European Journal of Neuroscience, Vol. 18, pp. 2103±2109, 2003
ß Federation of European Neuroscience Societies
REVIEW ARTICLE
Ascending visceral regulation of cortical affective
information processing
Gary G. Berntson,1 Martin Sarter1 and John T. Cacioppo2
1
2
The Ohio State University, 1885 Neil Avenue, Columbus, OH 43210, USA
The University of Chicago, 5848 S. University Avenue, Chicago, IL 60637, USA
Keywords: acetylcholine, amygdala, anxiety, basal forebrain, memory, visceral afference
Abstract
Over a century ago, William James proposed that strong emotions represent the perceptual consequences of somato-visceral
feedback. Although the strong form of this conception is no longer viable, considerable evidence has accumulated indicating a range of
visceral in¯uences on higher neurobehavioural processes. This literature has only recently begun to consolidate, because earlier
reports generally remained at the demonstration level, and pathways and mechanisms for such in¯uences were uncertain. Recently,
speci®c effects of visceral feedback have become apparent on cortical activity, cerebral auditory-evoked responses, anxiety, memory
and behavioural aspects of immunological sickness. Moreover, considerable progress has been made recently in determining the
speci®c neural pathways and systems underlying these actions, especially the role of noradrenergic projections from the nucleus of the
tractus solitarius and the locus coeruleus to the amygdala in memory processes, and to the basal forebrain in the processing of anxietyrelated information. The present paper highlights selected recent ®ndings in this area, and outlines relevant structures and pathways
involved in the ascending visceral in¯uence on higher neurobehavioural processes.
Introduction
Contemporary neurobehavioural models often emphasize top-down
in¯uences from rostral neural systems onto lower effector mechanisms. Since William James (1884) proposed that certain emotions may
represent the perceptual consequence of somatovisceral feedback,
however, there has been also a growing recognition of the importance
of ascending, bottom-up in¯uences on higher neural substrates.
Although variations of the James concept continue to have proponents
(Ekman et al., 1983; Damasio, 2003), neither the original conception
nor these variations are strongly supported by the extant data. Considerable evidence has accumulated, however, indicating a range of
visceral in¯uences on higher neurobehavioural processes (Cameron,
2002; Morris, 2002). This literature has only recently begun to
consolidate, because earlier reports generally remained at the demonstration level, and pathways and mechanisms for such in¯uences were
uncertain. Recently, speci®c effects of visceral feedback have become
apparent on cortical activity (Berntson et al., 2002), cerebral auditoryevoked responses (Berntson et al., 2003), anxiety (Berntson et al.,
1998), memory (Williams & Clayton, 2001; McGaugh, 2002) and the
immunological sickness response (see Romanovsky, 2002; the rest of
the special issue of Autonomic Neuroscience). Moreover, considerable
progress has been made in determining the speci®c neural pathways
and systems underlying these actions, especially the role of the
amygdala and the basal forebrain cortical cholinergic projection in
Correspondence: Dr G. G. Berntson, as above.
E-mail: [email protected]
Received 1 May 2003, revised 13 August 2003, accepted 14 August 2003
doi:10.1046/j.1460-9568.2003.02967.x
mediating the behavioural effects of ascending visceral afferent information.
Bottom-up processing
A substantive literature has elucidated somatic sensory inputs, central
links and descending pathways involved in affective processes (e.g.
Lang et al., 2000; LeDoux, 2000). Less is known of the ascending
visceral modulation of higher neurobehavioural substrates, although
ample pathways exist for such an in¯uence. The nucleus tractus
solitarius (NTS) is the primary visceral relay station in the brainstem
(Fig. 1), which in turn issues direct ascending projections to rostral
structures including the amygdala, the basal forebrain corticopetal
cholinergic system (Semba et al., 1988) and the cortex (Papadopoulos
& Parnavelas, 1991). The NTS also directly and via the nucleus
paragigantocellularis (PGi) can drive ascending noradrenergic projections from the locus coeruleus (LC) to these same rostral areas (AstonJones et al., 1996). The rostral targets of these ascending projections
include forebrain neuronal substrates that have been implicated in
cognitive and emotional processes. The amygdala is a central structure
in neural systems underlying fear and affective processes (Lang et al.,
2000; LeDoux, 2000), and amygdalo-cortical (especially medial prefrontal) circuits have been conceptualized to be involved in guiding
behaviour based on environmental and somatovisceral feedback
(Bechara et al., 2003). Additionally, the basal forebrain cholinergic
system is an important regulator of cerebral cortical function, and has
been implicated in cortical activation, attention and anxiety (Everitt &
Robbins, 1997; Berntson et al., 1998; Sarter et al., 2001b). Because of
the widespread ascending anatomical relations between the basal
2104 G. G. Berntson et al.
Fig. 1. Ascending pathways implicated in behavioural and cognitive effects of visceral priming. Vagal afferents convey visceral information to the NTS, the major
visceral relay nucleus of the brainstem. The NTS issues a direct noradrenergic projection to forebrain areas such as the amygdala, and via an excitatory input to the
PGi can also activate the ascending noradrenergic system arising in the LC. The LC, in turn, projects to the basal forebrain corticopetal cholinergic system (BF
cholinergic system) as well as to the amygdala and the cortex. There are thus several routes (noradrenergic and cholinergic) by which ascending visceral information
can impact cortical/cognitive processing. Reciprocal interactions between the amygdala and basal forebrain, together with their overlapping targets in the medial
prefrontal cortex, constitute important processing substrates for emotion and cognition.
forebrain cholinergic system and virtually all cortical areas, this
system serves as a unique regulatory modulator of cortical processing
and will be a major focus of the present paper.
The basal forebrain provides the major source of cholinergic input
to the neocortex (Mesulam et al., 1983; Woolf, 1991; Schafer et al.,
1998), exerts a generally excitatory in¯uence on the neocortical mantle
(McCormick & Bal, 1997; Cape et al., 2000; Detari, 2000; Linster &
Hasselmo, 2001; Berntson et al., 2002) and has been shown to promote
cortical plasticity (Metherate & Ashe, 1991; Kilgard et al., 2001;
Miasnikov et al., 2001). Likely related to its activational effects on
cortical processing, the basal forebrain cholinergic system has been
shown to play an important role in attention and cognition (Everitt &
Robbins, 1997; Sarter & Bruno, 1997; Wenk, 1997; Sarter et al.,
2001b; McGaughy et al., 2002), as well as in emotional and motivational processes (Everitt & Robbins, 1997; Berntson et al., 1998).
The NTS/PGi system appears to serve as a central substrate in
integrating descending in¯uences (e.g. from the amygdala and basal
forebrain; Schwaber et al., 1982) with visceral afferent input and
autonomic, particularly sympathetic, out¯ow (Aston-Jones et al.,
1996; Berntson et al., 1998). The PGi provides a major excitatory
input to the LC, which in turn has been linked to behavioural and
emotional activation. The LC has been suggested to represent a general
state-setting mechanism that can facilitate processing of speci®c
stimuli and contexts by more rostral systems (Aston-Jones et al.,
1996). Together, the brainstem circuits of Fig. 1 constitute a salient
route by which the state of sympathetic activity and visceral afferent
input can impact higher neurobehavioural processes.
Visceral afference, rostral systems and
behavioural processes
Visceral afferent activity is known to modulate aspects of behavioural
function. Baroreceptor activity, for example, can inhibit pain transmission through spinal/brainstem circuits and decrease pain perception in
humans (see Dworkin et al., 1994; Edwards et al., 2002). Moreover,
vagal afferent traf®c arising from peripheral immune reactions can
promote central components of the `sickness' response, by triggering
the release of brain interleukin-1 (Goehler et al., 2000; Luheshi et al.,
2000). Visceral afferent traf®c also appears to impact higher level
cognitive and behavioural processes.
Memory and ascending projections to the amygdala
Visceral activation by intraperitoneal administration of epinephrine
has been shown to enhance memory performance in rats (Williams &
McGaugh, 1993; Cahill & McGaugh, 1998; Clayton & Williams,
2000c), and epinephrine infusions in humans have similarly been
ß 2003 Federation of European Neuroscience Societies, European Journal of Neuroscience, 18, 2103±2109
Ascending visceral regulation 2105
reported to enhance memory (Cahill & Alkire, 2003). These and other
®ndings raise the possibility that the memory-potentiating effects of
emotional activation may be attributable in part to endogenous adrenaline and other stress hormones (Cahill & McGaugh, 1998).
The effects of epinephrine on memory appear to re¯ect a peripheral
locus of action, as this macromolecule does not readily cross the
blood±brain barrier (Weil-Malherbe et al., 1959; Hardebo & Owman,
1980; Horinaka et al., 1997), and the effects of intraperitoneal epinephrine on memory are not duplicated by similar or even higher doses
administered directly into the cerebral ventricles (de Almeida et al.,
1983). Rather, systemic epinephrine appears to exert its memorymodulating effects via a peripheral beta-adrenergic activation of
visceral afferents (Introini-Collison et al., 1992), and direct electrical
stimulation of the vagus has also been shown to enhance memory
performance in rats (Clark et al., 1998) and humans (Clark et al.,
1999), even after vagal efferent inactivation (Clark et al., 1998). These
effects are likely attributable to vagal afferent input to the NTS.
Memory enhancement can also be seen after adrenergic activation
of the NTS (Clayton & Williams, 2000a), and the memory-potentiating
effects of systemic epinephrine can be blocked by reversible inactivation (Williams & McGaugh, 1993) or pharmacological blockade of the
NTS (Clayton & Williams, 2000c).
As illustrated in Fig. 1, the rostral ascending pathways from the
NTS underlying memory potentiation include the PGi projection
to the LC (Clayton & Williams, 2000b,d), and noradrenergic projections to the amygdala from the LC and the NTS (Cahill & McGaugh,
1998; Clayton & Williams, 2000a; Power et al., 2002). NTS activation that enhances memory also triggers a local release of norepinephrine in the amygdala (Williams et al., 1998; Clayton & Williams,
2000a). Moreover, direct noradrenergic receptor activation of the
amygdala can enhance memory (Cahill & McGaugh, 1998; Power
et al., 2002), and noradrenergic receptor blockade of this structure
blocks memory potentiation by systemic stress hormones (Cahill &
McGaugh, 1998).
The memory-enhancing effects of noradrenergic stimulation of the
amygdala appear to be mediated in part through projections to the
basal forebrain and the associated activation of ascending corticopetal
cholinergic pathways (McGaugh et al., 2002). The memory-modulating effects of intra-amygdala noradrenergic agonists, for example, are
blocked by selective lesions of the basal forebrain cholinergic system
(Power et al., 2002).
The basal forebrain cholinergic system and cortical processing
In addition to its projection to the amygdala, the LC also issues a major
noradrenergic projection to other telencephalic areas, including an
excitatory projection to basal forebrain cholinergic neurons (Fort et al.,
1995; Zaborszky & Cullinan, 1996; Cape & Jones, 1998). Through this
route, LC inputs from the NTS and the PGi are able to communicate
information related to visceral states and autonomic functions, which
may play an important role in cortical activation and affective reactions
(Aston-Jones et al., 1996; Berntson et al., 1998).
Systemic epinephrine not only enhances memory, but can potentiate
cortical processing of sensory stimuli. As illustrated in Fig. 2, systemic
epinephrine interacts with stimulus intensity, yielding a progressive
enhancement of the cerebral auditory event-related potential (ERP,
Berntson et al., 2003). This effect is dependent on the basal forebrain
corticopetal cholinergic system, as selective lesions (using the immunotoxin 192 IgG saporin) of this cholinergic system attenuate the
evoked response and completely block epinephrine potentiation
(Berntson et al., 2003). Because of the selectivity of the immunotoxin
for basal forebrain cholinergic corticopetal projections (Wiley et al.,
1991; Holley et al., 1994), the effects of the lesions are attributable to
the loss of cholinergic inputs to the cerebral cortex (projections to the
amygdala are spared by the immunotoxin; Heckers et al., 1994). The
response-potentiating effects of epinephrine appear to be mediated by
ascending noradrenergic projections from the LC to the basal forebrain
cholinergic system, as this response potentiation is blocked by local
infusions of an alpha adrenergic antagonist (terazocin) and mimicked
by infusions of an alpha adrenergic agonist (phenylephrine) directly
into the basal forebrain (Knox et al., unpublished observations).
The ®ndings outlined above suggest that the basal forebrain cholinergic system represents a critical nodal point in ascending pathways
carrying information related to autonomic state and visceral afference,
and is capable of priming or biasing the processing of higher cortical
cognitive substrates.
Anxiety, benzodiazepine receptor agents and the basal
forebrain cholinergic system
This ascending corridor and, in particular, the basal forebrain cortical
cholinergic system, has been suggested to play an important role in the
cognitive aspects of anxiety, and appears to serve as an anatomical
substrate for visceral afferent impact on affective information processing (Berntson et al., 1998). One line of evidence supporting this view
comes from the pharmacology of anti-anxiety agents. Benzodiazepine
receptor (BZR) agonists, such as chlordiazepoxide (Librium), diazepam (Valium) and alprazolam (Xanax), in addition to their anti-anxiety
actions, impair cognitive processing. The anxiolytic effects of BZR
agonists are attributable to an enhancement of g-aminobutyric acid
(GABA)-gated chloride ¯ux at the GABA/BZR receptor complex
(Nutt, 1996). In contrast to BZR agonists, BZR inverse agonists
and partial inverse agonists attenuate GABAergic inhibition, and exert
effects that are generally opposite to those of the BZR agonists. These
agents have been reported to have anxiogenic actions in both animals
and humans (for review, see Berntson et al., 1998), and in distinction to
BZR agonists, to enhance certain cognitive processes (Sarter et al.,
1995, 2001a).
Although the central site of action of BZR agents in the bi-directional modulation of anxiety has not been fully clari®ed, the basal
forebrain appears to play a central role (Berntson et al., 1998).
FG7142, a BZR partial inverse agonist and anxiogenic agent, has
been shown to stimulate basal cortical acetylcholine release (Moore
et al., 1995), and to enhance behavioural and autonomic reactions to
anxiety-related stimuli (Berntson et al., 1998). These effects appear to
be causally related, as the anxiogenic actions of this compound are
dependent on the integrity of the basal forebrain cholinergic system,
and are blocked by selective immunotoxic lesions of the basal forebrain cholinergic neurons (Berntson et al., 1996). As illustrated in
Fig. 3, selective lesions of basal forebrain cholinergic neurons also
block the bi-directional modulation of anxiety-related behavioural and
autonomic responses by BZR agonists and inverse agonists in a
conditioned suppression paradigm (Stowell et al., 2000).
A likely basis for the role of the basal forebrain cholinergic system
in anxiety lies in its regulation of cortical/cognitive processing.
Speci®cally, basal forebrain cortical cholinergic activity may foster
the attentional processing of threat-related stimuli and associations,
and thereby contribute to cortical/cognitive aspects of anxiety (Berntson et al., 1998). Cognitive theories of anxiety emphasize attentional
dysfunctions as a major component in the development and persistence
of anxiety disorders. Eysenck (1991), for example, characterizes
anxious individuals as being more likely to attend to threat-related
stimuli and having a more narrowly focused attention. According to
this model, anti-anxiety drugs are hypothesized to produce therapeutic
effects largely via their attention-reducing properties (Berntson et al.,
1998). That is, the association between the anti-anxiety and attentional
ß 2003 Federation of European Neuroscience Societies, European Journal of Neuroscience, 18, 2103±2109
2106 G. G. Berntson et al.
Fig. 2. Epinephrine priming of the cerebral auditory ERP is blocked by lesions of the basal forebrain cortical cholinergic system. Upper left: illustrative examples of
the auditory ERP in control and lesioned animals. Lesions reduce the overall amplitude and increase the peak latency of the ERP. Right: epinephrine interacts with
stimulus intensity to enhance the ERP in control animals. Lesions attenuate overall response amplitude and block epinephrine priming of the auditory ERP. Lower
left: saporin-induced cortical cholinergic deafferentation, indicated by the loss of AChE-positive ®bres in lesioned animals. (A) Low-power and (B) high-power
photomicrographs of a coronal section of frontoparietal cortex in a sham-lesioned rat (200 mm scale in A; 50 mm scale in B). A corresponding section of a lesioned
animal (C and D) shows extensive loss of cholinergic terminals (> 95% loss of AChE-positive axons).
impairing effects of BZR agonists may not be adventitious. Conversely, the anxiogenic effects of BZR inverse agonists may derive from
their activational effects on the basal forebrain cortical cholinergic
system and a resulting attentional focus on, and over-processing of,
threat-related stimuli and contexts (Berntson et al., 1998). The basal
forebrain cholinergic system likely enhances cortical/cognitive processing of a broad range of appetitive as well as aversive stimuli and
associations. It may promote an overall bias toward the processing of
aversive or threat-related cues, however, by amplifying a constitutional
disposition to preferentially attend to and evaluate negative stimuli
(see Cacioppo & Berntson, 1999).
Although the amygdala has been a major focus of interest in the
literature on emotional processes and fear conditioning, it is increasingly apparent that it is only one structure in a network of parallel
circuits involved in emotional processes.
Functional relations among nodal points in
ascending systems
The amygdala and the basal forebrain cholinergic system are reciprocally interconnected, and their functions are closely linked (Alheid,
2003). As illustrated in Fig. 1, both receive ascending inputs from
visceral afferent systems and both project to overlapping ®elds in the
medial prefrontal cortex (which likely has some functional homology
with the cingulate, orbitofrontal and ventromedial prefrontal cortex in
primates; Uylings & van Eden, 1990; Preuss, 1995). Their contributions to affective processes, however, appear to be somewhat distinct.
The amygdala receives information from all sensory modalities (Price,
2003). Through an amygdalo-fugal system (to the hypothalamus and
brainstem), this structure can effect autonomic and neuroendocrine
control, and via an amygdalo-forebrain system (medial prefrontal
cortex, insula and anterior temporal lobe) it may foster affective
information processing and enhance emotional memories (Price,
1999, 2003). Amygdaloid systems have been implicated in the establishment of conditioned fear, in conferring emotional colouring on
stimulus representations, and in regulating behaviour based on reward
and punishments (Cahill & McGaugh, 1998; Lang et al., 2000;
LeDoux, 2000; McGaugh, 2002; Bechara et al., 2003; Damasio,
2003). Although the literature has often focused on the contributions
of the amygdala to fear conditioning, it appears to operate more
generally to augment memory in emotional contexts, whether appetitive or aversive (Cahill & McGaugh, 1998).
ß 2003 Federation of European Neuroscience Societies, European Journal of Neuroscience, 18, 2103±2109
Ascending visceral regulation 2107
Fig. 3. Selective lesions of the basal forebrain cholinergic corticopetal system
reduce anxiety-related behavioural suppression to an aversively conditioned
context, and block the bi-directional modulation anxiety-related effects by BZR
agonists and inverse agonists (Stowell et al., 2000). Bars illustrate the operant
bar-pressing rate (for water reward) after aversive contextual conditioning, in
which non-contingent shocks were presented in the test apparatus. Responding
was reduced, generally, relative to the preconditioning operant level (illustrated
by the horizontal dotted line). The degree of suppression in sham animals was
bi-directionally modulated by BZR agents, being reduced by the BZR agonist
chlordiazepoxide (CDP), and increased by the partial inverse agonist (FG7142).
Basal forebrain lesions have anxiolytic-like actions as they reduced the conditioned suppression under vehicle conditions. In addition, lesions blocked the
bi-directional modulation of suppression by BZR agents.
In contrast to the divergent efferent projections of the amygdala, the
primary output of the basal forebrain cholinergic system is the cerebral
cortex, and its functions more typically manifest in the cognitive/
attentional domain (Everitt & Robbins, 1997; Sarter & Bruno, 1997;
Sarter et al., 2001b). The basal forebrain cholinergic system, by virtue
of its global activational effects on the cortex, appears to enhance or
amplify cortical/cognitive processing. This may include fostering
further evaluative and associative processing of stimuli and contexts
that trigger parallel activation of amygdaloid circuits. The reciprocal
interconnections of the amygdala and the basal forebrain, and the
convergence of their efferents onto medial prefrontal cortex is in
accord with the view that this latter area may be an important
component of processing circuits that regulate autonomic, neuroendocrine and behavioural functions (Bechara et al., 2003; Damasio, 2003).
Although the amygdala may be able to support simple fear conditioning with minimal cortical involvement, the cholinergic enhancement of cortical processing is likely important in more elaborated
evaluative processing, in contextual conditioning and anxiety states
(Berntson et al., 1998; Lang et al., 2000; LeDoux, 2000). This is
consistent with ®nding that lesions of the basal forebrain cholinergic
system, although they do not abolish simple associative conditioning,
block the attentional enhancement of associability when the predictive
relation of a conditioned stimulus is changed (Chiba et al., 1995).
A related question arises as to the functional effects and interactions
among cholinergic and adrenergic pathways at the cortical level. There
are several parallels and interactions among cortical cholinergic and
adrenergic afferents. Acetylcholine has been shown to presynaptically
promote the release of cortical norepinephrine (Wonnacott, 1997).
Moreover, norepinephrine, in addition to enhancing acetylcholine
release by an action at the basal forebrain (see above), may also foster
acetylcholine release by direct or indirect actions at the level of the
cortical cholinergic terminals (Tellez et al., 1999). The effects of
norepinephrine have been reported to show a laminar selectivity within
the cortex, whereby norepinephrine preferentially suppresses intrinsic
compared with sensory afferent inputs, which may serve to enhance
the signal-to-noise ratio for sensory stimuli (Hasselmo et al., 1997).
This is reminiscent of the proposed enhancement of signal-to-noiseratio, as discussed above, by cholinergic inputs to cortical neurons.
Both may synergistically enhance attentional focus on and cortical
processing of salient, adaptively signi®cant environmental stimuli.
Although both acetylcholine and norepinephrine play an important
role in attentional performance, they may in¯uence distinct aspects or
component processes. While the cortical cholinergic input system has
been hypothesized to represent a necessary component of the forebrain
circuitry mediating attentional functions in general, activation of the
ascending noradrenergic systems and noradrenergic modulation of the
basal forebrain corticopetal system appears necessary for the `bottomup' recruitment of attentional processes and capacities in response to
salient, new, stressful or affective stimuli (Robbins et al., 1998; Sarter
et al., 2001b). In most situations demanding attentional capacities,
telencephalic (`top-down') and brainstem (`bottom-up') regulation of
the basal forebrain corticopetal system likely interact to optimize
attentional processing (see also Jodo et al., 1998; Yu & Dayan,
2002). Therefore, in the context of cortical affective information
processing, the corticopetal cholinergic system may be more selectively involved in the cognitive evaluation of affective stimuli and
events (e.g. anxiety, apprehension), whereas the attentional components of lower level affective processes (e.g. simple fear conditioning)
may require activation of the ascending noradrenergic system (see also
Berntson et al., 1998).
Although the present paper has emphasized ascending pathways and
bottom-up in¯uences, it is of note that the amygdala and the medial
prefrontal cortex issue descending projections not only to the hypothalamus and the upper brainstem, but also to autonomic substrates of
the lower brainstem and spinal cord. These include direct projections
to the LC, NTS and autonomic source nuclei in the medulla and
the intermediolateral cell column of the cord (Danielsen et al., 1989;
Neafsey, 1990; Jodo et al., 1998; Chiba et al., 2001). The existence of
such reciprocal ascending and descending circuits could support either
bottom-up- or top-down-driven processing. The ascending limb of
these circuits may serve to bias emotion and cognition, and to guide
behavioural choice (e.g. Bechara et al., 2003), whereas the descending
limb may serve to couple cognitive and emotional states with appropriate somato-visceral support. Such circuits may also support the
`vicious cycle' of reciprocal ascending/descending activity that underlies conditions such as panic disorder (Goetz et al., 1993; Joiner et al.,
1999).
Overview
The neurobehavioural literature has often focused on higher neuraxial
levels and top-down in¯uences, but comprehensive understanding of
neurobehavioural systems will require attention also to important
bottom-up in¯uences that serve to bias or set the tone of higher level
substrates. William James asserted that `. . . the emotional brainprocesses not only resemble the ordinary sensorial brain-processes,
but in very truth are nothing but such processes variously combined.'
(James, 1884, p. 188). There is no doubt that visceral afference can
impact cognition and emotion, but not in the sense of an identity
between the visceral perception and the emotion, which was a central
aspect of the James view. Rather, the in¯uence of ascending visceral
feedback is more subtle and diverse (Cacioppo et al., 1992). Nodal
points within these ascending networks include the NTS, the PGi and
the LC, which are highly sensitive to autonomic and visceral states,
and issue rostral (e.g. noradrenergic) projections to higher neuraxial
levels. Also important in this model of neurobehavioural organization
are those structures and systems that translate these ascending
ß 2003 Federation of European Neuroscience Societies, European Journal of Neuroscience, 18, 2103±2109
2108 G. G. Berntson et al.
in¯uences into effects on behaviour and cognition. These include the
amygdala, which appears to confer affective colouring on stimuli and
contexts, and the basal forebrain cortical cholinergic system, which
may promote attentional and cognitive processing of these stimuli and
contexts. It is the broader conceptualization of the multiple levels of
neuraxial processing and the reciprocally interacting top-down and
bottom-up processes that will likely yield the most fruitful advances in
our basic understanding of neurobehavioural systems (Mesulam, 1998;
Cacioppo et al., 2000), as well as in clinical applications derived from
this understanding. Consequently, an important direction for future
research is the elucidation of the multiple levels of organization in
affective systems, and the reciprocal interactions among these levels of
function.
Acknowledgements
Preparation of this paper was supported in part by grants from the NHLBI
(HL54428), NINDS (NS37016) and NIMH (MH63114).
Abbreviations
BZR, benzodiazepine receptor; ERP, event-related potential; GABA, g-aminobutyric acid; LC, locus coeruleus; NTS, nucleus tractus solitarius; PGi,
nucleus paragigantocellularis.
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