,
then, is that increased
reactivity
to
emotional
stimuli
causes difficulty
with suppression
of the CR on inhibitory
trials
and results in disinhibition.
There is now adequate
experimental
evidence
that the medial
frontal
cortex
in lower mammals
is intimately
related
to hypothalamic
mechanisms
and that a
close parallel
exists between the changes of drive functions
in animals
with lesions
of the hypothalamus
and the changes in those with lesions of the medial
frontal
cortex. Recent findings
on rabbits by Balinska
et al. (I 5, 16) demonstrate
that after
damage
to the medial
hypothalamus
there is a disinhibition
of instrumental
food
CR’s to inhibitory
CS’i in conjection
with hyperphagia.
Similarly,
a disinhibition
accompanied
by an increased
searching
for food follows lesions of the frontal
cortex on the medial
aspect of the hemisphere.
Animals
with lesions of the medial
hypothalamus
and those with lesions of the medial
frontal
cortex, involving
parts
of the premotor
areas, show a remarkable
similarity
in other aspects of behavior
as well. During
conditioning
sessions, both groups eat hurriedly
but clumsily,
spilling the food, and very often do not finish eating the portions
offered but instead
demand
new portions
by scratching.
Furthermore,
both animals
with medial
hypothalamic
lesions and those with lesions involving
or restricted
to the medial
premotor cortex gnaw at the food cup and other objects within their reach. While
the
CS is being presented,
these animals
execute not only the previously
acquired
right
forefoot reaction
but also a response with the left forefoot,
or, alternately,
they step
on the food tray with both forefeet simultaneously.
When
not reinforced,
these
newly acquired
movements
develop
into scratching.
Then,
during
intertrial
intervals the animals
raise their forefeet alternately
but refrain from placing
them on
the food tray. The instrumental
CR is violent
and, at the same time, disorderly
and
clumsy compared
to the precision
with which it was performed
prior to surgery.
Recent evidence
(15) indicates
that rabbits
with lesions of the lateral
hypothalamus,
exhibiting
a depression
both in CR activity
and food intake in the initial
postoperative
period,
will show after recovery
[made possible by administration
of
subcutaneous
isotonic saline injection
(I 4)] a conspicuous
impairment
of inhibition
in association
with an increased
interest for food. It is worth mentioning
that in
the early postoperative
stages, rabbits
with lesions of medial
frontal
cortex, like
those with the lesions of the lateral
hypothalamus,
show a reduced
reactivity
and
food intake and are clearly apathetic.
Similarly,
dogs with lesions of the premotor
area anterior
to the cruciate
sulcus
on the medial
surface of the hemisphere
(with or without
additional
medial
prefrontal lesion) show a depression
of food intake and body weight in association
with
an impairment
in instrumental
CR activity
(38, 39, 47, I 79, I 80). In the early
postoperative
stages, dogs with lesions of medial
premotor
cortex are often somnolent. However,
the drowsiness is usually seen when the animal
is left alone. When
approached,
it becomes livelier
and if food is offered it starts eating. It then shows
an increased
and prolonged
interest in food accompanied
by aggressive manifestaThis observation
suggests that
tions, which gives an impression
of voraciousness.
the disturbance
caused by lesions of the prefrontal-premotor
areas concerns
the
initiation
of the act of eating as well as the mechanism
responsible
for the cessation
738
STEFAN
BRUTKOWSKI
Volume 45
of eating. Generally,
dogs with lesions of the premotor
area recover their previous
feeding habits and weight within
a few days; they then become
hyperreactive
to
the CS presentations
and disinhibited
on inhibitory
trials.
On the other hand, dogs and rabbits with lesions of the lateral frontal cortex,
or those in which the lesion on the medial
surface is confined
solely to the prefrontal
area, show neither
a deficit in feeding nor in responsiveness
(38, 40, I 83; Balinska
and Brutkowski,
unpublished
data).
To recapitulate,
lesions restricted
to the prefrontal
area on the medial
aspect
of the brain are followed
by a phase of increased
reactivity
in association
with the
disinhibition
syndrome
without
any signs of a decreased responsiveness
in the initial
postoperative
period.
On the other hand, large lesions of the medial
prefrontal-premotor
cortex or those involving
solely the medial
premotor
cortex appear to be
correlated
with two phases in the pattern
of behavior;
the phase of apathy, lack of
spontaneity,
and reduced
reactivity
is followed
by one of increased
reactivity
and
disinhibition,
reflecting
the behavioral
alterations
resulting
from lesions of the
lateral
hypothalamus
as well as those of the medial
hypothalamus.
These physiological
observations
are in consonance
with the anatomical
evidence, indicating
an anatomical
association
between the prefrontal
cortex and the
lateral
and medial
hypothalamic
regions.
Further
evidence
for the involvement
of medial
frontal
cortex in mechanisms
of drive inhibition
in subprimates
follows from the recent work by Brutkowski
and
preopMempel
(42) and Brutkowski
and Dabrowska
(40, 41). Dogs were trained
eratively
in both positive
and inhibitory
CR’s on a schedule
of I-min
intertrial
intervals.
After lesions had been made in the dorsal subdivision
of the medial
surface of the prefrontal
cortex (with or without
the germal area), errors of disinhibition occurred
in association
with an increase in food-directed
behavior.
In contrast,
lesions of the ventral
subdivision
of the medial
prefrontal
cortex, or those of the
dorsolateral
prefrontal
cortex, produced
neither
the disinhibition
syndrome
nor an
increase in food-directed
activity.
Szwejkowska
et al. (I 83), using a slightly
different testing procedure,
obtained
identical
results.
precruciate
According
to Stepien
and her colleagues
(I 79, 180), the medial
area in the dog is likewise
necessary for the maintenance
of the food inhibitory
CR%.
From these observations
the conclusion
may be drawn that in the dog drive
inhibition
is a function
of both the prefrontal
and premotor
cortex on the medial
aspect of the hemisphere.
(41, 182)
Recent reports suggest that the dorsomedial
nucleus of the thalamus
and the basolateral
portion
of the amygdaloid
complex
(41, 43, 68) are essential
components
of the drive inhibition
mechanism.
Ablation
of either of these structures
leads to a disinhibition
remarkably
similar
to that following
damage
to the anteromedial
prefrontal
cortex.
There
thus appears
to be considerable
evidence
that, in subprimates,
the
complex
composed
of the medial
prefrontal-premotor
cortex,
the dorsomedial
nucleus of the thalamus,
the medial
and lateral hypothalamus,
and the basolateral
division
of the amygdala,
constitute
a neural substrate,
or part of one, for the type
of inhibition
referred
to as “drive
inhibition.”
Moreover,
this evidence
and also
October 1965
FUNCTIONS
OF PREFRONTAL
CORTEX
739
that pointing
to a neural substrate
concerned
with delayed
response types of functions are in accord with the anatomical
findings
described
in an earlier
section of
this paper, suggesting
the existence
of two prefrontal-limbic-subcortical
systems,
each involving
a different
behavioral
mechanism.
Recently
an attempt
was made to indicate
in the monkey
the focal frontal area
concerned
with inhibition
of drives and food-motivated
behavior
(45, 49). Rhesus
monkeys
were trained
preoperatively
in either a visual pattern
differentiation
(“go
-no
go”) task or on conditioning
and extinction
of a food-rewarded
response. After selective ablations
of frontal
cortex, monkeys
with lesions of the orbital
areas,
unlike those with lesions of the dorsolateral
areas, showed an impairment
of inhibition by exhibiting
difficulty
in withholding
responses on inhibitory
(“no go”) trials
or by a very slow rate of extinction.
Accordingly,
the orbital
frontal
cortex was
identified
as responsible
for the impairment
of inhibitory
performance.
It was also
suggested that the orbital
frontal
cortex in the monkey
and the anteromedial
prefrontal cortex in the dog may be functional
homologues.
Moreover,
in view of these
findings
and those previously
obtained
on dogs the deficit in inhibition
in monkeys
with orbital
frontal
lesions could be interpreted
in terms of disinhibition
in the
motivational-emotional
sphere (45).
H. Changes in Afective
Behavior
After
Frontal
Lesions
Emotional
changes resulting
from frontal
lobe ablations
have been reported
by several investigators.
Fulton et al. (7 I) showed that after extensive frontal damage in the monkey
“an increase in appetite
occurs which sometimes
involves ingestion of two to three times the normal
amount
of food.”
Watts and Fulton
(192)
found that bilateral
partial
or complete
ablation
of the frontal lobes caused morbid
(165) found only a
hunger,
and, occasionally,
intussusception.
Ruth
and Shenkin
whereas
slight increase in food intake
after removal
of areas 13 in the monkey,
lesions of the frontal
poles
Langworthy
and Richter
(I I I) showed that “bilateral
was also confirmed
in dogs with premade cats ravenous
for food.” This finding
that frontal lobe
frontal-premotor
ablations
(5, 50, I 70). Anand et al. (9) reported
lesions including
or restricted
to the posterior
orbital
cortex in monkeys
and cats
produced
a decrease in food intake, whereas those that spared the posterior
orbital
cortex were followed by an increased food intake. As mentioned
above, our findings
indicate
that lesions involving
all the medial
prefrontal-premotor
cortex anterior
to the cruciate
fissure in the dog produce
a temporary
drop in food intake,
while
those confined
to the prefrontal
cortex leave food intake unchanged
(39, 41).
Also, changes in behavior
associated with anger and aggressiveness
have been
(188), Glees et al. (74), and Kennard
reported
after frontal
lobe damage.
Ward
(98) noted diminution
of preoperative
irritability
and aggressiveness
in cingulectomized
cats and monkeys.
This is at variance,
however,
with another
group of
observations
indicating
that cingulectomized
animals
develop
more aggressiveness
and Inand angry behavior
immediately
after operation
(98, I 30, I 46). Fulton
graham
(70) described
a marked
reaction
of rage in previously
friendly
and playful
cats after bilateral
lesions of the prechiasmal
area (corresponding
to area 14),
whereas Kennard
(97) demonstrated
rage responses after entire removal
of the
740
STEFAN
BRUTKOWSKI
Volume 45
frontal
poles or, in some instances,
after selective ablation
of the orbital
cortex.
These findings
have been confirmed
by Bond et al. (27) on cats, as well as by
Aleksandrov
(7) and Bykov (50) on dogs with damage
to the prefrontal-premotor
areas. Brutkowski
et al. (42,44)
have recently made an effort toward outlining
precisely the frontal area focally involved
in suppression
of the rage reaction
in the dog.
They demonstrated
that a lesion rostra1 to the genu of the corpus callosum
and extending
over small portions
of the genual,
subgenual,
and subproreal
regions results in an apparent
savageness and violent
aggressive-defensive
reactivity
in the
presence of man. The authors
also attempted
an analysis of the rage behavior
in
animals
with frontal lesions and concluded
that it largely reflects changes in somatosensory processes -specifically,
hypersensitivity
to tactile
stimulation.
This inference is in line with an earlier observation
by Babkin
(I 3) pointing
out a dramatic
increase in sensitivity
of the skin in association
with rage in dogs with frontal lesions.
on the erect hair in the monkey
with a lesion of
Smith
(I 7 I) found that blowing
the rostra1 cingulate
cortex ‘Ccauses vigorous
startle reaction
as if there is an increased sensitivity
to this type of stimulus.”
Finally,
it was found (44) that not only
touching
but approaching
the dog with lesions of the genual cortex elicits a marked
rage reaction.
Similar
observations
have been made on rabbits with lesions on the
medial
surface of the frontal
cortex (Brutkowski
and Wojtczak-Jaroszowa,
unpublished data).
Whatever
the mechanism,
there appears little doubt that damage to the frontal
cortex is followed
by an augmentation
of various emotional
states combined
with
increased
reactivity
to external
stimuli.
In support
of this thesis a further
observation from our laboratory
may be mentioned
(38). In an attempt
to use a reinforcement unrelated
to food or defensive
behavior
the dog was trained
to lift its forefoot
to the presentation
of an acoustic CS, and each lifting response was associated with
stroking
of the head. After prefrontal
lobectomy
an increase in overt sexual behavior occurred.
Thus it was noticed
that both the CS presentations
and strokings consistently
elicited
penile erection
and copulatory
movements.
The differential
responsiveness
of a normal
and a frontally
damaged
animal
to the stimulus
might
depend on differencies
in threshold.
There can be little doubt that stroking
and the
preceding
CS, which may be considered
subthreshold
for overt sexual behavior
patterns
even though
they may produce
a number
of responses indicating
a considerable
degree of pleasure,
become
effective
in eliciting
sexual excitation
after
frontal
ablation,
as a result of the hypersensitivity
to mild stimulation.
I. Impairment
of CR Performance
The relatively
little experimental
evidence available
on the release of emotions
in animals
with damage
to the frontal
lobes may be understood
as resulting
from
a lack of relevant
evaluative
procedures.
Again, it may also be due to misinterpretation of some experimental
findings.
Recently
several authors
have reported
that
is based on
frontal lobe damage
reduces fear (I I 8, I 52, I 81, I g I ). This conclusion
the finding
of postoperative
impairment
of the avoidance
reflex. Yet, neither avoidance nor other instrumental
techniques
can be used as unambiguous
indicators
of
changes in emotional
behavior.
Experimental
data on dogs and monkeys
(5, 36,
FUNCTIONS
October zg65
OF
PREFRONTAL
CORTEX
74
I
38, 46, 47, 49, I 70) demonstrate
that after frontal
lesions a generalized
depression
of instrumental
performance
often occurs. This is a reflection
of the hypoactive
state that is, at times, noticed
immediately
after surgery (particularly
after lesions
damaging
parts of the premotor
or orbital
areas). However,
in the dog the salivary
CR preceding
food or acid reinforcement
is regularly
present during
the first postoperative
testing; in addition,
there is often increased
feeding or aversive behavior.
It seems reasonable
to assume, therefore,
that abolition
or rapid extinction
of the
instrumental
CR may be caused by strong emotions
that are released from cortical
inhibition.
It is thus possible that, in the early postoperative
stages, a new type of
behavior
is created, as a result either of increased
anxiety
under avoidance
conditions, (e.g., a rapid circling
in the safe compartment
or intensified
freezing response
in the shuttle-box
situation)
or of increased
searching
in the food situation,
and
that this new behavior
is in conflict with the instrumental
performance.
According
to this view, elimination
of the instrumental
CR is largely the result of a revival of
numerous
elementary
forms of behavior,
and thus need not indicate
a diminution
of emotionality.
III.
CONCLUSIONS
Analysis
of behavioral
changes in animals
with frontal lesions reveals that the
prefrontal
cortex is essential for important
inhibitory
capacities.
Thus, ablation
of
prefrontal
cortex is associated
with removal
of inhibition
and with regression
to
primitive
forms of motor and motivational
behavior
patterns.
Loss of inhibition
of
competing
response tendencies
(response
perseveration)
and impairment
of inhibition referred to as “drive
disinhibition”
may reflect the relation
of the prefrontal
cortex to limbic-subcortical
structures
via the caudate-subthalamic-hippocampal
complex
and the hypothalamic-amygdaloid
complex,
respectively.
The author expresses his gratitude to Jerzy Monorski,
Waclawa
Lawicka,
Mortimer
Mishkin, H. Enger Rosvold, and Irena Stepieh for their critical reading, valuable discussion,
and
helpful evaluation of this manuscript.
REFERENCES
I.
2.
ADEY,
campal
rabbit.
ADEY,
study
W. R. An
connections
experimental
of the
study
cingulate
Brain
74: 233-247,
1957.
W. R., AND
M. MEYER.
of hippocampal
afferent
of the
cortex
An
pathways
hippoin the
experimental
from
ior and correlated
hippocampal
and subcortical
slowwave
activity.
Arch. New-ok
6 : x94-207,
1962.
4. ADRIANOV,
0. S. Sur les liaisons
et les fonctions
des noyaux
thalamiques
du systkme
“non
spCcifique.”
Acta Neural.
Psychiat.
Be&. 60 : 704-722,
1960.
5. AFANASEV,
N. I. Experimental
findings
concerning
frontal
lobe
functions.
(Doctor’s
thesis.)
St. Peters-
Granular
Cortex
and
Behavior,
edited
of frontal
In : The
by J. M.
cortex
Frontal
Warren
K.
Akert.
New
1964, chap.
18,
7. ALEKSANDROV,
tween
the cerebral
pp.
Zap.
Leningr.
(Russian)
ALLEN,
W.
hippocampi,
Gor.
pre-
frontal
and cingulate
areas
in the monkey.
J. Anat.
(London)
86 : 58-74,
I 952.
3, ADEY,
W. R., D. 0. WALTER,
AND
D. F. LINDSLEY.
Subthalamic
lesions.
Effects
on learned
behav-
burg,
r g 13. (Russian)
6. AKERT,
K. Comparative
anatomy
and
thalamofrontal
connections.
and
8.
York:
Peda.
IO.
I I.
Inst.
1940*
B. K.,
Book
83:
F. Effect
of ablating
and
occipito-parieto-temporal
ing pyriform
areas)
olfactory
conditioned
754-771,
g. ANAND,
McGraw-Hill
Co,
372-396.
I. S. On the
relationships
cortex
and the diencephalon.
lobes
on
reflexes.
S.
DUA,
beUch.
141-230,
the
1949.
frontal
lobes,
(except-
positive
and
negative
Am. J. Physiol,
128:
AND
G.
S.
CHHINA.
Higher
nervous
control
over
food
intake.
Indian
J.
Med. Res. 46 : 277-287,
1958.
ANOKHIN,
P. K. Nodal
questions
in investigating
the higher
nervous
activity.
In: Problemy
Vysshei Nerunoi Deiatelnosti.
MOSCOW:
Izdat.
AMN
pp. g-1 20.
(Russian)
ANOKHIN,
P. K. A new conception
logical
architecture
of conditioned
SSSR,
of the
reflex.
1949,
physiolIn:
Brain
STEFAN
742
Mechanisms
and Learning.
Publ.,
1961,
pp.
I 89-229.
12.
AULEYTNER,
of bilateral
(type
I)
Oxford
: Blackwell
14.
16.
20
the
Effects
classical
and
some
behaviour
in dogs.
: 243-262,
1960.
the physiology
Voenno-Med.
Akad.
1963.
on
A. ROMANIUK,
effect
of lesions
internal
reflexes
inhibition
type
II.
I 961.
21 : 189-197,
of the
in
the
Biol.
Acta
18.
19.
KIN.
Comparison
of the effects
of frontal
and caudate
lesions
on discrimination
learning
in monkeys.
J.
Comfy Physiol.
Psychol.
55 : 458-463,
I 962.
BARRIS,
R. W. Cataleptic
symptoms
following
bilateral
cortical
2 13-220,
BEACH,
activity
21.
22.
24.
25.
28.
29.
30.
3 I.
in
Effects
of brain
V.
cats.
Am.
J.
lesions
rat.
J. Camp.
M.
Foundation
Physiol.
upon
Psychol.
of oculomotor
‘938.
BERITOV,
Psychonervous
nerve.
running
of the Science
of the Frontal
Lobes.
New
39.
of the
the
frontal
York:
W.
and the FuncM,
Wood
and
1922.
BLUM,
granular
R. A.
cortex
A. M. A. Arch.
BOND,
D, D.,
V. ROWLAND.
Effects
of subtotal
lesions
on delayed
reaction
in
44.
of frontal
monkeys.
terior
thalamic
lesions
in the cat. A. M. A. Arch.
rol. Psychiat.
78: 143-162,
1957.
BONIN,
G. VON. The frontal
lobe of primates:
Neucyto-
architectural
studies.
Res. Pubt.
Assoc. Nervous
Mental
Diseases
27 : 67-83,
1948.
AND
P. BAILEY.
The Neocortex
of
BONIN,
G. VON,
Macaca
mutatta.
Urbana,
Ill. : Univ.
of Illinois
Press,
1947.
BRADY,
mechanisms
following
J. V., AND W.
in emotional
septal
forebrain
Camp. Physiol.
BREGADZE,
45.
46.
47.
1953.
of the
cat
with
an
Ergebnisse
Lokalisation
Beriicksichtigung
8 : 241-
iiber
die verder Grosshirndes Stirn-
Physiol.
Psychol.
54 : 3 19-325,
I 961.
S. The
effect
of prefrontal
lobecconditioned
reflexes
in dogs.
Acta
of classical
reflexes
and infollowing
Acta
Biof.
Exfitl.,
Polish
Acad.
Sci.
1 g : 301-3
I 2,
1959.
BRUTKOWSKI,
hibition.
In:
S. Prefrontal
The Frontal
Granular
edited
by J.
McGraw-Hill
BRUTKOWSKI,
the so-called
M. Warren
and K. Akert.
New
York:
Book Co., 1964, chap.
12,pp.
242-270.
S. On the functional
properties
of
“silent”
areas
of the frontal
cortex
in
cortex
and drive
inCortex
and Behavior,
In: Funktsii
Lobnykh
dolei
Mozga.
Moscow:
Izdat.
(Russian)
Bolshikh
Moskovsk.
Polusharii
Univ.,
S., AND J. DABROWSKA.
prefrontal
lesions
as a function
intervals.
Stience r 3g : 505-506,
Disinof duraI 963.
S., AND
J. DABROWSKA.
The
of the cortico-subcortical
structures
in
of food motor
conditioned
reflexes.
In:
Mekhanizmy
Dvigatelnoi
Tsentrafnye
i Perifericheskie
Deiateinosti
Zhivotnykh
i Chelowka.
Moscow:
Izdat.
AN
SSSR,
in press.
(Russian)
BRUTKOWSKI,
S., AND E. MEMPEL.
Disinhibition
of inhibitory
conditioned
responses
following
selective
brain
1961.
BRUTKOWSKI,
PEL.
Alimentary
lesions
in dogs.
Science
I 34 : 2040-2041,
S., E. FONBERG,
type II (instrumental)
reflexes
in amygdala
dogs.
Acta
Acad. Sci. 20 : 263-271,
1960.
BRUTKOWSKI,
S., E. FONBERG,
AND
Biof.
E. MEMconditioned
Exptt.,
AND
Polish
E. MEM-
Angry
behavior
in dogs following
bilateral
lein the genual
portion
of the rostra1
cingulate
Acta Biot.
Exptl.,
Polish
Acad. Sci. 2 I : 199-205,
1961.
BRUTKOWSKI,
ROSVOLD.
monkeys
after
S.,
Positive
ablation
M.
MISHKIN,
AND
and
inhibitory
motor
of orbital
or dorsolateral
face
of the frontal
cortex.
In: Central
Mechanisms
of Motor
Functions.
Prague
Sci. Publ.
House,
1963,
pp. 133-141.
J. H. NAUTA.
Subcortical
behavior:
affective
changes
lesions
in the albino
rat. J.
Psycho/.
46 : 339-345,
A. N. The behavior
Fiziol.
bilateral
prefrontal
lobectomies
in dogs.
Acta
Biol.
Exptl.,
Polish
Acad. Sci. I g : 291-299,
I 959.
BRUTKOWSKI,
S. The
solution
of a difficult
inhibitory
task (alternation)
by normal
and prefrontal
PEL.
sions
gyrus.
Neural.
Psychiat.
67 : 375-386,
1952.
C. T. RANDT,
T. G. BIDDER,
AND
Posterior
septal,
fornical
and
an-
Neue
Acad. Sci. Ig: 281-289,
1959.
BRUTKOWSKI,
S. Comparison
strumental
alimentary
conditioned
BRUTKOWSKI,
participatian
the inhibition
lobes.
TY. Inst.
Biol.
ExptZ.,
Polish
Acad. Sci. I 7 : 327-337,
I 957.
BRUTKOWSKI,
S. Effects
of prefrontal
ablations
on salivation
during
the alimentary
unconditioned
reflex
and after
its cessation.
Acta Biol.
Exptl.,
Polish
41.
43,
of the Brain
lesions.
J. Camp.
BRUTKOWSKI,
tomies
on salivary
BRUTKOWSKI,
hibition
after
tion of intertrial
42.
lobes.
K.
histologische
besonderer
40,
I : I 44-151,
frontal
(Russian)
hirns.
Anat.
Anz. 41: 157-216,
1912.
BRUSH,
E. S., M. MISHKIN,
AND
H. E. ROSVOLD.
Effects
of object
preferences
and aversions
on
discrimination
learning
in
monkeys
with
frontal
animals.
Golovnogo
in press.
78,
I. S. On the Basic Forms of the Nervous
and
Activities.
Moscow-Leningrad
: Izdat.
of
38.
of the
276, I 950.
BRODMANN,
gleichende
rinde
mit
dogs.
7. (Russian)
Functional
after
sec-
J. Neurophysiol.
AN SSSR,
1947.
(Russian)
BIANCHI,
L. The
functions
Brain
I 8 : 497-530,
1895.
BIANCHI,
L. The Mechanism
37.
I Ig :
31 : I 45-r
Brain Functions.
St. Petersburg,
1907, vol.
BENDER,
M. B., AND
J. F. FULTON.
recovery
in ocular
muscles
of a chimpanzee
co.,
27.
lesions
male
‘941*
BEKHTEREV,
tion
26.
r 937.
F. A.
in the
tion
23.
34.
36.
BATTIG,
K.,
H. E. ROSVOLD,
AND
M. MISHKIN.
Comparison
of the effects
of frontal
and caudate
lesions
on delayed
response
and alternation
in monkeys. J. Corn& Physiol.
Psychol.
53 : 400-404,
1960.
BATTIG,
K,,
H. E. ROSVOLD,
AND
M. MISH-
20.
33.
BALINSKA,
H,
AND S. BRUTKOWSKI.
Extinction
of food-reinforced
responses
after
medial
or
lateral
hypothalamic
lesions.
Acta Biol.
Exptl.,
Polish
medial
hypothalamus
alimentary
conditioned
Exptt.
Polish
Acad. Sci.
17.
32.
35.
Acad.
Sci. 24: 213-217,
1964.
BALINSKA,
I-I., K. LEWINSKA,
AND W. WYRWICKA.
The
Volume 45
excision
Sept.-Oct.,
I gog. (Russian)
BALINSKA,
H. Food
intake
and type
II conditioning in lateral
hypothalamic
rabbits
survived
under
forced
hydration.
Acta Bioi.
Exptl.,
Polish
Acad. Sci. 23:
115-1?4,
15.
Scientific
B., AND S. BRUTKOWSKI.
prefrontal
lobectomy
on
defensive
conditioned
reflexes
other
responses
related
to defensive
Acta Biol.
Exptl.,
Polish
Acad. Sti.
I 3. BABKIN,
B. P. Findings
concerning
of frontal
lobes
in the dog.
Zzv.
BRUTKOWSKI
H.
CRs
E.
in
sur-
and Peri$heral
: Czech.
Acad.
BRUTKOWSKI,
S.
J. KONORSKI,
W.
LAWICKA,
I. STQPIEN,
AND
L. STEPIEN.
The Eflect
on Motor
Conditioned
Rejexes
of Frontal
Lobe Lesions
in
the Dog. Xddi:
Xddz.
Tow.
Nauk.
PWN,
Wydz.
III,
I 955.
(Polish)
BRUTKOWSKI,
S.
WICKA,
I. ST&PIEN,
J.
AND
KONORSKI,
L. STEPIEN.
W.
The
LAeffect
October
FUNCTIONS
196”
of the removal
of frontal
on motor
conditioned
48.
49.
BUTTER,
VOLD.
rewarded
C. M.,
Conditioning
response
in
M.
MISHKIN,
AND
and
extinction
after selective
ablations
rhesus
monkeys.
510
1963*
BYKOV,
gans. New
CAMPBELL,
52.
tion of
Press,
r 905.
CHOW,
K.
53*
destruction
of some
A. M. A. Arch, Neural.
CLARK,
W. E. LE
54*
Exptl.
7:
frontal
CLARK,
tomical
and
Lack
of behavioral
thalamic
Psychiat.
GROS.
effects
lobes
of the brain.
Lancet 254 : 353-356,
I 948.
W. E. LE GROS,
AND M. MEYER.
Anarelationships
between
the
cerebral
cortex
&it.
Med.
Bull.
6: 341-345,
the hypothalamus.
57.
frontal
rats. Acta BioZ. Exptl.,
Polish
Acad. Sci. 24:
102, 1964.
DAVIS,
G. D. Caudate
lesions
and spontaneous
59.
60.
61.
62.
63.
64.
65.
rophysiol.
I I : 39-55,
I 948.
DEMIDOV,
V. A. Conditioned
dogs
without
anterior
halves
(salivary)
both
281, 1960.
FERRIER,
D. Functions
and Elder,
I 886.
FINAN,
J. L. Delayed
furcement
in monkeys
of the Brain,
reinfrontal
lobes.
Am. J. Psychol.
55 : 202-2
I 4, 1942.
FRANZ,
S. I. On the functions
of the cerebrum:
The frontal
lobes
in relation
to the production
retention
Physiol.
FRENCH,
of simple
sensory-motor
8: 1-22,
1902.
G. M. Spatial
discontiguity
lesions
of
the
G. M.
The Frontal
Hill
and
Co.,
FRENCH,
reaction
decrement
monkeys.
J. Camp.
J.
PRIBRAM.
havior
L.,
The
in the
frontal
Science
K.
dog
and
Akert.
chap.
AND
and
76.
770
New
790
80.
4, pp.
in
normal
81.
and
E.
effect
of lesions
on affective
of the
AND
839
728-
and
cognitive
pyriform-amygdala-
K.
J.
by
G.,
pp. 74-101.
GRijNBAUM,
Observation
AND
between
on
be-
Physio-
cortico-subcortical
J. Neurophysiol.
M.
WHITTY,
7:
AND
H.
Physiol.
L.
Psychol.
WEISKRANTZ.
impairment
56 : 41-47,
Evidence
auditory
dis-
on
response
in frontal
1962.
L.
WEISKRANTZ.
monkeys.
Some
85.
A. S. F. AND
the physiology
C. S. SHERRINGTON.
of the cerebral
cortex
of the anthropoid
apes. Proc. Roy. Sot. London,
Ser. B
72: 152-155,
1903.
HARLOW,
H. F., AND J. DAGNON.
Problem
solution
by monkeys
following
bilateral
removal
of prefrontal
areas.
I. Discrimination
and
discrimination
problems.
H.
J.
F.,
AND
Exptl.
Psychol.
32 : 351-356,
P. SETTLAGE.
areas upon
PubZ. Assoc.
learning
Nervous
Effect
of ex-
performance
Mental
Diseases
27 : d+-cigs
1948HARLOW,
H.
F.,
K.
AKERT,
AND
K.
A.
SCHILTZ.
The effects
of bilateral
prefrontal
lesions
on learned
behavior
of neonatal,
infant
and preadolescent
monkeys.
In:
The Frontal
Granular
Cortex
and
Behavior,
edited
York:
McGraw-Hill
I 26-148.
H.
C. W.
Camp.
tirpation
of frontal
of monkeys.
Res.
I, I 955.
Verte-
S. McCULLOCH.
of some
chimpanzee.
crimination
and delayed
Exptl.
Neural.
5 : 453-476,
GROSS,
C. G., AND
J.
Locomotor
ROSVOLD,
in
Shkola,”
Arch. Ges. Physiol
26: r-29,
1881.
F. uber
die Verrichtungen
des GrossArch. Ges. Physiol.
34 : 45 I-505,
I 884.
F. uber
die Verrichtungen
des Gross-
monkeys.
19630
GROSS,
C.
for dissociation
* 94O*
HARLOW,
brain-damaged
W.
“Vysshaia
mon-
hirns.
Pfltiger’s
Arch. Ges. Physiol.
42 : 41 g-467,
1888.
GROSS,
C. G. Comparison
of the effects
of partial
and
total
lateral
frontal
lesions
on test performance
reversal
McGraw-
48 : 496-50
AND
Izdat.
19440
P., J. COLE,
hirns.
Pytiger’s
GOLTZ,
H.
hirns.
PLpiger’s
GOLTZ,
H.
I.
56-73.
Psychol.
Gosud.
in
changes
in behavior
produced
by lateral
frontal
l*
sions in the macaque.
In: The Frontal
Granular
Cortex
and Behavior,
edited
by J. M. Warren
and K. Akert.
New
York : McGraw-Hill
Book
Co.,
1964,
chap.
5,
monkeys
edited
York:
base of the brain
(pre-chiasmal).
J. Physiol.
(London)
67 : XXVII-XXVIII,
I 929.
FULTON,
J. F., C. F. JACOBSEN,
AND M.
A.
KENNARD.
A note
concerning
the relation
of the
by
association.
Behavior,
Emotional
of the
75*
and
135:
H. F. HARLOW.
Physiol.
H.
lobes
Cortex
1964,
G. M.,
FULLER,
The
Granular
Warren
Book
in
cortex.
lesions
and
CAIRNS.
The effects
of lesions
in the cingular
gyrus
and adjacent
areas in monkeys.
J. Neural.
Neurosurg.
Psychiat.
I 3: I 78-190,
1950.
GOLTZ,
H. F. uber
die Verrichtungen
des Gross-
82.
Am.
Behavior.
: Chapman
74.
84.
729, 1962.
FRENCH,
M.
frontal
habits.
50:
199-204s
GLEES,
Smith
predelay
of the
and Adjective
73.
reflexesin
hemispheres.
response
with
after
remova
Lobotomy
Psychot.
brates.
Moscow:
I 960. (Russian)
GAROL,
H. W.,
lo-
to
Neu-
London:
Physiol.
72.
78.
(Doctor’s
thesis.)
St. Petersburg,
1 gog. (Russian)
DE VITO,
J. L., AND 0. A. SMITH.
Projections
of
the prefrontal
lobe
in monkey.
Federation
PYOC. 19:
J.
68.
of
Camp.
frontal
lobes
to posture
and forced
grasping
keys. Brain
55 : 524-536,
1932.
GALPERIN,
S. I. Neurohumoral
Regulations
gg-
I 958.
in the
Diseases
27 : 433-437,
1948*
DELGADO,
J. M. R., AND R. B. LIVINGSTON.
Some
respiratory,
vascular,
and thermal
responses
stimulation
of orbital
surface
of frontal
lobe.
J.
In:
67.
learning
in frontal
rats.
Sci. 24: 19-26,
1964.
reversal
learning
in
comotion
in the monkey.
Neurology
8 : I 35-139,
DELGADO,
J. M.
R. Respiratory
centers
frontal
lobe.
Res. PubZ. Assoc. Nervous
Mentai
with
66.
J. R eversal
Polish
Acad.
J. Multiple
J.
logical
neuronography
connections
in the
nuclei.
1954.
of the
56.
58.
7I*
following
association
71 : 762-771,
The connexions
complex.
A Neurophysiological
Analysis.
London
Hall,
Ltd.,
1951.
FULTON,
J. F., AND F. D. INGRAHAM.
disturbances
following
experimental
K. M. The Cerebral
Cortex
and the Internal
OrYork:
Chemical
Publ.
Co., Inc.,
1957.
A. W. Histological
Studies on the LocalisaLondon
: Cambridge
Univ.
Cerebral
Function.
L.
743
89-96,
1957.
FULTON,
J. F. Frontal
65-75,
19500
DbBROWSKA,
Acta BioZ. Exptl.,
DbBROWSKA,
55.
69.
H. E. ROSof a food
of frontal
Neural.
CORTEX
hippocampal
of the cerebral
cortex
in dogs.
Acla
Viol.
Exptl.,
Polish
Acad. Sci. I 7 : I 67-188,
x 956.
BULYGIN,
I. A. Cortical
regulation
of gastric
motility,
and
cortical
reception
of impulses
from
the
stomach
following
ablation
of the premotor
areas.
ByuZ. Eksperim.
Biol.
i med. 2 : 69-84,
I 941. (Russian)
cortex
5o*
poles
reflexes
OF PREFRONTAL
by J. M. Warren
Book
Co.,
and K. Akert.
1964,
chap.
HARMAN,
P. J., M.
TANKARD,
AND F. A. METTLER.
An experimental
analysis
of the topography
and polarity
date-neocortex
interrelationships
in
Anat.
Record
I I 8 : 307-308,
I 954.
M.
New
7, pp.
HOVDE,
anatomical
of the cauthe
primate.
STEFAN
744
86.
HINES,
M.
462-574,
87. HINES
88.
89.
go.
91.
On
localization.
Physiol.
ROD. g :
1929.
M.
Hosp.
M.
Hopkins
HINES,
cerebral
107.
The
“motor”
cortex.
Bull.
Jo/&s
60: 313-336,
1937.
Movements
elicited
from
precentral
gyrus
of adult
wave
currents.
HITZIG,
E.
A. Hirschwald,
2: 197-210,
108.
I
function
in
association
I 3 : 3-60,
I I.
94.
95*
96.
JUNG,
R., AND R. HASSLER.
The
extrapyramidal
motor
system.
In : Handbook
of PhysioZogy.
Washington,
D. C. : Am. Physiol.
Sot.,
vol. II, 1960, pp. 863-928.
KALISCHER,
0. Uber
die Bedeutung
des Stirnteils
I I 2.
des Grosshirns
fur die Fressdressur.
Zentr.
Physiol.
716-718,
1910.
KARMOS,
G., AND E. GRASTYAN.
Influence
hippocampal
lesions
on simple
and
delayed
I 13.
ditioned
1962.
KENNARD,
reflexes.
Acta
M.
ual stimuli
monkeys.
A.
A.
Physiol.
Hung.
Alterations
in
following
lesions
in
M. A. Arch.
Neural.
of
114.
con-
2 I : 215-224,
response
the frontal
Psychiat.
to
vis-
lobes
41 : I I
in
98.
KENNARD,
in the cortex
PathoE. ExptZ.
KENNARD,
cingulate
on behavior
of cats.
159~‘69, 1955.
99
100.
101.
102.
KENNARD,
M.
ECTORS.
117.
Forced
region
of the cerebral
Problems.
Acad.
cortex.
5th
Sci.
USSR,
Symfi.
1939
problem
J, The
Learning.
x961,
Oxford
pp.
test.
In:
Hill
AND
prefrontal
Brain
121.
and
Publ.,
Warren
Book
damentaux
r&flexes
Co.,
W,
XAWICKA.
Granular
and
1964,
J. AND
de la thdorie
conditionnels
on
122.
Ltd.
Cortex
K. Akert.
chap.
Analysis
the
and Behavior,
13, pp.
S. MILLER.
physiologique
moteurs.
York:
I
edited
23.
McGraw-
27x-294.
Les @i&es
des mouvements
Warszaw-Lw6w
lobec-
in
effects
dogs.
reactions
in
1g : 22 1-231,
of prefrontal
ablations
dcta BioZ. Exptl.,
Polish
W.,
AND
lobectomies
Acta
BioZ.
LAWICKA,
ties of delayed
Exptl.,
J.
on delayed
Acad. Sci.
dogs. Acta
1957.
The physioIII.
The
KONORSKI.
on the delayed
Polish
Acad.
Sci.
The
effects
responses
2 I : I 41 -I
fon-
I
acquis.
:
W., AND
responses
J. KONORSKI.
The
to double
preparatory
in normal
and
prefrontal
dogs.
Acta
Polish
Acad. Sci. 22 : 126-134,
1962.
XAWICKA,
W.,
AND J. KONORSKI.
of motor
perseveration
after
prefrontal
Fischer,
1907, vol. III.
XUKASZEWSKA,
I.
perseverative
tendency
Peripheral
Mechanisms
Czech.
Acad.
LUKASZEWSKA,
tally
lesioned
in
56,
propersignals
BioZ.
Exptt.,
A symptom
ablations
in
24.
The
return
reaction
in white
rats.
In:
of Motor
Functions.
Publ.
House,
1963.
I. Returning
behavior
in fronrats.
In:
Tsentralnye
i Perifericheskie
application
19549
MACLEAN,
brain”)
in
and the
Central
and
Prague
:
Sci.
Mekhanizmy
Dvigatelnoi
Deiatelnosti
Zhivotnykh
veka. Moscow:
Izdat.
AN SSSR,
in press.
MACLEAN,
P. D. The limbic
system
and
campal
formation:
Studies
in animals
and
sible
of
delayed-response
New
prefrontal
119.
to the
Mechanism
Scientific
animals
The Frontal
06. KONORSKI,
L.es
: Blackwell
J,,
by
by J. M.
approach
In:
of the
effects
of lobotomy
on a feeding
inhibition
in dogs.
J. Camp. Physiol.
Psychol.
43 : 41 g-427,
I 950.
LUCIANI,
L. Physiologic
des Menschen.
Jena:
G.
115-132.
KONORSKI,
errors
physiological
memory.
effect
118.
(Russian)
of recent
The
tomy
on the vocal
conditioned
reflexes
BioZ. Exptl.,
Polish
Acad. Sci. 17: 317-325,
LAWICKA,
W., AND J. KONORSKI.
logical
mechanism
of delayed
reactions.
animals.
In:
Central
and
Pen$herat
Mechanisms
of
Motor
Functions.
Prague:
Czech.
Acad.
Sci.
Publ.
House,
1963, pp. I 23-132.
LICHTENSTEIN,
P. E. Studies
of anxiety.
II. The
120.
KONORSKI,
J. On the
hyperactivity
in animals
following
lesions
of the frontal
lobes.
Probl.
Fisiot.
Tsentr. Nervnoi
Sistemy,
Akad.
Nauk
SSSR,
Inst. Fiziol.
Sb. 1957.
I
L.
the frontal
lobes.
J. Neurophysiol.
4: 512-524,
1941.
KLUVER,
H. Behavior
Mechanisms
in Monkeys.
Chicage:
Univ.
of Chicago
Press,
1933.
KOMENDANTOVA,
A. L. The premotor
cortex
as
104# KONORSKI,
105.
AND
circling
in monkeys
following
lesions
of the frontal
lobes.
J. Neurophysiot.
I : 45-54, I 938.
KENNARD,
M. A., S. SPENCER,
AND G. FOUNTAIN.
Hyperactivity
in monkeys
following
lesions
of
a regulatory
on Physiological
(Russian)
103.
A.,
W.
the
visual
“associative
area”
Psychol.
Monographs
37 : 107-166,
1961.
116.
I8:
J. Neurophysiol.
1948.
XAWICKA,
cats.
M. A. Focal
autonomic
representation
and its relation
to sham
rage.
J. NeuroNeural.
4: 295-304,
1945.
M. A. Effect
of bilateral
ablation
of
area
of destroying
monkey,
Genet.
*959I 15. XAWICKA,
of prefrontal
53-
* I 65, I 939.
970
study
of micturition
released
from cereAm. J. Physiol.
I 15 : 694-700,
I 936.
0. R., AND C. P. RICHTER.
In-
creased
spontaneous
activity
produced
by frontal
lobe
lesions
in cats. Am. J. Physiol.
I 26 : I 58-161,
1939.
LASHLEY,
K. S. The mechanism
of vision:
XVIII.
Effects
of the
24:
S. BRUTKOWSKI,
1-5,
1952.
myeloarchitectonics
of the frontal
Camp. Neural.
I I 6, I I 7-134,
I 961.
0. R., AND F. H. HESSER.
An
experimental
bral control.
LANGWORTHY,
of normal
and prefrontal
Camp. Physiol.
Psychol.
51:
F’ Studies
of cerebral
functions
of the frontal
Camp. Psychol.
Monographs
S. BRUTKOWSKI,
I. STEPIEN.
The effect
of the
fields
of the cerebral
cortex
activity
of animals.
Bull.
Sot.
IIO.
JACOBSEN,
C.
primates:
I The
area in monkeys
with
W. XAWICKA,
AND
removal
of interprojective
on the higher
nervous
stimulation
lobectomized
the activity
monkeys
J.
(Polish
(Polish)
Sci. Let&es.
LGdk 3 :
KREINER,
J. The
cortex
of the dog. J.
LANGWORTHY,
on
1933.
J., L. STEPIEk,
109.
1936.
93.
1952.
KONORSKI,
HORSLEY,
V., AND E. A. SCHAFER.
A record
of
experiments
upon
the functions
of the cerebral
cortex.
Phil.
Trans.
Roy. Sot. London,
Ser. B I 79 : I-45,
1888.
ISAAC,
W., AND J. L. DE VITO.
Effect
of sensory
172-I 74, * 958
92.
Ksiaznica
Atlas
T.N.S.W.,
French
summary)
KONORSKI,
J., L. STEPIE&,
W. XIAWICKA,
AND I. STEPIEN.
The effect
of partial lesions
of the frontal
and parietal
lobes
on motor
conditioned
reflexes.
Neural.
Neurochir.
Psychiat.
Polska
by stimulation
with
sine
3 : 442-466,
I 940.
z&r
das Gehirn.
Berlin:
chimpanzees
J. Neurophysiol.
Untersuchungen
1874.
Volume 45
BRUTKOWSKI
to
P.
relation
the brain
stem.
tional
processes.
MALMO,
R.
D.
man.
J.
Neurosurg.
The
limbic
to central
gray
removal
1942.
its hippotheir
posI I : 29-44,
system
(“visceral
and reticulum
Evidence
of interdependence
Psychosomat.
Med.
I7:
B. Interference
factors
response
in monkeys
after
Neurophysiol.
5 : 295-308,
i CheZo-
(Russian)
of
emo355-366, I 955.
in delayed
of frontal
in
Iobes.
J.
FUNCTIONS
October 1965
I
25.
MARSALA,
the frontal
J.,
cortex
hypothalamus
Czecholou.
I
26,
127.
28.
129.
I. GROFOVA.
the basal
pp.
F.
56-57.
A.,
AND
C.
PREFRONTAL
Connections
ganglia,
thalamus,
In:
State
C.
Thases
Health
of
144.
of the
Publ.
145.
METTLER.
The
effects
of striatal
injury.
Brain
65: 242-255,
1942.
METTLER,
F. A., C. HOVDE,
AND
H. GRUNDFEST.
Electrophysiological
phenomena
evoked
by
electrical
stimulation
of caudate
nucleus.
Federation
PYOC.
I
with
and mesencephalon.
Congr.
Prague:
Med.
House,
x 962,
METTLER,
AND
OF
107,
I I :
ME’M’LER,
TLER,
A.,
J. D.
AND
J. SPINDLER,
COMBS.
Disturbances
C.
C.
in
frontal
cere148.
with
130.
lesions.
In:
The Frontal
Granular
havior,
edited
by J. M. Warren
and
York:
McGraw-Hill
Book
Co., 1964,
MIRSKY,
A. F., H. E. ROSVOLD,
131.
PRIBRAM.
Effect
of cingulectomy
on social
behavior in monkeys.
J. Neurophysiol.
20 : 588-601,
I 957.
MISHKIN,
M. Visual
discrimination
performance
132.
following
Ventral
Psychol.
MISHKIN,
133.
Cortex
Akert.
134*
135.
I
36.
and Behavior,
New
York
I
38.
1399
140.
J.
Neurophysiol.
of central
The Frontal
K.
H. PRIBRAM.
following
partial
I. Ventral
vs. lateral.
Physiol.
Psychol.
47 : I 4-20,
I 954.
MISHKIN,
M., AND
K. H. PRIBRAM.
the effects
of frontal
lesions
in monkeys:
of delayed
alternation.
J. Camp. Physiol.
49: 36-40,
MISHKIN,
delaying
~156.
M.,
reward
response.
J.
Camp.
on
NAUTA,
W. J. H. Anatomical
the amygdaloid
complex,
the
nucleus
and the orbitofrontal
155.
Analysis
of
II. Vari-
the
between
thalamic
monkey.
of the
GranI
141.
chap*
19, PP. 397-4o9*
NISSEN,
H. W,, A. H.
142.
Delayed
chimpanzees.
ORBACH,
response
and
discrimination
learning
J. Camp. Psychol.
26 : 361-386,
1938.
J., B. MILNER,
AND
T. RASMUSSEN.
and
143.
Learning
hippocampal
PAPEZ,
Arch.
J.
Neural.
AND
V.
38:
725-743,
1937.
J. H. MASSERMAN.
J. Nervous
Mental
R.
parts
I 26:
H.,
H.
E.
of
A.
The cingulates
I 26 : 148-152,
Disease
ROSVOLD,
A.
AND
F.
lesions
upon
rhesus
monkey.
1956.
deJ.
PRIBRAM,
K. H. Some
physical
and pharmacological factors
affecting
delayed
response
performance
baboons
following
frontal
lobotomy.
J. Neurophysiol.
of
13: 373-382,
PRIBRAM,
the behavioral
1g50K. H. A further
deficit
that
mate
frontal
PRIBRAM,
the olfactory
cortex.
ExptZ.
Neurot.
3: 432-466,
1961.
K. H., AND
L. KRUGER.
Functions
of
brain.
Ann. N. Y. Acad. Sci. 58: 109-I
38,
19540
PRIBRAM,
the effects
alternation.
PRIBRAM,
K. H.,
of frontal
J. Camp.
K. H.,
experimental
follows
injury
M. MISHKIN.
lesions
in monkey:
Physiol.
Psychol.
49:
AND
L. WEISKRANTZ.
AND
analysis
in the
of
pri-
Analysis
of
III.
Object
41-45,
I 956.
A com-
of the effects
of medial
and lateral
cerebral
on conditioned
avoidance
behavior
in
J. Camp. Physiol.
Psychol.
50: 74-80,
1957.
PRIBRAM,
K. H., K. L. CHOW,
AND
J. SEMMES.
Limit
and
organization
of the cortical
projection
from the medial
thalamic
nucleus
in monkey.
J. Camp.
Neural.
g8 : 433-448,
I 953.
PRIBRAM,
K. H., M. A. LENNOX,
DUNSMORE.
Some
connections
of
fronto-temporal,
limbic
and
hippocampal
Macaca
PRIBRAM,
NORS.
R. H.
orbitoareas
of
AND
the
mulatta.
J. Neurophysiol.
I 3:
127-135,
1950.
K. H., W. A. WILSON,
AND
J. CONEffects
of lesions
of the medial
forebrain
on
alternation
behavior
of rhesus
monkeys.
ExptZ. Neural.
6 : 36-47,
1962.
PRIBRAM,
K. H., A. AHUMADA,
J. HARTOG,
AND
L. ROSS.
A progress
report
on the neurological
158.
Psychiat.
ROSE,
frontal
159.
and
964,
1964, chap.
3,
C. P., AND
activity
and
of the frontal
2:
231-240,
J. E.,
cortex
pp. 28-55.
C. D. HAWKES.
Increased
food intake
produced
in rats
poles of the brain.
J. Neural.
1939.
C.
its
AND
and
dorsal
nucleus
Assoc. Nervous
ROSSOLIMO,
studying
N. WOOLSEY.
connections
with
The
the
orbitomedio-
in rabbit,
sheep
and
cat. Res.
MentaZ
Disease
2 7 : 2 I o-232,
I 948.
I. G. Surgico-toxical
method
brain
functions.
A&h.
Psikhiatr.
1893.
P&Z.
for
(Rus-
sian)
60.
NOWLIS.
ROSVOLD,
effect
by
retention
in monkeys
after
amygdalaresection.
Arch. Neural.
3 : 230-25
I, I 960.
W. A proposed
mechanism
of emotion.
Psychiat.
1958.
PETERS,
Book
Co.,
RICHTER,
spontaneous
by removal
I
RIESEN,
its component
Mental
Disease
40-56,
‘958.
PAVLOV,
I. P. Conditioned
Rq7exes.
An Investigation
the Physiological
Activity
of the Cerebral
Cortex.
London:
Oxford
Univ.
Press,
1927.
PECHTEL,
C., T. McAVOY,
M.
LEVITT,
157*
Ber-
edited
by J. M. Warren
McGraw-Hill
Book
Co.,
brain,
J. Nervous
processes
disturbed
by frontal
lesions
in primates.
In:
The Frontal
Granular
Cortex
and Behavior,
edited
by J.
M. Warren
and K. Akert.
New York:
McGraw-Hill
of
Physiot.
Anat. Record I 36 : 251, I 960.
NAUTA,
W. J. H. Some
efferent
connections
prefrontal
cortex
in the monkey.
In: The Frontal
and Behavior,
New York:
156.
Psychol.
Effects
perform-
relationships
dorsomedial
cortex
in
153.
Analysis
of
I. Variations
Psychol.
48:
Physiol.
J- W. Visceral
connections.
parison
resections
monkeys.
1540
ance in monkeys
with frontal
lesions.
J. Camp.
Psychol.
5 I : 276-28
I,
I 958.
MUNK,
H. ther
die Functionen
der Grosshimrinde.
lin : Hirschwald,
I 890.
ular Cortex
K. Akert.
152.
20:
sets after
Granular
L. WEISKRANTZ.
visual-discrimination
AND
151.
Visual
disablations
J. Camp.
36-40,
19550
MISHKIN,
M., AND
K. H. PRIBRAM.
the effects
of frontal
lesions
in the monkey:
of delayed
149.
150.
edited
by J. M. Warren
and K.
: McGraw-Hill
Book
Co.,
1964,
chap.
I I, pp.
2 I 9-241.
MISHKIN,
M., AND
crimination
performance
of the temporal
lobe:
ations
137.
Cortex
and BeK. Akert.
New
chap.
8.
AND
K. H.
partial
ablations
of the temporal
lobe:
II.
surface
vs. hippocampus.
J. Camp.
Ptrysiol.
47 : 187-193,
1954.
M. Effects
of small
frontal
lesions
on de-
layed
alternation
in monkeys.
615-622,
1957.
MISHKIN,
M. Perseveration
frontal
lesions
in monkeys.
In:
745
MIRSKY.
The
effect
of thalamic
layed
response-type
tests in the
Camp. Physiol.
Psychol.
4g : 96-104,
METgastro-
intestinal
function
after
localized
ablations
of
bral cortex.
Arch. Surg. 32 : 618-623,
1936.
MILES,
R. C. Learning
by squirrel
monkeys
PAPEZ,
and their
KLING,
AND
and behavior.
147.
1952.
F.
146.
CORTEX
H.
of
stimulating
161.
within
the
Camp.
Physiot.
and
J. M.
AND
R.
destroying
frontal
lobes
Psychol.
H.
of frontal
nerformance.
E.,
of
the
AND
M.
on
Brain
brain.
1956.
MISHKIN.
Nmmsory
discrimination
Mechanisms
of
structures
monkey’s
4g : 365-372,
The
performance
electrically
lesions
In:
DELGADO.
test
or
ROSVOLD,
effects
E.,
delayed-alternation
learning
and
k&w
J.
STEFAN
746
Oxford:
162.
Blackwell
555-576.
ROSVOLD,
Scientific
H.
E.,
AND
Neural
structures
involved
formance.
In: The Frontal
edited
by J. M. Warren
163.
McGraw-Hill
ROSVOLD,
SZWARCBART.
monkeys
on
tion
164.
pp.
J. Camp.
Physiol.
Psychol.
SZWARCBART,
The effect
RUCH,
T. C., AND H. A. SHENKIN.
of area 13 on the orbital
surface
of the
to hyperactivity
and
hyperphagia
in
Neurophysiol.
6 : 349-360,
I 943.
Architektonische
des Stirnhirns.
167.
168.
conditioned
reflexes
of both hemispheres.
I g I I. (Russian)
SCOLLO-LAVIZZARI,
169.
tical
area 8 and its thalamic
projection
mulatta.
J. Camp. Neural.
I 2 I : 259-270,
SHUMILINA,
A. I. The functional
N. M.
Further
The
frontal
monkeys.
und
Nervenarzt
G.,
without
thesis.)
AND
K.
172.
173.
174.
cingular
cortex
as revealed
by its responses
to
excitation.
J. Neurophysiol.
8 : 241-255,
I 945.
H.
Ueber
Anatomie,
Entwicklung
und
Neocortex.”
In: L&e
JubiPathologie
des “Basalen
Zaire du Dr. tudo van Bogaert.
Bruxelles
: Acta
Medica
Belgica,
I 962.
STAMM,
J. S. Electrical
stimulation
of frontal
cortex
in monkeys
during
learning
task. J. Neurophysiol.
24: 414-426,
STAMM,
J. S. Retardation
Learning
by stimulation
of frontal
of an alternation
I 961.
and
facilitation
in
cortex
in monkeys.
In : The Frontal
Granular
Cortex
and Behavior,
edited
J. M. Warren
and Akert.
New York:
McGraw-Hill
Book
Co., 1964, chap.
6, pp. I 02-125.
175.
STAMM,
in learning
of monkeys.
176.
STAMM,
J.
epileptogenic
and retention
177.
563, 1960.
STANLEY,
of the frontal
183.
S., AND K. H, PRIBRAM.
lesions
in frontal
cortex
in monkeys.
J. Neurophysiot.
Effects
of
on learning
23: 552-
AND J. JAYNES.
The
Psychol.
Rev. 56 : 18-32,
function
I 949.
BioZ.
Exptl.,
Polish
Acad.
Sci.
23 : 45-59,
J. M.,
elimination
K.
of
AND
SMITH.
conditioned
Frontal
lobotomy
anxiety
in the
amus.
Zh. Vysshei
Nervnoi
Deyatel’nosti
im. I. P. PavZova I 3 : 666-672,
I 963. (Russian)
SZWEJKOWSKA,
G.,
J.
KREINER,
AND
B.
SYCHOWA.
The effect
of partial
lesions
of the prearea
on alimentary
Acta BioZ. Exptl.,
Polish
1963.
TRAVINA,
A.
A.
Efects
conditioned
reflexes
Acad. SC& 23: 181-192,
of Selective
Brain
the Alimentary
and Acid Conditioned
Reflexes.
Ezhegodnik
Inst. Eksp. Med.
AMN
SSSR,
TURNER,
E. A. Cerebral
control
of
Brain
77 : 448-486,
1954.
191.
192.
Thalamus.
on
:
I 88.
rgo.
The Primate
Press,
1938.
E. The
medial
L.esi0n.s
Leningrad
1956.
respiration.
comparative
anatomical,
physiological
and
clinical
study.
J. Camp. Neurot.
73 : 87-115,
I 940,
WARD,
A. A. The cingular
gyrus : Area
24. J. NCUYO-
189.
E.
in
187.
thalamic
Chicago:
nucleus.
physiol.
I I : I 2-23,
1948.
WARREN,
J. M. The
behavior
of carnivores
primates
with
lesions
in the prefrontal
cortex.
The Frontal
Granular
Cortex
and Behavior,
edited
A
and
In:
by
J. M. Warren
and K. Akert
New York:
McGraw-Hill
Book
Co.,
x964, chap.
g, pp. 168-191.
WARREN,
J. M., H. WARREN,
AND
K. AKERT.
Orbitofrontal
cortical
lesions
and
learning
in cats.
J. Camp. Neural.
I 18 : I 7-41,
1962.
WATERHOUSE,
I. K. Effects
of prefrontal
lobotomy on conditioned
fear and food responses
in monkeys. J. Camp. Physiol.
Psychol.
50 : 81-88,
I 957.
WATTS,
J. W., AND J. F. FULTON.
Intussusception
-the
relation
of the
cerebral
cortex
to intestinal
motility
in the monkey.
New EngZ. J. Med. 2 IO : 883-
193.
89% 1934.
WHITE,
L. E., W.
Cingulum
fasciculus
I 94.
Exptl.
Neural.
2 : 406-42
I, I 960.
WOLF,
K. Effect
of prefrontal
lobectomy
conditioned
reflex
performance
in dogs.
195.
W. C.,
cortex.
Acta
AND J. KREINER.
The
ablation
of the premotor
conditioned
reflexes
in
WALKER,
A.
Univ.
of Chicago
WALKER,
A.
by
J. S., AND W. A. MAHONEY.
Facilitation
by electrical
excitation
of frontal
cortex
Federation
Proc.
21 : 358, I 962.
of
rat. J. Corn&
Physiol.
Psychol.
48 : I 26-129,
1955.
SYRENSKII,
V. I. Alternations
of the higher
nervous
activity
following
injury
of medial
nuclei
of the thal-
186.
rostra1
electrical
SPAT&
studies
182.
185.
I 71.
Further
181.
Cor-
627. (Russian)
SHUSTIN,
N. A. Physiology
of Frontal
Lobes. An Experimental
Investigation.
Leningrad
: Medgiz.
(Russian)
SMITH,
W. K. The
functional
significance
of the
STEPIEN.
1963.
STREB,
and
the
184.
areas of the cerebral
COI tex
in the conditioned-reflex
activity
of the dog. In: Problemy
Vysshei Nervnoi
Deiatelnosti.
Moscow
: Izdat.
AMN
SSSR,
I 949, pp. 561170,
dogs.
frontal
dogs.
in Macaca
I 963.
role
of frontal
L.
STEPIEN,
I., L. STEPIEN,
effects
of total
and partial
cortex
on the instrumental
of salivary
AKERT.
AND
180.
J.
anterior
halves
St. Petersburg,
I.,
STEPIEN,
I., L. STEPIEN,
AND J. KONORSKI.
The effect
of bilateral
lesions
in the premotor
cortex
on type
II conditioned
reflexes
in dogs.
Actu BioZ.
ExptZ.,
PtZish Acad. Sci. 20:,225-241,
1960.
lobes
funktionelle
34 : I 5g-
investigation
in dog
(Doctor’s
relation
STEPIEN,
179.
A. F.
of frontalin
Volume 45
the functional
organization
of the premotor
cortex
in
dogs.
In:
Tsentralnye
i Perifericheskie
Mekhanizmy
Dvigatelnoi
Deiatelnosti
Zhivotnykh
i Cheloveka.
Moscow
:
Izdat.
AN SSSR,
in press.
(Russian)
51 : 437-
on delayed
response
performance
J. Comfi. Physiol.
Psycho/.
54: 368-374,
F.
I 78.
SZWARCBART.
SANIDES,
Differenzierung
168, 1963.
SATURNOV,
I
66.
K.
1961,
in delayed-response
perGranular
Cortex
and Behavior,
and K. Akert.
New
York:
H. E., M. K.
AND M. MISHKIN.
lobe
damage
chimpanzees.
1961.
165.
M.
Ltd.,
Book
Co., 1964, chap.
I, pp. I-I 5.
H.
E., M.
MISHKIN,
AND M.
K.
Effects
of subcortical
lesions
in
visual-discrimination
and single-alterna-
performance.
4449 ‘9580
ROSVOLD,
MIRSKY,
Publ.,
BRUTKOWSKI
M.
NELSON,
study
by
AND L. E. FOLTZ.
evoked
potentials.
on multiple
Bull.
Acad.
9Zon.
Sci., Ser. Sci. Biot.
I 2 : 2 77-2 79, I 964.
ZERNICKI,
B. The
effect
of prefrontal
lobectomy
on water
instrumental
conditioned
reflexes
in dogs.
Acta BioZ. Exptl.,
Polish Acad. Sci. 2 I : 157-162,
1961.