Responses from Area 3b of Somatosensory Cortex to Textured Surfaces during Active Touch in Primate

(1) The purpose of this experiment was to characterize the responses of neurons in somatosensory cortex while the hand was actively moved (stroked) across a textured surface. Surfaces consisted of horizontal gratings that varied by spatial period or ridge-groove ratio (roughness). Surfaces were attached to rectangular blocks. TOP and BOTTOM halves of each block could contain surfaces of different roughness. (2) Velocity and force of the stroke were behaviorally constrained within certain limits and continuously measured and recorded during the stroke. (3) Response samples for each neuron were obtained for repeated presentations of each surface. Statistical analyses consisted of analysis of variance and t tests across surfaces on the data of each neuron, and summary statistics on groups of neurons with similar response characteristics. The interaction effects of behavioral variables (velocity and force) were examined and found not to be significant. (4) The sample mainly consisted of rapidly adapting neurons in area 3b of somatosensory area I (SI). Three main response types were found: (a) GRADED cells showed a monotonic increase in firing rate to increasingly rougher surfaces. This effect was seen in one-third of cells studied and is consistent with other reports. These cells seem to code roughness in the magnitude of their response, (b) In some cells, response to a BOTTOM surface depended on the roughness of the preceding TOP surface. This is analogous to contrast in the visual system. These CONTRAST cells are a novel finding in the somatosensory system, (c) Some cells only responded to surfaces that were completely smooth. These “OFF”-response-type cells were seen in proximity to other cells that responded in a reciprocal fashion to surfaces with ridges, but not to smooth surfaces. SMOOTH cells did not respond to punctate or passively applied stimuli, and therefore could not be classified by adaptation of the responses. (5) An increase in firing rate as spatial period (roughness) increases (with a constant ratio of ridge to groove) seems contrary to vibratory models of texture perception. As spatial period increases, temporal frequency decreases, and thus “tuned” cells should show a decreased response rate. Yet GRADED cells showed an increased response. In addition, response varied on surfaces with different groove size, where spatial period, and thus temporal period, was constant. This suggests that in rapidly adapting neurons, at least for these simple surfaces, texture is coded by the magnitude of the firing rates rather than by its temporal fidelity. Reduced response to smoother surfaces does not exclude increased phase locking, however, so that GRADED cells may still be the same cells that respond to vibration.     

Rapid-Rate Paired Associative Stimulation over the Primary Somatosensory Cortex

Rapid-rate paired associative stimulation (rPAS) involves repeat pairing of peripheral nerve stimulation and Transcranial magnetic stimulation (TMS) pulses at a 5 Hz frequency. RPAS over primary motor cortex (M1) operates with spike-timing dependent plasticity such that increases in corticospinal excitability occur when the nerve and TMS pulse temporally coincide in cortex. The present study investigates the effects of rPAS over primary somatosensory cortex (SI) which has not been performed to date. In a series of experiments, rPAS was delivered over SI and M1 at varying timing intervals between the nerve and TMS pulse based on the latency of the N20 somatosensory evoked potential (SEP) component within each participant (intervals for SI-rPAS: N20, N20-2.5 ms, N20 + 2.5 ms, intervals for M1-rPAS: N20, N20+5 ms). Changes in SI physiology were measured via SEPs (N20, P25, N20-P25) and SEP paired-pulse inhibition, and changes in M1 physiology were measured with motor evoked potentials and short-latency afferent inhibition. Measures were obtained before rPAS and at 5, 25 and 45 minutes following stimulation. Results indicate that paired-pulse inhibition and short-latency afferent inhibition were reduced only when the SI-rPAS nerve-TMS timing interval was set to N20-2.5 ms. SI-rPAS over SI also led to remote effects on motor physiology over a wider range of nerve-TMS intervals (N20-2.5 ms – N20+2.5 ms) during which motor evoked potentials were increased. M1-rPAS increased motor evoked potentials and reduced short-latency afferent inhibition as previously reported. These data provide evidence that, similar to M1, rPAS over SI is spike-timing dependent and is capable of exerting changes in SI and M1 physiology.     

The Effects of Localized Inactivation of Somatosensory Cortex,Area 2, on the Cat Motor Cortex

Direct corticocortical afferents to the primary motor cortex (MI) originate in area 2 and area 3a of the primary somatosensory cortex (SI). The functional and morphological characteristics of the two pathways indicate that they relay different sensory signals to MI. The role of area 2 in relaying peripheral information to the cat MI was studied using electrophysiological techniques. Neurons that responded to stimulation of peripheral receptive fields on the contralateral forepaw were identified in MI by extracellular recordings. In area 2 of SI, neurons with the same receptive field modality and location as those in MI were also identified. Field potentials to electrical stimulation of the peripheral receptive field were recorded at the somatotopically matched sites in both MI and SI. Neuronal activity at the recording site in area 2 was blocked by injection of lidocaine, a local anesthetic. Changes in MI and area 2 responses were monitored before and after inactivation of area 2. Neuronal activity near the injection site was abolished, and evoked potentials (EPs) in area 2 were considerably diminished immediately following the injection. In MI, spontaneous activity levels were altered at some sites, but overall these changes were not significant. MI EPs recorded in response to peripheral stimulation were altered, and various patterns of change were noted in the early and late phases of the EPs. Changes often occurred in only one phase of the response. In some EPs, both early and late phases changed, but the direction and magnitude of change in one phase were not always linked to such changes in the other phase. Both increases and decreases in the amplitude and the area of each phase were observed. The morphological characteristics of the projection were reviewed and related to the findings in the study. It is proposed that inherent features of the pathway may account for the variable patterns of change that were observed.     

Temporal Sharpening of Sensory Responses by Layer V in the Mouse Primary Somatosensory Cortex

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成年大鼠体感皮层局限损伤引起的代表区重组

本文目的是探讨在成年大鼠初级体感皮层（ＳＩ）内进行局限损毁能否引起损毁区周围的代表区重组。在氯胺酮麻醉下用微电极技术测定隐神经代表区（ＳＡＲ）和坐骨神经代表区（ＳＣＲ）,然后用铂电极对ＳＡＲ进行选择性电解损毁。三至四周后进行重复测定。结果表明,在１４例所观察的大鼠中,９例在原损毁区以外发现新生的ＳＡＲ,其面积为０．２０±０．０８ｍｍ２。这表明成年大鼠ＳＩ神经元在中枢损伤后具有一定的重组能力。     

Evidence for Synchronous Activation of Neurons Located in Different Layers of Primary Somatosensory Cortex

Although many studies have examined the columnar organization of primary somatosensory (SI) cortex, the functional relationship among neurons in different layers remains unclear. To understand how activity is coordinated among different cortical layers, the present investigation tested the hypothesis that the initial part of a peripheral stimulus produces a serial pattern of laminar activation in SI cortex. Extracellular discharges of 334 histologically recovered neurons were recorded from the medial bank of the coronal sulcus in nine anesthetized cats during electrical or cutaneous stimulation of the distal forelimb. Mean responses during the initial 50-msec period following stimulus onset were largest in layers IIIb or IV for both types of stimulation, but laminar differences in the magnitude of onset responses were not statistically significant. Among 175 neurons with responses exceeding 0.5 spikes per stimulus, electrical Stimulation consistently produced shorter response latencies than mechanical indentation in the extragranular (II, IIIa, V, VI), but not in the middle (IIIb, IV), cortical layers. The average minimum latencies for different cortical layers ranged from 7.4 to 10.1 msec for responses to electrical stimulation and from 10.3 to 11.6 msec for responses to mechanical indentations, but these laminar differences were not statistically significant. In some experiments, neurons in different layers of a cortical column were recorded simultaneously with dual-electrode assemblies; among 37 neuron pairs in which both neurons responded with more than 0.5 spikes per stimulus, response latencies were similar, even though the neurons were separated by several hundred microns. Cross-correlation analysis of the onset responses for neurons recorded simultaneously from different layers also indicated that many cells throughout a cortical column were activated nearly simultaneously by the initial phase of a peripheral stimulus. Results from the present study are compared with previous reports examining laminar patterns of activation.     

Responsiveness of Reorganized Primary Somatosensory (SI) Cortex after Local Inactivation of Normal SI Cortex in Chronic Spinal Cats

The cortical map of adult cats that sustained spinal cord transection at T₁₂ when they were 2 weeks old is characterized by a clear duplication of the representation of the forelimb, rostral trunk, and neck. The novel representation is located in the cortical region that is, in nonoperated animals, normally devoted to the hindlimb representation. We have investigated the possibility that the reactivation of the deprived hindlimb cortex may be mediated by corticocortical projections from normal to reorganized cortex. The primary somatosensory (SI) cortex was initially mapped to determine the boundaries of the normal and reorganized cortical representations. Somatotopically corresponding regions in both normal and reorganized cortex representing the trunk, the web space, or the shoulder were more precisely mapped. Inactivation of normal cortex was achieved by the nanoinjection of a solution of lidocaine hydrochloride stained with Chicago sky blue. Two major findings are described. First, inactivation of a circumscribed region of normal cortex representing a given receptive field (RF) failed to reduce or inhibit the responsiveness of a somatotopically corresponding RF represented in reorganized cortex. Therefore, it is unlikely that intracortical connections between normal and reorganized cortex could account for the reorganizational processes observed in cats that sustained spinal cord transection at 2 weeks of age. Second, the chemical blockade of normal cortex provoked an increase of the responsiveness and of the size of the peripheral RFs represented in reorganized cortex. This finding suggests that there are corticocortical connections (possibly topographically organized) between normal and reorganized cortex, and that these connections are inhibitory.     

The Arbors of Axons Terminating in Middle Cortical Layers of Somatosensory Area 3b in Owl Monkeys

The arbors of single axons terminating predominantly in layer IV of the representation of the hand in area 3b of owl monkeys were reconstructed from serial brain sections after axons beneath the cortex were severed and horseradish peroxidase was injected into the white matter. In addition to dense terminations in layer IV, these labeled axons generally had branches extending into deeper layer III, and a few had very sparse terminations in layer VI. Terminal arbors ranged from 100 to 900 μm in diameter, and fine branches with synaptic boutons were unevenly distributed, typically grouped in a large central cluster and one or more smaller side clusters. The results are consistent with three broad conclusions: (1) Since the arbors are large relative to the details of the somatotopic map in area 3b, all regions within a single arbor may not be equally effective in activating cortical cells. (2) Spatially separate branches of single axons may relate to spatially separate modules of neurons of the same class in a manner that allows them to receive the same inputs. (3) Many of the somatotopic changes that have been reported in the hand representation as a result of nerve manipulations in adults could result from alterations in synaptic effectiveness within the arbors of single axons.     

Responses in Primary Somatosensory Cortex of Rhesus Monkey to Controlled Application of Embossed Grating and Bar Patterns

Responses of 66 neurons in primary somatosensory cortex (SI) of three anesthetized monkeys (Macaca mulatto) were characterized with grating patterns of 550- to 2900-mm groove width (Gw) and 250-mm ridge width, and/or pairs of 3-mm-wide ridges (bars) spaced 1-20 mm apart. Surfaces were stroked across single fingertips at parametrically varied levels of force ('25-150 g) and velocity ('25-100 mm/sec). The average firing rates (AFRs) of many cells varied with Gw, but force and velocity altered response functions (e.g., from linear to plateau or inverted). Slowly adapting (SA) cells were more sensitive to force, rapidly adapting (RA) cells to velocity. Force and velocity affected all cells sensitive to Gw, which suggests that response independence (e.g., AFR correlated with Gw but not force or velocity) may require active touch

Discharge intervals of many cells replicated stimulus temporal period. This temporal fidelity in SAs far exceeded examples reported for active touch. However, discharge burst duration and AFR increased with Gw, supporting a neural rate rather than temporal code for roughness. Force and velocity altered the Gw at which some cells fired once in phase to stimulus cycle (“tuning point”). Responses to bar edges suggest cortical replication of peripheral mechanoreceptor sensitivity to skin curvature, leading to this temporal fidelity in some cortical cells. Graded RA responses to Gw without obvious stimulus temporal replication may reflect early stages of integrative processing in supra- and infragranular layers that blur obvious temporal patterning and lead to a rate code correlated with spatial variation and proportional to perceived roughness     

Shape Invariant Coding of Motion Direction in Somatosensory Cortex

Invariant representations of stimulus features are thought to play an important role in producing stable percepts of objects. In the present study, we assess the invariance of neural representations of tactile motion direction with respect to other stimulus properties. To this end, we record the responses evoked in individual neurons in somatosensory cortex of primates, including areas 3b, 1, and 2, by three types of motion stimuli, namely scanned bars and dot patterns, and random dot displays, presented to the fingertips of macaque monkeys. We identify a population of neurons in area 1 that is highly sensitive to the direction of stimulus motion and whose motion signals are invariant across stimulus types and conditions. The motion signals conveyed by individual neurons in area 1 can account for the ability of human observers to discriminate the direction of motion of these stimuli, as measured in paired psychophysical experiments. We conclude that area 1 contains a robust representation of motion and discuss similarities in the neural mechanisms of visual and tactile motion processing.     

Reorganization of the Intact Somatosensory Cortex Immediately after Spinal Cord Injury

Sensory deafferentation produces extensive reorganization of the corresponding deafferented cortex. Little is known, however, about the role of the adjacent intact cortex in this reorganization. Here we show that a complete thoracic transection of the spinal cord immediately increases the responses of the intact forepaw cortex to forepaw stimuli (above the level of the lesion) in anesthetized rats. These increased forepaw responses were independent of the global changes in cortical state induced by the spinal cord transection described in our previous work (Aguilar et al., J Neurosci 2010), as the responses increased both when the cortex was in a silent state (down-state) or in an active state (up-state). The increased responses in the intact forepaw cortex correlated with increased responses in the deafferented hindpaw cortex, suggesting that they could represent different points of view of the same immediate state-independent functional reorganization of the primary somatosensory cortex after spinal cord injury. Collectively, the results of the present study and of our previous study suggest that both state-dependent and state-independent mechanisms can jointly contribute to cortical reorganization immediately after spinal cord injury.     

RTTN Mutations Link Primary Cilia Function to Organization of the Human Cerebral Cortex

Polymicrogyria is a malformation of the developing cerebral cortex caused by abnormal organization and characterized by many small gyri and fusion of the outer molecular layer. We have identified autosomal-recessive mutations in RTTN, encoding Rotatin, in individuals with bilateral diffuse polymicrogyria from two separate families. Rotatin determines early embryonic axial rotation, as well as anteroposterior and dorsoventral patterning in the mouse. Human Rotatin has recently been identified as a centrosome-associated protein. The Drosophila melanogaster homolog of Rotatin, Ana3, is needed for structural integrity of centrioles and basal bodies and maintenance of sensory neurons. We show that Rotatin colocalizes with the basal bodies at the primary cilium. Cultured fibroblasts from affected individuals have structural abnormalities of the cilia and exhibit downregulation of BMP4, WNT5A, and WNT2B, which are key regulators of cortical patterning and are expressed at the cortical hem, the cortex-organizing center that gives rise to Cajal-Retzius (CR) neurons. Interestingly, we have shown that in mouse embryos, Rotatin colocalizes with CR neurons at the subpial marginal zone. Knockdown experiments in human fibroblasts and neural stem cells confirm a role for RTTN in cilia structure and function. RTTN mutations therefore link aberrant ciliary function to abnormal development and organization of the cortex in human individuals.     

Axonal Dynamics of Excitatory and Inhibitory Neurons in Somatosensory Cortex

Cortical topography can be remapped as a consequence of sensory deprivation, suggesting that cortical circuits are continually modified by experience. To see the effect of altered sensory experience on specific components of cortical circuits, we imaged neurons, labeled with a genetically modified adeno-associated virus, in the intact mouse somatosensory cortex before and after whisker plucking. Following whisker plucking we observed massive and rapid reorganization of the axons of both excitatory and inhibitory neurons, accompanied by a transient increase in bouton density. For horizontally projecting axons of excitatory neurons there was a net increase in axonal projections from the non-deprived whisker barrel columns into the deprived barrel columns. The axon collaterals of inhibitory neurons located in the deprived whisker barrel columns retracted in the vicinity of their somata and sprouted long-range projections beyond their normal reach towards the non-deprived whisker barrel columns. These results suggest that alterations in the balance of excitation and inhibition in deprived and non-deprived barrel columns underlie the topographic remapping associated with sensory deprivation.     

Tactile-Vibration-Activated Foci in Insular and Parietal-Opercular Cortex Studied with Positron Emission Tomography: Mapping the Second Somatosensory Area in Humans

Positron emission tomographic measurements were used to study the distribution of focal changes in cerebral blood flow (CBF) induced by vibrotactile stimulation of the hands and feet in 22 normal humans. Subjects received bolus intravenous saline injections containing ～ 60 mCi ¹⁵O-labeled water. Active regions during stimulation were defined relative to resting, nonstimulated states. Scan data from different subjects were averaged after stereotactic standardization. The results identified previously described foci of increased CBF in postrolandic sensory cortex (primary somatosensory cortex) and supplementary motor cortex. New statistical testing procedures provided independent demonstrations of two additional increases in regional CBF, bilaterally, within the sylvian fissure. One site along the parietal operculum corresponded to previous conjectures about a second somatosensory cortical area (SII) in humans. Another site also was found on the insula. No topographic organization was found in either location. The discussion considers these responsive areas to innocuous tactile stimuli in reference to suggestions about a role for SII in the perception of pain.