Formation of mnemonic neuronal responses to visual paired associates in inferotemporal cortex is impaired by perirhinal and entorhinal lesions.

Functional roles of the cortical backward signal in long-term memory formation were studied in monkeys performing a visual pair-association task. Before the monkeys learned the task, the anterior commissure was transected, disconnecting the anterior temporal cortex of each hemisphere. After training with 12 pairs of pictures, single units were recorded from the inferotemporal cortex of the monkeys as the control. By injecting a grid of ibotenic acid, we unilaterally lesioned the entorhinal and perirhinal cortex, which provides massive direct and indirect backward projections ipsilaterally to the inferotemporal cortex. After the lesion, the monkeys fixated the cue stimulus normally, relearned the preoperatively learned set (set A), and learned a new set (set B) of paired associates. Then, single units were recorded from the same area as for the prelesion control. We found that (i) in spite of the lesion, the sampled neurons responded strongly and selectively to both the set A and set B patterns and (ii) the paired associates elicited significantly correlated responses in the control neurons before the lesion but not in the cells tested after the lesion, either for set A or set B stimuli. We conclude that the ability of inferotemporal neurons to represent association between picture pairs was lost after the lesion of entorhinal and perirhinal cortex, most likely through disruption of backward neural signals to the inferotemporal neurons, while the ability of the neurons to respond to a particular visual stimulus was left intact.

Learning and recall of form discriminations during reversible cooling deactivation of ventral-posterior suprasylvian cortex in the cat.

Extrastriate visual cortex of the ventral-posterior suprasylvian gyrus (vPS cortex) of freely behaving cats was reversibly deactivated with cooling to determine its role in performance on a battery of simple or masked two-dimensional pattern discriminations, and three-dimensional object discriminations. Deactivation of vPS cortex by cooling profoundly impaired the ability of the cats to recall the difference between all previously learned pattern and object discriminations. However, the cats' ability to learn or relearn pattern and object discriminations while vPS was deactivated depended upon the nature of the pattern or object and the cats' prior level of exposure to them. During cooling of vPS cortex, the cats could neither learn the novel object discriminations nor relearn a highly familiar masked or partially occluded pattern discrimination, although they could relearn both the highly familiar object and simple pattern discriminations. These cooling-induced deficits resemble those induced by cooling of the topologically equivalent inferotemporal cortex of monkeys and provides evidence that the equivalent regions contribute to visual processing in similar ways.

The temporal lobe is a target of output from the basal ganglia.

The basal ganglia are known to receive inputs from widespread regions of the cerebral cortex, such as the frontal, parietal, and temporal lobes. Of these cortical areas, only the frontal lobe is thought to be the target of basal ganglia output. One of the cortical regions that is a source of input to the basal ganglia is area TE, in inferotemporal cortex. This cortical area is thought to be critically involved in the recognition and discrimination of visual objects. Using retrograde transneuronal transport of herpes simplex virus type 1, we have found that one of the output nuclei of the basal ganglia, the substantia nigra pars reticulata, projects via the thalamus to TE. Thus, TE is not only a source of input to the basal ganglia, but also is a target of basal ganglia output. This result implies that the output of the basal ganglia influences higher order aspects of visual processing. In addition, we propose that dysfunction of the basal ganglia loop with TE leads to alterations in visual perception, including visual hallucinations.

Activity of primate inferotemporal neurons related to a sought target in pair-association task.

Visual long-term memory in primates has been assessed by using the pair-association (PA) task, in which a subject retrieves and chooses the paired associate of a cue picture. Our previous studies on single neurons in the anterior inferotemporal (AIT) cortex suggested their roles in representing paired associates in the mind. To test the possibility that the delay activity of AIT neurons is related to a particular picture as a sought target, we devised the PA with color switch (PACS) task. In the PACS task, the necessity for memory retrieval and its initiation time were controlled by a color switch in the middle of the delay period. A control task, in which there is no color switch, corresponds to the conventional delayed matching-to-sample (DMS) task where the monkey chooses the same picture as a cue. We found that AIT neurons started to respond just after the color switch in the PACS task, when the cue-optimal picture's associate was presented as a cue. In contrast, they showed no response change in the DMS task. We confirmed that this effect is not due to the visual response to colors. Furthermore, when the cue-optimal picture was presented as a cue, these neurons showed suppression after the color switch in the PACS task. These results suggest that the activity of AIT neurons mediates gating mechanisms that preferentially pass information about a sought target, even when the sought target is retrieved from long-term memory.

Optical imaging of functional domains in the cortex of the awake and behaving monkey

As demonstrated by anatomical and physiological studies, the cerebral cortex consists of groups of cortical modules, each comprising populations of neurons with similar functional properties. This functional modularity exists in both sensory and association neocortices. However, the role of such cortical modules in perceptual and cognitive behavior is unknown. To aid in the examination of this issue we have applied the high spatial resolution optical imaging methodology to the study of awake, behaving animals. In this paper, we report the optical imaging of orientation domains and blob structures, approximately 100–200 μm in size, in visual cortex of the awake and behaving monkey. By overcoming the spatial limitations of other existing imaging methods, optical imaging will permit the study of a wide variety of cortical functions at the columnar level, including motor and cognitive functions traditionally studied with positron-emission tomography or functional MRI techniques.

Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex

The present study used functional magnetic resonance imaging to demonstrate that performance of visual spatial and visual nonspatial working memory tasks involve the same regions of the lateral prefrontal cortex when all factors unrelated to the type of stimulus material are appropriately controlled. These results provide evidence that spatial and nonspatial working memory may not be mediated, respectively, by mid-dorsolateral and mid-ventrolateral regions of the frontal lobe, as widely assumed, and support the alternative notion that specific regions of the lateral prefrontal cortex make identical executive functional contributions to both spatial and nonspatial working memory.

Synchronization between prefrontal and posterior association cortex during human working memory

We measured coherence between the electroencephalogram at different scalp sites while human subjects performed delayed response tasks. The tasks required the retention of either verbalizable strings of characters or abstract line drawings. In both types of tasks, a significant enhancement in coherence in the θ range (4–7 Hz) was found between prefrontal and posterior electrodes during 4-s retention intervals. During 6-s perception intervals, far fewer increases in θ coherence were found. Also in other frequency bands, coherence increased; however, the patterns of enhancement made a relevance for working memory processes seem unlikely. Our results suggest that working memory involves synchronization between prefrontal and posterior association cortex by phase-locked, low frequency (4–7 Hz) brain activity.

Bidirectional, experience-dependent regulation of N-methyl-d-aspartate receptor subunit composition in the rat visual cortex during postnatal development

In the visual cortex, as elsewhere, N-methyl-d-aspartate receptors (NMDARs) play a critical role in triggering long-term, experience-dependent synaptic plasticity. Modifications of NMDAR subunit composition alter receptor function, and could have a large impact on the properties of synaptic plasticity. We have used immunoblot analysis to investigate the effects of age and visual experience on the expression of different NMDAR subunits in synaptoneurosomes prepared from rat visual cortices. NMDARs at birth are comprised of NR2B and NR1 subunits, and, over the first 5 postnatal weeks, there is a progressive inclusion of the NR2A subunit. Dark rearing from birth attenuates the developmental increase in NR2A. Levels of NR2A increase rapidly (in <2 hr) when dark-reared animals are exposed to light, and decrease gradually over the course of 3 to 4 days when animals are deprived of light. These data reveal that NMDAR subunit composition in the visual cortex is remarkably dynamic and bidirectionally regulated by sensory experience. We propose that NMDAR subunit regulation is a mechanism for experience-dependent modulation of synaptic plasticity in the visual cortex, and serves to maintain synaptic strength within an optimal dynamic range.

Excitatory–inhibitory network in the visual cortex: Psychophysical evidence

At early stages in visual processing cells respond to local stimuli with specific features such as orientation and spatial frequency. Although the receptive fields of these cells have been thought to be local and independent, recent physiological and psychophysical evidence has accumulated, indicating that the cells participate in a rich network of local connections. Thus, these local processing units can integrate information over much larger parts of the visual field; the pattern of their response to a stimulus apparently depends on the context presented. To explore the pattern of lateral interactions in human visual cortex under different context conditions we used a novel chain lateral masking detection paradigm, in which human observers performed a detection task in the presence of different length chains of high-contrast-flanked Gabor signals. The results indicated a nonmonotonic relation of the detection threshold with the number of flankers. Remote flankers had a stronger effect on target detection when the space between them was filled with other flankers, indicating that the detection threshold is caused by dynamics of large neuronal populations in the neocortex, with a major interplay between excitation and inhibition. We considered a model of the primary visual cortex as a network consisting of excitatory and inhibitory cell populations, with both short- and long-range interactions. The model exhibited a behavior similar to the experimental results throughout a range of parameters. Experimental and modeling results indicated that long-range connections play an important role in visual perception, possibly mediating the effects of context.

Glial reduction in the subgenual prefrontal cortex in mood disorders

Mood disorders are among the most common neuropsychiatric illnesses, yet little is known about their neurobiology. Recent neuroimaging studies have found that the volume of the subgenual part of Brodmann’s area 24 (sg24) is reduced in familial forms of major depressive disorder (MDD) and bipolar disorder (BD). In this histological study, we used unbiased stereological techniques to examine the cellular composition of area sg24 in two different sets of brains. There was no change in the number or size of neurons in area sg24 in mood disorders. In contrast, the numbers of glia were reduced markedly in both MDD and BD. The reduction in glial number was most prominent in subgroups of subjects with familial MDD (24%, P = 0.01) or BD (41%, P = 0.01). The glial reduction in subjects without a clear family history was lower in magnitude and not statistically significant. Consistent with neuroimaging findings, cortical volume was reduced in area sg24 in subjects with familial mood disorders. Schizophrenic brains studied as psychiatric controls had normal neuronal and glial numbers and cortical volume. Glial and neuronal numbers also were counted in area 3b of the somatosensory cortex in the same group of brains and were normal in all psychiatric groups. Glia affect several processes, including regulation of extracellular potassium, glucose storage and metabolism, and glutamate uptake, all of which are crucial for normal neuronal activity. We thus have identified a biological marker associated with familial mood disorders that may provide important clues regarding the pathogenesis of these common psychiatric conditions.

Visual stimuli induce waves of electrical activity in turtle cortex

The computations involved in the processing of a visual scene invariably involve the interactions among neurons throughout all of visual cortex. One hypothesis is that the timing of neuronal activity, as well as the amplitude of activity, provides a means to encode features of objects. The experimental data from studies on cat [Gray, C. M., Konig, P., Engel, A. K. & Singer, W. (1989) Nature (London) 338, 334–337] support a view in which only synchronous (no phase lags) activity carries information about the visual scene. In contrast, theoretical studies suggest, on the one hand, the utility of multiple phases within a population of neurons as a means to encode independent visual features and, on the other hand, the likely existence of timing differences solely on the basis of network dynamics. Here we use widefield imaging in conjunction with voltage-sensitive dyes to record electrical activity from the virtually intact, unanesthetized turtle brain. Our data consist of single-trial measurements. We analyze our data in the frequency domain to isolate coherent events that lie in different frequency bands. Low frequency oscillations (<5 Hz) are seen in both ongoing activity and activity induced by visual stimuli. These oscillations propagate parallel to the afferent input. Higher frequency activity, with spectral peaks near 10 and 20 Hz, is seen solely in response to stimulation. This activity consists of plane waves and spiral-like waves, as well as more complex patterns. The plane waves have an average phase gradient of ≈π/2 radians/mm and propagate orthogonally to the low frequency waves. Our results show that large-scale differences in neuronal timing are present and persistent during visual processing.

Brain activity in visual cortex predicts individual differences in reading performance

The relationship between brain activity and reading performance was examined to test the hypothesis that dyslexia involves a deficit in a specific visual pathway known as the magnocellular (M) pathway. Functional magnetic resonance imaging was used to measure brain activity in dyslexic and control subjects in conditions designed to preferentially stimulate the M pathway. Dyslexics showed reduced activity compared with controls both in the primary visual cortex and in a secondary cortical visual area (MT+) that is believed to receive a strong M pathway input. Most importantly, significant correlations were found between individual differences in reading rate and brain activity. These results support the hypothesis for an M pathway abnormality in dyslexia and imply a strong relationship between the integrity of the M pathway and reading ability.

Inputs to directionally selective simple cells in macaque striate cortex

It is clear that the initial analysis of visual motion takes place in the striate cortex, where directionally selective cells are found that respond to local motion in one direction but not in the opposite direction. Widely accepted motion models postulate as inputs to directional units two or more cells whose spatio-temporal receptive fields (RFs) are approximately 90° out of phase (quadrature) in space and in time. Simple cells in macaque striate cortex differ in their spatial phases, but evidence is lacking for the varying time delays required for two inputs to be in temporal quadrature. We examined the space-time RF structure of cells in macaque striate cortex and found two subpopulations of (nondirectional) simple cells, some that show strongly biphasic temporal responses, and others that are weakly biphasic if at all. The temporal impulse responses of these two classes of cells are very close to 90° apart, with the strongly biphasic cells having a shorter latency than the weakly biphasic cells. A principal component analysis of the spatio-temporal RFs of directionally selective simple cells shows that their RFs could be produced by a linear combination of two components; these two components correspond closely in their respective latencies and biphasic characters to those of strongly biphasic and weakly biphasic nondirectional simple cells, respectively. This finding suggests that the motion system might acquire the requisite temporal quadrature by combining inputs from these two classes of nondirectional cells (or from their respective lateral geniculate inputs, which appear to be from magno and parvo lateral geniculate cells, respectively).

Memory fields of neurons in the primate prefrontal cortex

Many prefrontal (PF) neurons convey information about both an object’s identity (what) and its location (where). To explore how they represent conjunctions of what and where, we explored the receptive fields of their mnemonic activity (i.e., their “memory fields”) by requiring monkeys to remember both an object and its location at many positions throughout a wide portion of central vision. Many PF neurons conveyed object information and had highly localized memory fields that emphasized the contralateral, but not necessarily foveal, visual field. These results indicate that PF neurons can simultaneously convey precise location and object information and thus may play a role in constructing a unified representation of a visual scene.

Patches of synchronized activity in the cerebellar cortex evoked by mossy-fiber stimulation: Questioning the role of parallel fibers

The discrepancy between the structural longitudinal organization of the parallel-fiber system in the cerebellar cortex and the functional mosaic-like organization of the cortex has provoked controversial theories about the flow of information in the cerebellum. We address this issue by characterizing the spatiotemporal organization of neuronal activity in the cerebellar cortex by using optical imaging of voltage-sensitive dyes in isolated guinea-pig cerebellum. Parallel-fiber stimulation evoked a narrow beam of activity, which propagated along the parallel fibers. Stimulation of the mossy fibers elicited a circular, nonpropagating patch of synchronized activity. These results strongly support the hypothesis that a beam of parallel fibers, activated by a focal group of granule cells, fails to activate the Purkinje cells along most of its length. It is thus the ascending axon of the granule cell, and not its parallel branches, that activates and defines the basic functional modules of the cerebellar cortex.