Enhanced excitability of the human visual cortex induced by short-term light deprivation

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.     

The kinetic occipital region in human visual cortex

In the present study we showed that the kinetic occipital (KO) region, located laterally in occipital cortex approximately 20 mm behind human MT/V5, can be strongly and bilaterally activated under passive viewing conditions. We used continuous, randomly changing visual stimulation to compare kinetic gratings to uniform motion and kinetic gratings to luminance defined gratings. The KO activations under these passive conditions are stronger than those observed when the two types of gratings are compared under active conditions, i.e. while subjects perform a task (counting gratings of a given orientation). Region KO was shown to process both shape and motion information, the conjunction of which is typically present in kinetic contours. Area MT/V5 also processes these two aspects of visual stimulation but favors motion signals. Clear segregation of shape and motion processing was observed only in occipitotemporal and parietal regions respectively. Although neurons with properties similar to those derived from the conditions activating the KO region have been documented in the macaque monkey, their location seems inappropriate for them to correspond to the KO activation observed in humans.      

Vestibular inputs to human motion-sensitive visual cortex

Two crucial sources of information available to an organism when moving through an environment are visual and vestibular stimuli. Macaque cortical area MSTd processes visual motion, including cues to self-motion arising from optic flow and also receives information about self-motion from the vestibular system. In humans, whether human MST (hMST) receives vestibular afferents is unknown. We have combined 2 techniques, galvanic vestibular stimulation and functional MRI (fMRI), to show that hMST is strongly activated by vestibular stimulation in darkness, whereas adjacent area MT is unaffected. The activity cannot be explained in terms of somatosensory stimulation at the electrode site. Vestibular input appears to be confined to the anterior portion of hMST, suggesting that hMST as conventionally defined may contain 2 subregions. Vestibular activity was also seen in another area previously implicated in processing visual cues to self-motion, namely the cingulate sulcus visual area (CSv), but not in visual area V6. The results suggest that cross-modal convergence of cues to self-motion occurs in both hMST and CSv.     

High-frequency activity in human visual cortex is modulated by visual motion strength

A central goal in systems neuroscience is to understand how the brain encodes the intensity of sensory features. We used whole-head magnetoencephalography to investigate whether frequency-specific neuronal activity in the human visual cortex is systematically modulated by the intensity of an elementary sensory feature such as visual motion. Visual stimulation induced a tonic increase of neuronal activity at frequencies above 50 Hz. In order to define a functional frequency band of neuronal activity, we parametrically investigated which frequency band displays the strongest monotonic increase of responses with strength of visual motion. Consistently in all investigated subjects, this analysis resulted in a functional frequency band in the high gamma range from about 60 to 100 Hz in which activity reliably increased with visual motion strength. Using distributed source reconstruction, we found that this increase of high-frequency neuronal activity originates from several extrastriate cortical regions specialized in motion processing. We conclude that high-frequency activity in the human visual motion pathway may be relevant for encoding the intensity of visual motion signals.     

Structure--function spatial covariance in the human visual cortex.

The value of sulcal landmarks for predicting functional areas was quantitatively examined. Medial occipital sulci were identified using anatomical magnetic resonance images to create individual cortical-surface models. Functional visual areas were identified using retinotopically organized visual stimuli, and positron emission tomography subtraction imaging with intra-subject averaging. Functional areas were assigned labels by placement along the cortical surface from V1. Structure-function spatial covariances between sulci and functional areas, and spatial covariances among functional areas, were determined by projecting sulcal landmarks and functional areas into a standardized stereotaxic space and computing the 'r' statistics. A functional area was considered to spatially covary with a sulcus or another functional area if their geometric centers correlated significantly (P < 0.05) in two or more axes. Statistically significant spatial covariances were found for some, but not all comparisons. The finding of significant spatial covariances within a standardized stereotaxic space indicates that nine-parameter spatial normalization does not account for all the predictive value of structural or functional locations, and may be improved upon by using selected sulcal and functional landmarks. The present findings quantify for the first time the strength of structure--function spatial covariance and comment directly on developmental theories addressing the etiology of structure--function correspondence.     

Experience-dependent regulation of the zincergic innervation of visual cortex in adult monkeys

Zinc is packaged in, and released from, a subset of glutamatergic synapses in the mammalian telencephalon where it has been shown to act as a potent neuromodulator. In order to establish the functional role for zincergic neurons in visual cortical function and plasticity we have compared the topographic distribution of zincergic terminals in the primary visual cortex (V1) of normal adult vervet monkeys (Cercopithicus aethiops) to that in monkeys monocularly deprived of visual input for short (24 h) or long (3 months) survival times. In normal animals, staining levels for zinc were highest in layers 1-3, 4b, 5 and 6 and lowest in layers 4a and 4c. The laminar and tangential patterns of zinc staining were complementary to staining patterns demonstrated using cytochrome oxidase (CO) histochemistry. Following 3 months of monocular deprivation by enucleation, levels of zinc staining in layers 3, 4calpha and 6a were heterogeneously reduced, clearly revealing the ocular dominance pattern in V1. When compared with the pattern of CO staining, levels of both CO and zinc were reduced in cortical territory innervated by the enucleated eye. Zinc histochemistry also revealed the ocular dominance pattern after only 24 h of monocular impulse blockade induced by enucleation or intravitreal tetrodotoxin infusion. However, by either means of deprivation for 24 h, levels of zinc were increased in deprived-eye stripes relative to nondeprived-eye stripes. These results indicate that zincergic terminals demarcate distinct compartments in the primate visual cortex. Furthermore, levels of synaptic zinc are rapidly and dynamically regulated, suggesting that zinc and/or zincergic neurons participate in mediating activity-dependent changes in the organization of the adult neocortex.     

Evidence for cross-modal plasticity in adult mouse visual cortex following monocular enucleation

The goal of this study was to assess cortical reorganization in the visual system of adult mice in detail. A combination of deprivation of one eye and stimulation of the remaining eye previously led to the identification of input-specific subdivisions in mouse visual cortex. Using this information as a reference map, we established to what extent each of these functional subdivisions take part in cortical reactivation and reorganization upon unilateral enucleation. A recovery experiment revealed a differential laminar and temporal reactivation profile. Initiation of infragranular recovery of molecular activity near the border with nonvisual cortex and simultaneous hyperactivation of this adjacent cortex implied a partial nonvisual contribution to this plasticity. The strong effect of somatosensory deprivation as well as stimulation on infragranular visual cortex activation in long-term enucleated animals support this view. Furthermore, targeted tracer injections in visual cortex of control and enucleated animals revealed preexisting connections between the visual and somatosensory cortices of adult mice as possible mediators. In conclusion, this study supports an important cross-modal component in reorganization of adult mouse visual cortex upon monocular enucleation.     

Receptive fields in human visual cortex mapped with surface electrodes

Most of our understanding of the functional organization of human visual cortex comes from lesion and functional imaging studies and by extrapolation from results obtained by neuroanatomical and neurophysiological studies in nonhuman primates. Although some single-unit and field potential recordings have been made in human visual cortex, none has provided quantitative characterization of spatial receptive fields (RFs) of individual sites. Here we use subdural electrodes implanted for clinical purposes to quantitatively measure response properties in different regions of human visual cortex. We find significant differences in RF size, response latency, and response magnitude for sites in early visual areas, versus sites in later stages of both the dorsal and ventral streams. In addition, we use this technique to estimate the cortical magnification factor in early human visual cortex. The spatial and temporal resolution of cortical surface recordings suggest that this technique is well suited to examine further issues in visual processing in humans.     

Limited protection of the primary visual cortex from the effects of monocular deprivation by strabismus

Competition between the two eyes for synaptic space is thought to play a crucial role in the developmental plasticity of ocular dominance in the primary visual cortex. This competition should be disrupted if geniculocortical afferents from the two eyes are spatially segregated. In kittens, strabismus was induced in one eye before the onset of the critical period; the effects of a brief period of monocular deprivation (MD) at the height of the critical period and subsequent recovery were assessed in a longitudinal study employing optical imaging of intrinsic signals. Results were compared with those from a control group without strabismus. MD caused a substantial loss of cortical territory dominated by the deprived eye in all animals. However, in the strabismic animals this loss was smaller than in the control group for the hemisphere contralateral to the deprived eye. When the deprived eye was reopened, recovery of cortical territory was remarkably rapid in all kittens, and close to pre-deprivation responses were attained within 3-4 days of reopening. However, kittens without strabismus exhibited a greater rate of recovery from MD. Moreover, recovery of visual acuity, as assessed by visually evoked potential (VEP) measurements, was slower and less complete in animals with strabismus prior to MD. Therefore, strabismus does not provide lasting protection against the effects of MD.     

Opposite dependencies on visual motion coherence in human area MT+ and early visual cortex

In order to understand the relationship between brain activity and visual motion perception, knowledge of the cortical areas participating in signal processing alone is insufficient. Rather knowledge on how responses vary with the characteristics of visual motion is necessary. In this study, we measured whole brain activity using magnetoencephalography in humans discriminating the global motion direction of a random dot kinematogram whose strength was systematically varied by the percentage of coherently moving dot elements. Spectral analysis revealed 2 components correlating with motion coherence. A first component in the low-frequency domain ( approximately 3 Hz), linearly increasing with motion coherence, could be attributed to visual cortex including human area middle temporal (MT) +. A second component oscillating in the alpha frequency range and emerging after stimulus offset showed the inverse dependence on motion coherence and arose from early visual cortex. Based on these results, we first of all conclude that motion coherence is reflected in the population response of human extrastriate cortex. Second, we suggest that the occipital alpha activity represents a gating mechanism protecting visual motion integration in later cortical areas from disturbing upcoming signals.     

Spontaneous fluctuations in posterior alpha-band EEG activity reflect variability in excitability of human visual areas

Neural activity fluctuates dynamically with time, and these changes have been reported to be of behavioral significance, despite occurring spontaneously. Through electroencephalography (EEG), fluctuations in alpha-band (8-14 Hz) activity have been identified over posterior sites that covary on a trial-by-trial basis with whether an upcoming visual stimulus will be detected or not. These fluctuations are thought to index the momentary state of visual cortex excitability. Here, we tested this hypothesis by directly exciting human visual cortex via transcranial magnetic stimulation (TMS) to induce illusory visual percepts (phosphenes) in blindfolded participants, while simultaneously recording EEG. We found that identical TMS-stimuli evoked a percept (P-yes) or not (P-no) depending on prestimulus alpha-activity. Low prestimulus alpha-band power resulted in TMS reliably inducing phosphenes (P-yes trials), whereas high prestimulus alpha-values led the same TMS-stimuli failing to evoke a visual percept (P-no trials). Additional analyses indicated that the perceptually relevant fluctuations in alpha-activity/visual cortex excitability were spatially specific and occurred on a subsecond time scale in a recurrent pattern. Our data directly link momentary levels of posterior alpha-band activity to distinct states of visual cortex excitability, and suggest that their spontaneous fluctuation constitutes a visual operation mode that is activated automatically even without retinal input.     

Prenatal development of calbindin D-28K in human visual cortex

The distribution of the calcium-binding protein calbindin D-28K (CB) was investigated in human fetal primary visual cortex. CB is present in Cajal-Retzius cells of layer I, in sparse neurons of the ventricular and intermediate zones (VZ, IZ), and in tangential fibres in IZ by 15 weeks (W) of gestation. Cajal-Retzius cells lose their staining by 30W. CB appears in layers II-VI mainly from 26W, following an inside-outside sequence. Until 34W, CB labelling is in somata and neuropil located primarily in layers IVA, IVC and V. Then reactive perikarya and puncta increase in layers II-IVA and deep IVB and C, but are reduced in infragranular layers from 34W to term. From 30W positive somata form clusters in the cell-rich bands in layers IV and V and labelled neuropil in layers III and IV has a periodic pattern from 34W. Also from 34W, numerous lightly reactive pyramidal cells are present in layers II to IVA in primary, but not secondary, visual cortex. Our results show precocious expression of CB before full laminar differentiation of the cortex and that some of this expression is transient.      

Spatial attention modulates initial afferent activity in human primary visual cortex

It is well established that spatially directed attention enhances visual perceptual processing. However, the earliest level at which processing can be affected remains unknown. To date, there has been no report of modulation of the earliest visual event-related potential component "C1" in humans, which indexes initial afference in primary visual cortex (V1). Thus it has been suggested that initial V1 activity is impenetrable, and that the earliest modulations occur in extrastriate cortex. However, the C1 is highly variable across individuals, to the extent that uniform measurement across a group may poorly reflect the dynamics of V1 activity. In the present study we employed an individualized mapping procedure to control for such variability. Parameters for optimal C1 measurement were determined in an independent, preliminary "probe" session and later applied in a follow-up session involving a spatial cueing task. In the spatial task, subjects were cued on each trial to direct attention toward 1 of 2 locations in anticipation of an imperative Gabor stimulus and were required to detect a region of lower luminance appearing within the Gabor pattern 30% of the time at the cued location only. Our data show robust spatial attentional enhancement of the C1, beginning as early as its point of onset (57 ms). Source analysis of the attentional modulations points to generation in striate cortex. This finding demonstrates that at the very moment that visual information first arrives in cortex, it is already being shaped by the brain's attentional biases.     

Meperidine suppresses the excitability of spinal dorsal horn neurons

BACKGROUND: In addition to local anesthetics, meperidine has been successfully used for local anesthesia. When applied intrathecally, the dorsal horn neurons of the superficial laminae are exposed to high concentrations of meperidine. These cells represent an important point for the transmission of pain information. This study investigated the blocking effects of meperidine on different ionic currents of spinal dorsal horn neurons and, in particular, its impact on the generation of action potentials. METHODS: Using a combination of the patch clamp technique and the entire soma isolation method, the action of meperidine on voltage-gated Na+ and K+ currents in spinal dorsal horn neurons of rats was described. Current clamp recordings from intact neurons showed the functional relevance of the ion current blockade for the generation of action potentials. RESULTS: Externally applied meperidine reversibly blocked voltage-gated Na+ currents with a half-maximum inhibiting concentration (IC50) of 112 microM. During repetitive stimulation, a slight phasic block occurred. In addition, A-type K+ currents and delayed-rectifier K+ currents were affected in a dose-dependent manner, with IC50 values of 102 and 52 microM, respectively. In the current clamp mode, single action potentials were suppressed by meperidine. The firing frequency was lowered to 54% at concentrations (100 microM) insufficient for the suppression of a single action potential. CONCLUSIONS: Meperidine inhibits the complex mechanism of generating action potentials in spinal dorsal horn neurons by the blockade of voltage-gated Na+ and K+ channels. This can contribute to the local anesthetic effect of meperidine during spinal anesthesia.     

The intrinsic shape of human and macaque primary visual cortex

Previous studies have reported considerable variability in primary visual cortex (V1) shape in both humans and macaques. Here, we demonstrate that much of this variability is due to the pattern of cortical folds particular to an individual and that V1 shape is similar among individual humans and macaques as well as between these 2 species. Human V1 was imaged ex vivo using high-resolution (200 microm) magnetic resonance imaging at 7 T. Macaque V1 was identified in published histological serial section data. Manual tracings of the stria of Gennari were used to construct a V1 surface, which was computationally flattened with minimal metric distortion of the cortical surface. Accurate flattening allowed investigation of intrinsic geometric features of cortex, which are largely independent of the highly variable cortical folds. The intrinsic shape of V1 was found to be similar across human subjects using both nonparametric boundary matching and a simple elliptical shape model fit to the data and is very close to that of the macaque monkey. This result agrees with predictions derived from current models of V1 topography. In addition, V1 shape similarity suggests that similar developmental mechanisms are responsible for establishing V1 shape in these 2 species.     

Organizational principles of human visual cortex revealed by receptor mapping

This receptorarchitectonic study of the human visual cortex investigated interareal differences in mean receptor concentrations and laminar distribution patterns of 16 neurotransmitter receptors in the dorsal and ventral parts of areas V1, V2, V3 as well as in adjoining areas V4 (ventrally) and V3A (dorsally). Both the functional hierarchy of these areas and a distinction between dorsal and ventral visual cortices were reflected by significant receptorarchitectonic differences. The observation that dorso-ventral differences existed in all extrastriate areas (including V2) is particularly important for the discussion about the relationship between dorsal and ventral V3 as it indicates that a receptorarchitectonic distinction between the ventral and dorsal visual cortices is present in but not specific to V3. This molecular specificity is mirrored by previously reported differences in retinal microstructure and functional differences as revealed in behavioral experiments demonstrating differential advantages for stimulus processing in the upper and lower visual fields. We argue that these anatomical and functional differences may be regarded as the result of an evolutionary optimization adapting to the processing of the most relevant stimuli occurring in the upper and lower visual fields.     

Domain specificity in visual cortex

We investigated the prevalence and specificity of category-selective regions in human visual cortex. In the broadest survey to date of category selectivity in visual cortex, 12 participants were scanned with functional magnetic resonance imaging while viewing scenes and 19 different object categories in a blocked-design experiment. As expected, we found selectivity for faces in the fusiform face area (FFA), for scenes in the parahippocampal place area (PPA), and for bodies in the extrastriate body area (EBA). In addition, we describe 3 main new findings. First, evidence for the selectivity of the FFA, PPA, and EBA was strengthened by the finding that each area responded significantly more strongly to its preferred category than to the next most effective of the remaining 19 stimulus categories tested. Second, a region in the middle temporal gyrus that has been reported to respond significantly more strongly to tools than to animals did not respond significantly more strongly to tools than to other nontool categories (such as fruits and vegetables), casting doubt on the characterization of this region as tool selective. Finally, we did not find any new regions in the occipitotemporal pathway that were strongly selective for other categories. Taken together, these results demonstrate both the strong selectivity of a small number of regions and the scarcity of such regions in visual cortex.     

Cytochrome oxidase and neurofilament reactivity in monocularly deprived human primary visual cortex

Previous studies of human primary visual cortex (V1) have demonstrated a significant eye-specific decrease in cytochrome oxidase (CO) staining following monocular enucleation. We have extended these results by examining CO staining and neurofilament labeling in V1 from a patient with long-standing monocular blindness. A pattern of reduced neurofilament reactivity was found to align with pale CO-stained ocular dominance columns. Neurons located within deprived ocular dominance columns were significantly smaller compared with those in nondeprived columns. A spatial analysis of the relationship between CO blobs and ocular dominance columns revealed that both deprived and nondeprived blobs tended to align with the centers of ocular dominance columns.     

A comparison of visual and auditory motion processing in human cerebral cortex

Visual and auditory motion information can be used together to provide complementary information about the movement of objects. To investigate the neural substrates of such cross-modal integration, functional magnetic resonance imaging was used to assess brain activation while subjects performed separate visual and auditory motion discrimination tasks. Areas of unimodal activation included the primary and/or early sensory cortex for each modality plus additional sites extending toward parietal cortex. Areas conjointly activated by both tasks included lateral parietal cortex, lateral frontal cortex, anterior midline and anterior insular cortex. The parietal site encompassed distinct, but partially overlapping, zones of activation in or near the intraparietal sulcus (IPS). A subsequent task requiring an explicit cross-modal speed comparison revealed several foci of enhanced activity relative to the unimodal tasks. These included the IPS, anterior midline, and anterior insula but not frontal cortex. During the unimodal auditory motion task, portions of the dorsal visual motion system showed signals depressed below resting baseline. Thus, interactions between the two systems involved either enhancement or suppression depending on the stimuli present and the nature of the perceptual task. Together, these results identify human cortical regions involved in polysensory integration and the attentional selection of cross-modal motion information.     

Columnar organization of the mammalian visual cortex and its vulnerability following lesion in adult cats

It is well known that in the mammalian visual cortex the neurons, sharing similar response properties, are grouped together into functional units, known as cortical columns. The orientation and ocular dominance columnar organization is a fundamental element for both the anatomical and physiological features of the visual cortex. Nonetheless, little is known about the functional restoration of matured columnar columns following injury. In the present study, the visual cortex of adult cats was studied electrophysiologically, whereas the primary goal of the study was to reveal the functional stability of the columns, disconnected from the main visual input. Experiments were performed on the primary visual cortex (area 17) of 13 anaesthetized and paralyzed adult cats. The columnar distortion was produced by surgical incision perpendicular to the cortical columns. The single unit activity was recorded from 1186 visual cells (experimental groups) in areas proximal and distal to the lesion and, compared to data, received from intact visual cortex (control group). The results indicate that most of the visually responsive cells were found to be selective to specific orientation in all experimental groups (75-100%) similar to the normal control group (78%). Moreover, the distribution of orientation-specific cells was very similar in all experimental and control groups (p > 0.05), as well as in both recording areas (p > 0.05). The percentage of binocular cells was significantly lower in all experimental groups (23-49%) in comparison to the control (80%). However, the distribution of the binocular cells revealed the significant similarity between the experimental and control groups (p > 0.05). An additional finding of the study is that the visual responsiveness of cells was significantly reduced in all experimental groups: only 28-49% of cells were found to be responsive following injury, as compared to 86% in normal control group (p < 0.001). The distribution of cells has also been analysed in accordance with their directional specificity and it has been found that the majority of cells in the experimental groups were found to be bias and non-specific to light stimuli (52-84%) as compared normal controls (21%) (p < 0.001). It has been concluded that, despite the fact that no improvement in visual function was found, the inherent structure of the disrupted cortical columns in the visual cortex was generally preserved. Therefore, the disruption of the columnar connection does not lead to remarkable distortion of the connectivity pattern on the whole, though it does reduce the responsiveness level there. It was concluded that the columnar structure for both orientation and ocular dominance is characterized by high stability, which enables visual processing with minimal brain connections.