Enhanced Excitability of the Human Visual
Cortex Induced by Short-term Light
Deprivation
Babak Boroojerdi, Khalaf O. Bushara1, Brian Corwell,
Ilka Immisch1, Fortunato Battaglia, Wolf Muellbacher1 and
Leonardo G. Cohen
Long-term deprivation of visual input for several days or weeks leads
to marked changes in the excitability and function of the occipital
cortex. The time course of these changes is poorly understood. In
this study, we addressed the question whether a short period of light
deprivation (minutes to a few hours) can elicit such changes in
humans. Noninvasive transcranial magnetic stimulation (TMS) of the
human occipital cortex can evoke the perception of flashes or spots
of light (phosphenes). To assess changes in visual cortex excitability
following light deprivation, we measured the minimum intensity of
stimulation required to elicit phosphenes (phosphene threshold) and
the number of phosphenes elicited by different TMS stimulus
intensities (stimulus–response curves). A reduced phosphene
threshold was detected 45 min after the onset of light deprivation
and persisted for the entire deprivation period (180 min). Following
re-exposure to light, phosphene thresholds returned to predeprivation values over 120 min. Stimulus–response curves were
significantly enhanced in association with this intervention. In a
second experiment, we studied the effects of light deprivation on
functional magnetic resonance imaging (fMRI) signals elicited by
photic stimulation. fMRI results showed increased visual cortex
activation after 60 min of light deprivation that persisted following 30 min of re-exposure to light. Our results demonstrated a
substantial increase in visual cortex excitability. These changes may
underlie behavioral gains reported in humans and animals associated
with light deprivation.
human occipital cortex using transcranial magnetic stimulation
(TMS). When applied to the occipital cortex, TMS can elicit the
perception of ‘phosphenes’, f lashes/spots of light in the absence
of visual stimuli (Marg and Rudiak, 1994). The minimum TMS
intensity that evokes phosphenes (phosphene threshold, PT) and
the stimulus–response curves for the phosphene elicitation
(average number or intensity of reported phosphenes at different stimulation intensities) convey information on visual cortex
excitability (Afra et al., 1998; Aurora et al., 1998). The second
hypothesis was tested using blood oxygenation level dependent
(BOLD) functional magnetic imaging resonance (fMRI) as an
indirect measure of visual cortex neural activity during photic
stimulation (Ogawa et al., 1990). PTs, stimulus–response cur ves
and occipital activation in fMRI were determined in our study as
a function of time following light deprivation (180 min in TMS
studies and 60 min in fMRI experiments).
Introduction
Deafferentation results in cortical reorganization in motor
(Kujala et al., 1995) and sensory (Wall et al., 1986; Allard et al.,
1991; Merzenich and Jenkins, 1993) systems. In the visual
system, retinal lesions lead to rapid increases in the receptive
fields of cortical cells near the edge of the deprived occipital
cortex (Gilbert and Wiesel, 1992; Pettet and Gilbert, 1992).
Behaviorally, visual deprivation leads to better consolidation of
spatial memory in animals (Worsham and D’A mato, 1973;
Grimm and Samuel, 1976) and results in lower visual recognition
thresholds in normal humans (Suedfeld, 1975). In the absence of
vision, blind individuals may experience visual hallucinations
(Charles–Bonnet syndrome), interpreted as a release of cortical
circuits that follows deprivation of sensory input (Cogan, 1973;
Rosenbaum et al., 1987; Fernandez et al., 1997). Moreover,
visual deprivation may induce substantial changes in information
processing in other modalities. For example, the deprived visual
cortex appears to be significantly involved in tactile (Cohen et
al., 1997) and auditory (Kujala et al., 1995) discrimination tasks
in blind individuals. Therefore, chronic visual deprivation leads
to marked changes in excitability and function of the occipital
cortex. The time course of these changes is poorly understood.
Here, we hypothesized that light deprivation would result
in (i) enhanced excitability of the occipital cortex, and (ii)
increased activation of the occipital cortex to incoming visual
input. The first hypothesis was evaluated by directly stimulating
Human Cortical Physiology Section, and 1Human Motor
Control Section, National Institute of Neurological Disorders
and Stroke, National Institutes of Health, Bethesda, MD, USA
Design and Methods
Subjects
Sixteen healthy normal volunteers with no history of migraine, visual
deficits or neurological abnormalities were investigated (11 men, 5
women, age 26.8 ± 5.4 years) in TMS experiments. Five different normal
volunteers (2 men, 3 women, mean age 32 ± 2.6 years) were studied using
fMRI. All subjects gave their written informed consent, and the protocol
was approved by the Institutional Review Board. Subjects were naive to
the experimental purposes.
Transcranial Magnetic Stimulation
All experiments were conducted in a dark room with just enough light for
the investigator to perform the study (residual luminance in the room was
near zero). Additionally, completely non-transparent goggles were placed
to accomplish total darkness. Subjects wore a cotton swimmer’s cap. A
grid of 3 × 3 points, with each point 2 cm apart, was drawn on the cap
with the center of the grid overlying Oz (International 10/20 system). In
addition to these occipital positions, TMS was delivered to parietal
locations P3 and P4 and to the air (near the ear). Additionally, sham
stimulation was delivered to occipital positions (involving tilted
placement of the coil so that the sound, sensation and muscle twitch
elicited by the coil at the back of the head was similar to occipital
stimulation). The different positions and air were randomly stimulated.
Subjects were instructed to report any potential subjective sensations
(visual, tactile or/and auditory) evoked by TMS. A Cadwell high-speed
magnetic stimulator (Cadwell Laboratories Inc., Kennewick, WA),
equipped with a 7.5 cm figure-of-eight shaped coil (coil orientation
parallel to the midline and current f lowing in the cranio-caudal direction)
was used to deliver magnetic stimuli.
If a phosphene was reported, subjects were asked to describe its
shape, color, brightness (on an arbitrary scale of 1–5, 5 the brightest
phosphene) and location in the visual field as being displayed on the face
of an imaginary clock in front of them.
The entire course of the study consisted of four main sessions and three
control experiments.
Cerebral Cortex May 2000;10:529–534; 1047–3211/00/$4.00
Session 1
This had an exploratory purpose to identify subjects with reproducible
TMS-induced phosphenes. Subjects were initially blindfolded in a dark
room. Approximately 45 min following the onset of light deprivation,
TMS was delivered to all grid points (five stimulations for each condition),
starting at 40% maximum stimulator output and increasing in 10% steps
until phosphenes were reported or maximum stimulator output was
reached. If single-pulse TMS failed to elicit phosphenes (in 11/16
subjects), the same procedure was repeated using pairs of TMS stimuli of
equal stimulus intensity separated by a 50 ms interstimulus interval
(Ray et al., 1998). Stimuli (single or pairs) were given every 10 s. Only
phosphenes reported in the visual field contralateral to the site of the
stimulation were considered accurate. Additionally, consistency in
the report of phosphene characteristics upon stimulation of the same
position was evaluated. A ll subjects who reported accurate and
consistent phosphenes in session 1 participated in session 2. Pairs of TMS
stimuli were used in the following sessions.
Session 2
This session was designed to test the reliability and intersession
reproducibility of the reported phosphenes. Stimulation parameters and
sites were the same as those used successfully in session 1. Subjects could
continue with the study only if their accuracy level was >80%, and if
control and sham stimulations failed to produce phosphenes. Subjects
meeting these criteria participated in sessions 3 and 4.
Session 3
Five subjects met these criteria and participated in this session. PT was
defined as the minimum intensity of stimulation able to elicit phosphenes
in three out of five trials at any given scalp location. Stimulation intensities
started at 30% maximum stimulator output and were increased in 2%
steps. Stimulus–response curves were also obtained to determine the
number and intensity of the reported phosphenes. PTs were determined
at the onset of the light deprivation period and 45, 90, 135 and 180 min
later. Stimulus–response curves were determined at the onset of the
experiment and after 180 min of light deprivation.
Extraocular muscle EMG activity and eye movements were monitored
using a Counterpoint electromyograph (Dantec Medical, Skovlunde,
Denmark) and Ag/AgCl electrodes attached to the right orbicularis oculi
muscle and to the lower lid. At the end of each session, subjects were
asked to report sensations elicited by voluntary blinking.
Session 4
In this session, subjects underwent 90 min of light deprivation. Following
this time period, they were re-exposed to room light (390 lux) and PTs
were tested repetitively for at least 120 min.
Control Experiments (Sessions 5, 6 and 7)
These experiments were performed with subjects who had participated
in sessions 3 and 4. In session 5, reproducibility of the deprivationinduced changes in PT was investigated in three subjects. PT was
determined at 45 min intervals during 135 min of light deprivation.
Session 6 was designed to assess the effects of repetitively testing PTs
without light deprivation. PTs were measured twice within 45 min
without light deprivation (n = 5). In session 7, subjects (n = 5) underwent
repetitive determination of PTs (also in the absence of light deprivation)
after one night of sleep deprivation to mimic the mild drowsiness
reported in the light deprivation experiments.
Functional Magnetic Resonance Imaging
fMRI was performed on a 1.5 T GE Signa scanner equipped with whole
body echo-planar gradients and a standard birdcage head coil. Using
gradient-echo echo-planar imaging (EPI), two sets of 160 functional
images were acquired in each subject before light deprivation, after 60
min of light deprivation, and after 30 min of re-exposure to room light
(390 lux). Visual stimuli were presented binocularly via well-fitted
lightproof goggles by f lashing a matrix of 5 × 6 red LED (arranged in
rectangular shape 1.2 × 1.5 cm) at 2 Hz. Head movement was minimized
using an adjustable headband and cushions. Functional images consisted
530 Enhanced Visual Cortex Excitability Following Light Deprivation • Boroojerdi et al.
of T2*-weighted images (64 × 64 matrix, 24 × 24 cm FOV, ±62.5 kHz
bandwidth, TR/TE = 2500/50 ms) at each of 17 slice locations (5 mm apart,
no gap) covering the occipital lobes. The total scanning time for each set
was 6 min and 40 s consisting of 30 s epochs of rest in between photic
stimulation. Anatomical scans consisted of multiple high-resolution,
T1-weighted whole-brain axial three-dimensional spoiled grass (3D SPGR)
data set (256 × 256 × 124, 24 cm in-plane FOV, 1.0–1.2 mm slice
thickness, f lip angle of 30°, TR/TE = 35/ 8 ms, 1 NEX).
Imaging time series were realigned, normalized to standard Talairach
stereotaxic space and smoothed with a Gaussian kernel of 5 mm
full-width half-maximum using Statistical Parametric Mapping software
(SPM96, http://w w w.fil.ion.ucl.ac.uk/spm). After removing global
changes in activity using proportional scaling, statistical parametric maps
(SPMs) of voxels with significant MR signal increase during visual
stimulation compared to rest (z score > 3.09, P < 0.05 corrected for
multiple comparisons) were constructed.
Statistical Analysis
PTs and stimulus–response curves were compared at different time
intervals following the onset of deafferentation using a repeated-measures
ANOVA model. Individual intervals were compared using a two-tailed,
paired t-test. The number of significantly activated voxels in the fMRI
experiments and the mean percentage change in signal intensity before
and after light deprivation and after re-exposure to light were compared
using paired Wilcoxon signed-rank tests. The significance level was set to
P < 0.05.
Results
Perceptions Elicited by Transcranial Magnetic
Stimulation
Of the 16 participants in the study, nine (56%) reported visual
sensations induced by TMS, similar to the findings of other
investigators (Meyer et al., 1991). Of these nine subjects, five
reported accurate and consistent phosphenes (see Design and
Methods). Colored phosphenes were reported by three subjects
at high stimulation intensities (70% stimulator output and
above). Examples of these reports included: ‘a bright red f lash at
9 o’clock’, ‘ a yellow star at 1 o’clock’ and ‘a greenish sphere at 5
o’clock’. None of the subjects reported phosphenes following
control or sham stimulations. No moving (kinetic) phosphenes
were reported. Optimal grid points for elicitation of phosphenes
were always located in the upper third of the grid.
Phosphene Thresholds
All subjects showed a decreased PT over the course of the 3 h
period of light deprivation. During this time period, mean PT
dropped from 63.0 ± 8.3 to 48.0 ± 7.6% (P = 0.0001) (Fig. 1A,B).
Although a large reduction in the PT occurred during the first 45
min, a significant decrease of PT could still be detected between
45 and 90 min after onset of the deprivation (from 54.0 ± 5.5 to
51.0 ± 8.2%, P = 0.02). This decrease in the PT was reproduced
in control session 5 (decrease of PT from 70.0 ± 10.0 to 50.0 ±
8.7% after 135 min; P = 0.02).
PTs returned to normal values ∼120 min following reexposure
to light (session 4) (Fig. 2). In the absence of light deprivation,
PTs tested 45 min apart showed no significant changes (control
session 6; PT 53.0 ± 9.7 and 52.0 ± 8.4, P = 0.37). Similarly,
testing during sleep deprivation-induced drowsiness did not
result in PT changes in the absence of light deprivation (control
session 7; PT 53.0 ± 9.7 and 54.0 ± 12.0, P = 0.91).
In three subjects, phosphenes could be elicited below the TMS
intensity, which led to blink responses or eye movements.
Voluntary blinking did not produce phosphenes in any subject.
Figure 2. Time course of the phosphene thresholds (PTs) following 90 min of visual
deprivation and re-exposure to room light (session 4). PTs returned to predeprivation
values within ∼120 min.
Figure 1. Phosphene thresholds (PTs) over the time course of 180 min after the onset
of visual deprivation. (a) Mean PT had a significant decrease after 45 and 90 min. Error
bars indicate standard errors. (b) Individual PTs showed a decrease over the time course
of the study in all subjects.
Figure 3. Average number of the elicited phosphenes as a function of stimulation
intensity at the onset and after 180 min of light deprivation. A significantly higher
number of phosphenes could be elicited at 50 and 60% stimulation intensity after 180
min. Similar plateau levels were reached with higher stimulation intensities.
Phosphene Stimulus–Response Curves
Stimulus–response curves for the number of elicited phosphenes
180 min after light deprivation onset was steeper than that
obtained before light deprivation. These differences became
significant at 50 and 60% maximum stimulator output (P = 0.02).
At higher stimulus intensities, a plateau level was reached
(Fig. 3). Although the average reported intensity of phosphenes
had a higher value after 180 min compared to the onset of
the experiment at intensities <70%, this difference was not
significant (Fig. 4).
fMRI
Before light deprivation, the visual cortex was significantly
activated in response to photic stimulation in all subjects. The
Tailarach coordinates of peak activity were (x, y, z ± SD) –1 ±
–7.0, –82.6 ± –16.4, 12.8 ± 14.0 corresponding to Brodmann’s
areas 17, 18 and 19. In all subjects, the number of activated
voxels and mean change in MR intensity increased significantly
following 60 min of light deprivation (P = 0.043 for both
parameters). This increase was maintained in all subjects 30 min
after reexposure to light (Fig. 5A,B). There was no significant
activation in the lateral geniculate bodies.
Discussion
Our results demonstrated that the excitability of the visual cortex
to TMS and its hemodynamic responses to incoming visual input
are increased following light deprivation.
Figure 4. Average intensity of the reported phosphenes at different stimulation
intensities at the onset and after 180 min of visual deprivation. Although the reported
intensity after 180 min of visual deprivation was higher, this difference was not
statistically significant.
Brain Regions Responsible for TMS-induced Phosphenes
Phosphenes can be elicited by direct occipital electrical
stimulation (Bak et al., 1990) and also by TMS delivered to
occipital sites (Meyer et al., 1991). A similar occipital site at a
depth of 1.5–2 cm from the scalp surface has been identified
as that mediating the phenomenon of TMS-induced visual
suppression (Epstein et al., 1996), possibly in medially located
bends in geniculo-calcarine or corticofugal fibers (Amassian et
al., 1994). Given the relatively low TMS stimulus intensities used
in our study and the use of a focal coil, a superficial stimulation
Cerebral Cortex May 2000, V 10 N 5 531
Figure 5. (a) Number of activated voxels (log) and (b) mean MR signal intensity change of activated voxels in the occipital cortex to photic stimulation before, 60 min after the onset
of visual deprivation and 30 min following re-exposure to light. A significant increase after 60 min of light deprivation could be seen in both parameters, which was maintained following
30 min of re-exposure to light. (c) An example of visual cortex activation in one subject at three different levels. Error bars indicate standard errors.
site (which could include the visual cortex and adjacent
subcortical fibers) seems to be the most probable site of
phosphene induction.
For different reasons, it is unlikely that TMS directly
stimulated the retina under our experimental conditions. First,
optimal scalp positions for eliciting phosphenes were occipital
(>8 cm away from the retina) and the magnitude of the electric
field induced by TMS drops rapidly as a function of the distance
between the coil and target neural structures (Maccabee et al.,
1991a,b; Roth et al., 1991). Second, more anterior stimulating
positions closer to the retina failed to elicit phosphenes. Third,
there is a clear topographic specificity of phosphenes elicited by
TMS (contralateral to the stimulated position). Fourth, while
light deprivation can increase retinal excitability during a period
of adaptation of ∼30–40 min (Peachey et al., 1992a,b), PTs in our
study continued to decline beyond this time period. Therefore,
the decreased threshold of TMS-induced phosphenes identified
after light deprivation is likely to ref lect genuine changes in
occipital cortex excitability.
532 Enhanced Visual Cortex Excitability Following Light Deprivation • Boroojerdi et al.
In additional control experiments, we found that phosphenes
usually occurred independently of eye movements or blinking.
Similarly, TMS intensities required to elicit phosphenes were
below those needed to induce eye movements or blinking.
Furthermore, voluntary blinking failed to elicit phosphenes. For
these reasons, we conclude that TMS-induced phosphenes as
studied here do not represent perceptual correlates of intra- or
extraocular movements. Another control experiment was
designed to test the effects of drowsiness (experienced by most
subjects during the light deprivation period) on cortical
excitability. We found that drowsiness induced by sleep deprivation failed to elicit changes in PT and therefore cannot explain
the excitability changes associated with light deprivation.
Another control experiment tested the effects of repetitively
stimulating the occipital cortex with TMS on PTs. Repetitive
determination of PTs in the absence of light deprivation also
failed to induce excitability changes in the occipital cortex,
demonstrating that application of TMS alone cannot elicit the
excitability changes described.
Changes in occipital cortex responses to visual stimuli
following light deprivation
fMRI provides an objective measure of cortical activity that,
unlike TMS-evoked phosphenes, did not rely on the subjects’
perceptions. The results from this fMRI study showed increased
neural activity in the occipital cortex to incoming visual inputs
following light deprivation that persisted for at least 30 min after
reexposure to light. This result could be explained if the
excitability of the visual cortex increased following light deprivation. Indeed, increased fMRI signal is detected in situations
with increased cortical excitability such as in the Charles–
Bonnet syndrome or in patients with unilateral occipital lobe
epilepsy (Jueptner and Weiller, 1995; Ff ytche et al., 1998,
Masuoka et al., 1999). While it is conceivable that changes in
excitability in the occipital cortex result in enhanced activation
to incoming visual input, a cause–effect relationship between
both cannot be assessed in this experimental design. An
alternative explanation is that the increased visual cortex activity
is secondary to light deprivation-induced changes in the visual
pathway distal to the visual cortex (most likely the retina). Such
a change would result in a net increase in the input reaching the
cortex. Against this interpretation is the stability of changes in
visual cortex activity beyond 30 min (in which retinal adaptation
is completed) after re-exposure to light (Fig. 5A) (Marmor, 1989;
Peachey et al., 1992b). If the enhancement in occipital signal
was secondar y to retinal excitability changes, it should have
substantially decreased within 30 min.
Possible Mechanisms of the Short-term Increase in
Visual Cortex Excitability
The fast development of the changes in the PT is compatible with
‘unmasking’ of previously existing connections at a cortical level.
Several mechanisms could mediate this effect. A decrease in
GABA receptors and the GABA-synthesizing enzyme (glutamic
acid decarboxylase, GAD) has been found in different animal
models of deafferentation in the visual cortex (Hendry et al.,
1990; Jones, 1993; Rosier et al., 1995). GABA levels are known
to change in humans within minutes of deafferentation (Levy et
al., 1999) or after administration of a single oral dose of the
antiepileptic vigabatrin (Petroff and Rothman, 1998). Therefore,
changes in GABA levels could be operational in this setting. In
addition to GABA, regulation of activity of muscarinic acetylcholine receptors may play an important role in visual cortex
plasticity. For example, intracortical infusion of anticholinergic
drugs inhibits plasticity in kitten visual cortex (Gu and Singer,
1993). N-Methyl-D-aspartate (NMDA) receptors may play a
potential role in this phenomenon too. Blockade of NMDA
receptors reduces ocular dominance plasticity in animals (Bear
et al., 1990; Rauschecker et al., 1990; Daw, 1994). The relative
contribution of these mechanisms to our results is presently
under investigation.
In conclusion, our results demonstrated an enhanced excitability of the visual cortex associated with short-term visual
deprivation. This phenomenon may underlie behavioral gains
reported following light deprivation in humans and in animals.
Notes
This work was partially supported by Grant Bo 1576/1–1 to B.B. from the
Deutsche Forschungsgemeinschaft and by a grant from OSM-NIH. The
authors are grateful to Dr M. Hallett for his comments on the manuscript,
to Dr T. Mima (NINDS, Bethesda) for his technical help in some of the
experiments, and to D. Schoenberg, MS, for skilful editing.
Address correspondence to Dr Leonardo G. Cohen, Building 10, Room
5N 234, National Institutes of Health, 10 Center Drive, MSC 1428,
Bethesda, MD 20892-1428, USA. Email: [email protected].
References
Afra J, Mascia A, Gerard P, Maertens de Noordhout A, Schoenen J (1998)
Interictal cortical excitability in migraine: a study using transcranial
magnetic stimulation of motor and visual cortices. Ann Neurol
44:209–215.
Allard T, Clark SA, Jenkins WM, Merzenich MM (1991) Reorganization of
somatosensory area 3b representations in adult owl monkeys after
digital syndactyly. J Neurophysiol 66:1048–1058.
Amassian VE, Maccabee PJ, Cracco RQ, Cracco JB, Somasundaram M,
Rothwell JC, et al. (1994) The polarity of the induced electric field
inf luences magnetic coil inhibition of human visual cortex: implications for the site of excitation. Electroenceph Clin Neurophysiol
93:21–26.
Aurora SK, Ahmad BK, Welch KM, Bhardhwaj P, Ramadan NM (1998)
Transcranial magnetic stimulation confirms hyperexcitability of
occipital cortex in migraine. Neurology 50:1111–1114.
Bak M, Girvin JP, Hambrecht FT, Kufta CV, Loeb GE, Schmidt EM (1990)
Visual sensations produced by intracortical microstimulation of the
human occipital cortex. Med Biol Engng Comput 28:257–259.
Bear MF, Kleinschmidt A, Gu QA, Singer W (1990) Disruption of
experience-dependent synaptic modifications in striate cortex by
infusion of an NMDA receptor antagonist. J Neurosci 10:909–925.
Cogan DG (1973) Visual hallucinations as release phenomena. Albrecht
Von Graefe’s Arch Klin Exp Ophthalmol 188:139–50.
Cohen LG, Celnik P, Pascual-Leone A, Corwell B, Falz L, Dambrosia J, et
al. (1997) Functional relevance of cross-modal plasticity in blind
humans. Nature 389:180–183.
Daw N W (1994) Mechanisms of plasticity in the visual cortex. The
Friedenwald Lecture. Invest Ophthalmol Vis Sci 35:4168–4179.
Epstein CM, Verson R, Zangaladze A (1996) Magnetic coil suppression of
visual perception at an extracalcarine site. J Clin Neurophysiol
13:247–252.
Fernandez A, Lichtshein G, Vieweg W V (1997) The Charles–Bonnet
syndrome: a review. J Nerv Ment Dis 185:195–200.
Ffytche DH, Howard RJ, Brammer MJ, David A, Woodruff P, Williams S
(1998) The anatomy of conscious vision: a fMRI study of visual
hallucinations. Nature Neurosci 1:738–742.
Fishman GA, Pulluru P, Alexander KR, Derlacki DJ, Gilbert LD (1994)
Prolonged rod dark adaptation in patients with cone–rod dystrophy.
Am J Ophthalmol 118:362–367.
Gilbert CD, Wiesel TN (1992) Receptive field dynamics in adult primary
visual cortex. Nature 356:150–152.
Grimm VE, Samuel D (1976) The effects of dark isolation on the performance of a white–black discrimination task in the rat. Int J Neurosci
7:1–7.
Gu Q, Singer W (1993) Effects of intracortical infusion of anticholinergic
drugs on neuronal plasticity in kitten striate cortex. Eur J Neurosci
5:475–485.
Hendry SH, Fuchs J, deBlas AL, Jones EG (1990) Distribution and
plasticity of immunocytochemically localized GA BA A receptors in
adult monkey visual cortex. J Neurosci 10:2438–2450.
Jones EG (1993) GABAergic neurons and their role in cortical plasticity in
primates. Cereb Cortex 3:361–372.
Jueptner M, Weiller C (1995) Review: does measurement of regional
cerebral blood f low ref lect synaptic activity? Implications for PET and
fMRI. Neuroimage 2:148–156.
Kujala T, Huotilainen M, Sinkkonen J, Ahonen AI, Alho K, Hamalainen
MS, et al. (1995) Visual cortex activation in blind humans during
sound discrimination. Neurosci Lett 183:143–146.
Levy LM, Ziemann U, Chen R, Cohen LG (1999) Rapid modulation of
GABA in human cortical plasticity demonstrated by magnetic resonance spectroscopy. Neurology 52:A88.
Maccabee PJ, Amassian VE, Cracco RQ, Cracco JB, Eberle L, Rudell A
(1991a) Stimulation of the human nervous system using the magnetic
coil. J Clin Neurophysiol 8:38–55.
Maccabee PJ, Amassian VE, Eberle LP, Rudell AP, Cracco RQ, Lai KS, et
al. (1991b) Measurement of the electric field induced into
inhomogeneous volume conductors by magnetic coils: application to
human spinal neurogeometry. Electroenceph Clin Neurophysiol 81:
224–237.
Marg E (1991) Magnetostimulation of vision: direct noninvasive stimulation of the retina and the visual brain. Optom Vis Sci 68:427–440.
Marg E, Rudiak D (1994) Phosphenes induced by magnetic stimulation
Cerebral Cortex May 2000, V 10 N 5 533
over the occipital brain: description and probable site of stimulation.
Optom Vis Sci 71:301–311.
Marmor MF (1989) An international standard for electroretinography.
Doc Ophthalmol 73:299–302.
Masuoka LK, Anderson AW, Gore JC, McCarthy G, Spencer DD, Novotny
EJ (1999) Functional magnetic resonance imaging identifies abnormal
visual cortical function in patients with occipital lobe epilepsy.
Epilepsia 40:1248–1253.
Merzenich MM, Jenkins WM (1993) Reorganization of cortical
representations of the hand following alterations of skin inputs
induced by nerve injury, skin island transfers, and experience. J Hand
Ther 6:89–104.
Meyer BU, Diehl R, Steinmetz H, Britton TC, Benecke R (1991) Magnetic
stimuli applied over motor and visual cortex: inf luence of coil
position and field polarity on motor responses, phosphenes, and eye
movements. Electroenceph Clin Neurophysiol Suppl 43:121–134.
Ogawa S, Lee TM, Kay AR, Tank DW (1990) Brain magnetic resonance
imaging with contrast dependent on blood oxygenation. Proc Natl
Acad Sci USA 87:9868–9872.
Peachey NS, Alexander KR, Derlacki DJ, Fishman GA (1992a) Light
adaptation, rods, and the human cone f licker ERG. Vis Neurosci
8:145–150.
Peachey NS, Arakawa K, Alexander KR, Marchese AL (1992b) Rapid and
slow changes in the human cone electroretinogram during light and
dark adaptation. Vis Res 32:2049–2053.
Petroff OA, Rothman DL (1998) Measuring human brain GABA in vivo:
effects of GA BA-transaminase inhibition with vigabatrin. Mol
Neurobiol 16:97–121.
534 Enhanced Visual Cortex Excitability Following Light Deprivation • Boroojerdi et al.
Pettet MW, Gilbert CD (1992) Dynamic changes in receptive-field size in
cat primary visual cortex. Proc Natl Acad Sci USA 89:8366–8370.
Rauschecker JP, Egert U, Kossel A (1990) Effects of NMDA antagonists on
developmental plasticity in kitten visual cortex. Int J Dev Neurosci
8:425–435.
Ray PG, Meador KJ, Epstein CM, Loring DW, Day LJ (1998) Magnetic
stimulation of visual cortex: factors inf luencing the perception of
phosphenes. J Clin Neurophysiol 15:351–357.
Rosenbaum F, Harati Y, Rolak L, Freedman M (1987) Visual hallucinations
in sane people: Charles–Bonnet syndrome. J Am Geriatr Soc 35:
66–68.
Rosier AM, Arckens L, Demeulemeester H, Orban GA, Eysel UT, Wu YJ, et
al. (1995) Effect of sensory deafferentation on immunoreactivity of
GABAergic cells and on GABA receptors in the adult cat visual cortex.
J Comp Neurol 359:476–489.
Roth BJ, Saypol JM, Hallett M, Cohen LG (1991) A theoretical calculation
of the electric field induced in the cortex during magnetic
stimulation. Electroenceph Clin Neurophysiol 81:47–56.
Suedfeld P (1975) The benefits of boredom: sensory deprivation
reconsidered. Am Scient 63:60–69 [review].
Wall JT, Kaas JH, Sur M, Nelson RJ, Felleman DJ, Merzenich MM (1986)
Functional reorganization in somatosensory cortical areas 3b and 1 of
adult monkeys after median nerve repair: possible relationships to
sensory recovery in humans. J Neurosci 6:218–2133.
Worsham RW, D’A mato MR (1973) A mbient light, white noise, and
monkey vocalization as sources of interference in visual short-term
memory of monkeys. J Exp Psychol 99:99–105.