Sensory Afferent Projections and Area 3b Somatotopy following Median Nerve Cut and Repair in Macaque Monkeys

The fidelity of median nerve regeneration and the consequenteffects of regeneration errors on cortical organization weredetermined in combined anatomical and electrophysiological studies.In three adult macaque monkeys, the median nerve was cut, sutured,and allowed to regenerate for 7–13 months. After regeneration,distributions of afferents to the dorsal horn of the spinalcord and the cuneate nucleus of the brainstem were determinedby making injections of horseradish peroxidase conjugates intothe distal phalanges of digit 1 or 2. While label from a singledigit on the normal hand was confined to the appropriate locationsin the median nerve territories of the dorsal horn and cuneatenucleus, label from the reinnervated digits spread out to covermost of the median nerve territories in those structures. Theseresults are consistent with the interpretation that some proportionof primary sensory fibers normally innervating other digitsand pads of median nerve skin erroneously reinnervated the skinof the injacted digits. In the same monkeys, microelectrodeswere used to record from an array of closely spaced sites acrossthe representation of the hand in area 3b of somatosensory cortex.The reactivation pattern was abnormal, with neurons at manyrecording sites having more than one receptive field, largerthan normal receptive fields, or receptive fields at abnormalskin locations. Thus, there is somatotopic disorder both inthe regenerated median nerve and in reactivated cortex, indicatingthat primary somatosensory cortex does not reorganize to compansatefully for peripheral reinnervation errors in these adult primates.Nevertheless, the organization of receptive fields in area 3bsuggests the existence of some central selection of synapses.     

Neuronal responses to optic flow in the monkey parietal area PEc

Area PEc, a high order association area, is located in the dorsocaudal portion of the superior parietal cortex. PEc neurons encode visual motion signals, especially the direction of stimulus motion. The present study tested if PEc neurons also process visual correlates of self-motion. The extracellular activity of single neurons in response to optic flow stimuli was recorded in two monkeys (Macaca fascicularis) trained in a fixation task. The stimuli were produced by random dots simulating planar motion, radial expansion and radial contraction. A substantial number of PEc neurons were specifically activated by radial optic flow and were selective for the position of the focus of expansion with respect to the fovea. Eccentric positions of the focus of expansion were preferred. Almost all neurons showed opponent excitatory-inhibitory activity to expanding-contracting visual fields. Planar motion elicited very weak responses. Optic flow responsiveness is not entirely explained by classical bar sensitivity in PEc neurons, suggesting that optic flow and classical bar responses could serve different mechanisms in the integration of visuo-motor signals to prepare body movements.     

Eye-hand coordination during reaching. II. An analysis of the relationships between visuomanual signals in parietal cortex and parieto-frontal association projections

The relationships between the distribution of visuomanual signals in parietal cortex and that of parieto-frontal projections are the subject of the present study. Single cell recording was performed in areas PEc and V6A, where different anatomical tracers were also injected. The monkeys performed a variety of behavioral tasks, aimed at studying the visual and motor properties of parietal cells, as well as the potential combination of retinal-, eye- and hand-related signals on cell activity. The activity of most cells was related to the direction of movement and the active position of the hand. Many of these reach-related cells were influenced by eye position information. Fewer cells displayed relationships to saccadic eye movements. The activity of most neurons related to a combination of both hand and eye signals. Many cells were also modulated during preparation for hand movement. Light-dark differences of activity were common and interpreted as related to the sight and monitoring of hand motion and/or position in the visual field. Most cells studied were very sensitive to moving visual stimuli and also responded to optic flow stimulation. Visual receptive fields were generally large and extended to the periphery of the visual field. For most neurons, the orientation of the preferred directions computed across different epochs and tasks conditions clustered within a limited sector of space, the field of global tuning. This can be regarded as an ideal frame to combine spatially congruent eye- and hand-related information for different forms of visuomanual behavior. All these properties were common to both PEc and V6A. Retinal, eye- and hand-related activity types, as well as parieto-frontal association cells, were distributed in a periodic fashion across the tangential domain of areas PEc and V6A. These functional and anatomical distributions were characterized and compared through a spectral and coherency analysis, which revealed the existence of a selective 'match' between activity types and parieto-frontal connections. This match depended on where each individual efferent projection was addressed. The results of the present and of the companion study can be relevant for a re-interpretation of optic ataxia as the consequence of the breakdown of the combination of retinal-, eye- and hand-related directional signals within the global tuning fields of parietal neurons.     

The organization and connections of anterior and posterior parietal cortex in titi monkeys: do New World monkeys have an area 2?

We used multiunit electrophysiological recording techniques to examine the topographic organization of somatosensory area 3b and cortex posterior to area 3b, including area 1 and the presumptive area 5, in the New World titi monkey, Callicebus moloch. We also examined the ipsilateral and contralateral connections of these fields, as well as those in a region of cortex that appeared to be similar to both area 7b and the anterior intraparietal area (7b/AIP) described in macaque monkeys. All data were combined with architectonic analysis to generate comprehensive reconstructions. These studies led to several observations. First, area 1 in titi monkeys is not as precisely organized in terms of topographic order and receptive field size as is area 1 in macaque monkeys and a few New World monkeys. Second, cortex caudal to area 1 in titi monkeys is dominated by the representation of the hand and forelimb, and contains neurons that are often responsive to visual stimulation as well as somatic stimulation. This organization is more like area 5 described in macaque monkeys than like area 2. Third, ipsilateral and contralateral cortical connections become more broadly distributed away from area 3b towards the posterior parietal cortex. Specifically, area 3b has a relatively restricted pattern of connectivity with adjacent somatosensory fields 3a, 1, S2 and PV; area 1 has more broadly distributed connections than area 3b; and the presumptive areas 5 and 7b/AIP have highly diverse connections, including connections with motor and premotor cortex, extrastriate visual areas, auditory areas and somatosensory areas of the lateral sulcus. Fourth, the hand representation of the presumptive area 5 has dense callosal connections. Our results, together with previous studies in other primates, suggest that anterior parietal cortex has expanded in some primate lineages, perhaps in relation to manual abilities, and that the region of cortex we term area 5 is involved in integrating somatic inputs with the motor system and across hemispheres. Such connections could form the substrate for intentional reaching, grasping and intermanual transfer of information necessary for bilateral coordination of the hands.     

Neural activity profiles of the neocortex and superior colliculus after bimodal sensory stimulation.

Current efforts at functional mapping of multisensory neurons are hampered by the need for both cellular-level resolution and the separate visualization of activity by different sensory cues. We have used a recently developed technique that exploits the differential time course of zif268 mRNA versus protein induction in neurons after sensory stimulation. Adult male rats were visually and acoustically deprived and then exposed to one of the following stimulation sequences: (i) no sensory stimulation; (ii) 2 h visual stimulation followed by 30 min auditory stimulation; (iii) 2 h auditory stimulation followed 30 min of visual stimulation; and (iv) 2 h compound visual and auditory stimulation. The neocortex and superior colliculus (SC) were then processed for fluorescent immunocytochemistry and in situ hybridization for staining of Zif268 protein and mRNA products. We have found that activity patterns in primary visual and auditory cortices were in accord with the sequence of the compound stimulus. We also show that SC superficial layers contained a pool of exclusively unimodal neurons, similar to that of visual cortex. Activity patterns of deep SC layers contained multimodal neurons with varying degrees of visual and auditory convergence. The deep SC layers also showed that auditory processing was largely carried out by a small, bimodal group of neurons whereas visual processing was coordinated by both a large unimodal and a small bimodal pool of neurons.     

Do cross-modal projections always result in multisensory integration?

Convergence of afferents from different sensory modalities has generally been thought to produce bimodal (and trimodal) neurons (i.e., exhibit suprathreshold excitation to more than 1 sensory modality). Consequently, studies identifying cross-modal connections assume that such convergence results in bimodal (or trimodal) neurons that produce familiar forms of multisensory integration: response enhancement or depression. The present study questioned that assumption by anatomically identifying a projection from ferret auditory to visual cortex Area 21. However, electrophysiological recording within Area 21 not only failed to identify a single bimodal neuron but also familiar forms of multisensory integration were not observed either. Instead, a small proportion of neurons (9%; 27/296) showed subthreshold multisensory integration, in which visual responses were significantly modulated by auditory inputs. Such subthreshold multisensory effects were enhanced by gamma-aminobutyric acid antagonism, whereby a majority of neurons (87%; 20/23) now participated in a significant, multisensory population effect. Thus, multisensory convergence does not de facto result in bimodal (or trimodal) neurons or the traditional forms of multisensory integration. However, the fact that unimodal neurons exhibited a subthreshold form of multisensory integration not only affirms the relationship between convergence and integration but also expands our understanding of the functional repertoire of multisensory processing itself.     

Estimating receptive field size from fMRI data in human striate and extrastriate visual cortex.

Functional magnetic resonance imaging (fMRI) was used to estimate the average receptive field sizes of neurons in each of several striate and extrastriate visual areas of the human cerebral cortex. The boundaries of the visual areas were determined by retinotopic mapping procedures and were visualized on flattened representations of the occipital cortex. Estimates of receptive field size were derived from the temporal duration of the functional activation at each cortical location as a visual stimulus passed through the receptive fields represented at that location. Receptive fields are smallest in the primary visual cortex (V1). They are larger in V2, larger again in V3/VP and largest of all in areas V3A and V4. In all these areas, receptive fields increase in size with increasing stimulus eccentricity. The results are qualitatively in line with those obtained by others in macaque monkeys using neurophysiological methods.     

Hierarchical development of the primate visual cortex, as revealed by neurofilament immunoreactivity: early maturation of the middle temporal area (MT)

It has been suggested that the development of the cerebral cortex reflects its hierarchical organization, with the primary sensory areas being the first to reach structural and functional maturity, and higher-order association areas being the last. In the present study, we labelled the cortex of New World marmoset monkeys of late fetal and early postnatal ages with an antibody to non-phosphorylated neurofilament, a marker of structural maturation of a subset of pyramidal cells. Supporting the concept of hierarchical maturation, we found that at birth labelled cells were found in the primary visual, auditory and somatosensory areas, but not in most other cortical fields. The exception was visual area MT, which revealed an infragranular pattern of labelling comparable to the one observed in the primary areas, as well as some supragranular staining. In MT, an adult-like pattern of labelled cells, including both supragranular and infragranular layer neurons, emerged within the first postnatal month. In comparison, the development of other extrastriate areas was delayed, with the first signs of neurofilament staining not present until the third week. The present results support the concept of MT as another primary visual area, an idea previously advanced on the basis of functional and anatomical evidence.     

Topographic Maps within Brodmann's Area 5 of macaque monkeys

Brodmann's area 5 has traditionally included the rostral bank of the intraparietal sulcus (IPS) as well as posterior portions of the postcentral gyrus and medial wall. However, different portions of this large architectonic zone may serve different functions related to reaching and grasping behaviors. The current study used multiunit recording techniques in anesthetized macaque monkeys to survey a large extent of the rostral bank of the IPS so that hundreds of recording sites could be used to determine the functional subdivisions and topographic organization of cortical areas in this region. We identified a lateral area on the rostral IPS that we term area 5L. Area 5L contains neurons with receptive fields on mostly the shoulder, forelimb, and digits, with no apparent representation of other body parts. Thus, there is a large magnification of the forelimb. Receptive fields for neurons in this region often contain multiple joints of the forelimb or multiple digits, which results in imprecise topography or fractures in map organization. Our results provide the first overall topographic map of area 5L obtained in individual macaque monkeys and suggest that this region is distinct from more medial portions of the IPS.     

Movement-related neurons of the subthalamic nucleus in patients with Parkinson disease

OBJECT: The subthalamic nucleus (STN) is a target in the surgical treatment of Parkinson disease (PD). Little is known about the neurons within the human STN that modulate movement. The authors' goal was to examine the distribution of movement-related neurons within the STN of humans by using microelectrode recording to identify neuronal receptive fields. METHODS: Data were retrospectively collected from microelectrode recordings that had been obtained in 38 patients with PD during surgery for placement of STN deep brain stimulation electrodes. The recordings had been obtained in awake, nonsedated patients. Antiparkinsonian medications were withheld the night before surgery. Neuronal discharges were amplified, filtered, and displayed on an oscilloscope and fed to an audio monitor. The receptive fields were identified by the presence of reproducible, audible changes in the firing rate that were time-locked to the movement of specific joint(s). The median number of electrode tracks per patient was six (range two-nine). The receptive fields were identified in 278 (55%) of 510 STN neurons studied. One hundred one tracks yielded receptive field data. Fourteen percent of 64 cells tested positive for face receptive fields, 32% of 687 cells tested positive for upper-extremity receptive fields, and 21% of 242 cells tested positive for lower-extremity receptive fields. Sixty-eight cells (24%) demonstrated multiple-joint receptive fields. Ninety-three cells (65%) with movement-related receptive fields were located in the dorsal half of the STN, and 96.8% of these were located in the rostral two thirds of the STN. Analysis of receptive field locations from pooled data and along individual electrode tracks failed to reveal a consistent somatotopic organization. CONCLUSIONS: Data from this study demonstrate a regional compartmentalization of neurons with movement-related receptive fields within the STN, supporting the existence of specific motor territories within the STN in patients suffering from PD.     

Cortical connections of the inferior parietal cortical convexity of the macaque monkey

We traced the cortical connections of the 4 cytoarchitectonic fields--Opt, PG, PFG, PF--forming the cortical convexity of the macaque inferior parietal lobule (IPL). Each of these fields displayed markedly distinct sets of connections. Although Opt and PG are both targets of dorsal visual stream and temporal visual areas, PG is also target of somatosensory and auditory areas. Primary parietal and frontal connections of Opt include area PGm and eye-related areas. In contrast, major parietal and frontal connections of PG include IPL, caudal superior parietal lobule (SPL), and agranular frontal arm-related areas. PFG is target of somatosensory areas and also of the medial superior temporal area (MST) and temporal visual areas and is connected with IPL, rostral SPL, and ventral premotor arm- and face-related areas. Finally, PF is primarily connected with somatosensory areas and with parietal and frontal face- and arm-related areas. The present data challenge the bipartite subdivision of the IPL convexity into a caudal and a rostral area (7a and 7b, respectively) and provide a new anatomical frame of reference of the macaque IPL convexity that advances our present knowledge on the functional organization of this cortical sector, giving new insight into its possible role in space perception and motor control.     

Evidence for Visual Cortical Area Homologs in Cat and Macaque Monkey

The maps of visuotopically discrete visual cerebral corticalareas in the cat and the macaque monkey are compared and gapsin knowledge are identified that limit such comparisons. Catareas 17, 18, and 19 can be equated with macaque areas VI, V2,and V3, respectively, based on criteria of relative positionin the cortical mantle, internal organization of visual fieldrepresentations, and trans- and subcortical connections. Usingthese same criteria, a visual area on the medial bank of thelateral suprasylvian sulcus (area PMLS) in the cat can be equatedwith macaque area V5. The equivalences are supported by dataon neuronal receptive field properties and the contributionsthe areas make to visual behavior. Although the data are scantyfor most other visual areas, there are enough data tentativelyto equate collectively cat areas 20a and 20b with macaque areasTF and TH and to liken cat areas 21a and 21b with macaque areaV4. What is not clear is if there is a region in cat that isequivalent to area TE in the macaque monkey. If there is, itlikely lies on the banks of the posterior suprasylvian sulcusbetween areas 20 and 21 and the polysensory cortex of the posteriorectosylvian gyrus. Knowledge gained from prior research on macaqueareas V4 and TE can be used to formulate specific additionalinvestigations of cat area 21 and the uncharted posterior suprasylviansulcus. In addition, prior investigations carried out on catarea 20 can be used to devise specific explorations of macaqueareas TF and TH.     

Structure of the excitatory receptive fields of infragranular forelimb neurons in the rat primary somatosensory cortex responding to touch

We quantitatively studied the excitatory receptive fields of 297 neurons recorded from the forelimb infragranular somatosensory cortex of the rat while touch stimuli were applied to discrete locations on the forelimbs. Receptive fields were highly heterogeneous, but they were regulated, on average, by an underlying spatio-temporal structure. We found the following. (i) Neurons responded with decreasing magnitude and increasing latency when the stimulus was moved from the primary location to secondary locations and to far ispilateral locations of their excitatory receptive fields, displaying smooth transitions from the primary location to secondary locations. (ii) Receptive field patterns revealed functional connectivity between the digits and ventral palm, which did not depend on whether the digits were stimulated dorsally or ventrally. (iii) The structure of the receptive fields (i.e. the neural responses to stimulation of secondary locations compared to the neural responses to stimulation of the primary location), reflected cortical (rather than body) distances. (iv) There was a functional separation between the forepaw and the rest of the forelimb. Namely: if the primary location was in the digits or palm, secondary locations were biased toward the digits and palm; if the primary location was in rest of the forelimb, secondary locations appeared equally distributed over forelimb, digits and palm. (v) More than 40% of neurons extended their receptive field to the ipsilateral forelimb, without any evident spatial organization. Overall, the stimuli evoked approximately 3 times more spikes from secondary responses than from primary responses. These results suggest that a rich repertoire of spatio-temporal responses is available for encoding tactile information. This highly distributed receptive field structure provides the electrophysiological architecture for studying organization and plasticity of cortical somatosensory processing.     

Feature article: the structure and function of dynamic cortical and thalamic receptive fields

Under natural conditions, animals must process spatiotemporally complex signals in order to guide adaptive behavior. It follows that the response properties of neurons should reflect the dynamic nature of such signals. Recently, several studies have demonstrated the existence of time-varying receptive fields in the auditory, visual and somatosensory thalamocortical pathways. The characteristics of these receptive fields suggest that they are constrained by the need to actively interpret time-varying stimuli. Here, we review these studies, the possible functions of these receptive fields, and how they might be generated in the thalamocortical pathway.     

Increased receptive field size in the surround of chronic lesions in the adult cat visual cortex

Visual cortical lesions destroy the target cells for geniculocortical fibers from a certain retinotopic region. This leads to a cortical scotoma. We have investigated the receptive fields of cells in the visual cortex before, 2 days and 2 months after focal ibotenic acid lesions in the adult cat visual cortex and have found signs of receptive field plasticity in the surroundings of the chronic but not the acute and subacute excitotoxic lesions. In the subacute state (first two days post lesion) receptive field sizes of cells at the border of the lesion were reduced in size or remained unchanged. Remapping of cortical receptive fields 2 months later revealed a number of cells with multifold enlarged receptive fields at the border of the lesion. The cells with enlarged receptive fields displayed orientation and direction selectivity like normal cells. The size increase appeared not specifically directed towards the scotoma; however, the enlarged receptive fields can reduce the extent of a cortical scotoma, since previously unresponsive regions of the visual field activate cortical cells at the border of the lesion. This late receptive field plasticity could serve as a mechanism for the filling-in of cortical scotomata observed in patients with visual cortex lesions.     

Spatiotemporal properties of layer V neurons of the rat primary somatosensory cortex.

Animals in their natural environments actively process spatiotemporally complex sensory signals in order to guide adaptive behavior. It therefore seems likely that the properties of both single neurons and neural ensembles should reflect the dynamic nature of such interactions. During exploratory behaviors, rats move their whiskers to actively discriminate between different tactile features. We investigated whether this dynamic sensory processing was reflected in the spatial and temporal properties of neurons in layer V of the 'whisker area' in the rat primary somatosensory cortex. We found that the majority of layer V neurons had large (8.5+/-4.9 whiskers) spatiotemporal receptive fields (i.e. individual cells responded best to different whiskers as a function of post-stimulus time), and that the excitatory responses of surround whiskers formed a spatial gradient of excitation that seemed to reflect the greater use of the ventral and caudal whiskers during natural behaviors. Analyses of ensembles of layer V neurons revealed that single-whisker stimuli activated a portion of layer V that extends well beyond a single cortical column (average of 5.6 barrel cortical columns). Based on these results, we conclude that the rat primary somatosensory cortex does not appear to operate as a static decoder of tactile information. On the contrary, our data suggest that tactile processing in rats is likely to involve the on-going interactions between populations of broadly tuned neurons in the thalamocortical pathway.     

Modulation of responses to optic flow in area 7a by retinotopic and oculomotor cues in monkey

Perception of two- and three-dimensional optic flow critically depends upon extrastriate cortices that are part of the 'dorsal stream' for visual processing. Neurons in area 7a, a sub-region of the posterior parietal cortex, have a dual sensitivity to visual input and to eye position. The sensitivity and selectivity of area 7a neurons to three sensory cues - optic flow, retinotopic stimulus position and eye position - were studied. The visual response to optic flow was modulated by the retinotopic stimulus position and by the eye position in the orbit. The position dependence of the retinal and eye position modulation (i.e. gain field) were quantified by a quadratic regression model that allowed for linear or peaked receptive fields. A local maximum (or minimum) in both the retinotopic fields and the gain fields was observed, suggesting that these sensory qualities are not necessarily linearly represented in area 7a. Neurons were also found that simply encoded the eye position in the absence of optic flow. The spatial tuning for the eye position signals upon stationary stimuli and optic flow was not the same, suggesting multiple anatomical sources of the signals. These neurons can provide a substrate for spatial representation while primates move in the environment.      

Stimulus-dependent modulations of correlated high-frequency oscillations in cat visual cortex

The hypothesis that correlated neural activity is involved in the cortical representation of visual stimuli was examined by recording multi-unit activity and local field potentials from neurons with non- overlapping receptive fields in areas 17 and 18. Using coherence functions, correlations of oscillatory patterns (35-100 Hz) of neural signals were investigated under three stimulus conditions: (i) a whole field grating or a long bar moving across both receptive fields; (ii) masking the region between both receptive fields while stimulating the remaining visual field; and (iii) two separate stimuli simultaneously moving in opposite directions. Coherences of oscillations were found to be significantly higher in the first stimulus condition than in the other two conditions. Since different visual stimuli were reflected in the coherence of neural activity, we concluded that correlated neural activity is a potential candidate for coding of sensory information.      

Form, Function, and Intracortical Projections of Neurons in the Striate Cortex of the Monkey Macacus nemestrinus

Single neurons were recorded in the striate visual cortex (area17) of the old-world monkey Macacus namestrinus. Eight pyramidalneurons, seven spiny stellate neu rons, two basket cells, aclutch cell, and a chandelier cell were filled intracellularywith HRP. Their receptive fields were consistent with previoussingle-unit studies. Their axonal arbors were less elaboratethan in equivalent neurons in the cat, but the laminar specificityof the houtons was very much more precise in the monkey thanin the cat. Nevertheless, the basic cortical circuits in catand monkey appear to hevery similar.     

Role of the mode of sensory stimulation in presurgical brain mapping in which functional magnetic resonance imaging is used

OBJECT: The aim of this study was to evaluate different types of sensory stimulation used to distinguish between microvasculature and venous drainage on functional magnetic resonance (fMR) images with blood oxygen level-dependent (BOLD) contrast. METHODS: Seven volunteers received three sensory stimulations. One consisted of small discontinuous automated pokes to the ventral aspect of the right thumbtip. The other two were delivered by the investigator, who vigorously brushed the ventral aspect of the right thumbtip either alone or in combination with the thenar region. Seven contiguous axial slices of the head were acquired using echoplanar fMR imaging during each mode of stimulation. Boxcar analysis and Student's t-test were performed. Cluster analysis was used to determine significant differences between rest and activation phases. The major findings were 1) that a discontinuous sensory stimulation involving a small skin area was able to evoke a limited activated area in the postcentral gyrus with a low activation index (AI [2%]); 2) that this limited activated area was included in the activated area elicited by the continuous sensory stimulations; and 3) that this also evoked multiple activated areas exhibiting AIs of either approximately 2% or greater than 5%. This indicated that the limited discontinuous tactile stimulation evoked a BOLD-contrast fMR image essentially of microvasculature, whereas the more extensive continuous stimulations evoked a BOLD-contrast fMR image in both microvasculature and venous drainage. CONCLUSIONS: Different sensory stimulations are necessary to differentiate primary sensory cortex from venous drainage for presurgical brain mapping.