Jamie L. Reed

Widespread spatial integration in primary somatosensory cortex

Tactile discrimination depends on integration of information from the discrete receptive fields (RFs) of peripheral sensory afferents. Because this information is processed over a hierarchy of subcortical nuclei and cortical areas, the integration likely occurs at multiple levels. The current study presents results indicating that neurons across most of the extent of the hand representation in monkey primary somatosensory cortex (area 3b) interact, even when these neurons have separate RFs. We obtained simultaneous recordings by using a 100-electrode array implanted in the hand representation of primary somatosensory cortex of two anesthetized owl monkeys. During a series of 0.5-s skin indentations with single or dual probes, the distance between electrodes from which neurons with synchronized spike times were recorded exceeded 2 mm. The results provide evidence that stimuli on different parts of the hand influence the degree of synchronous firing among a large population of neurons. Because spike synchrony potentiates the activation of commonly targeted neurons, synchronous neural activity in primary somatosensory cortex can contribute to discrimination of complex tactile stimuli.

The organization of frontoparietal cortex in the tree shrew (Tupaia belangeri): II. Connectional evidence for a frontal-posterior parietal network

Tree shrews are small squirrel‐like mammals that are the closest living relative to primates available for detailed neurobiological study. In a recent study (Remple et al. [2006] J. Comp. Neurol. 497:133–154), we provided anatomical and electrophysiological evidence that the frontoparietal cortex of tree shrews has two motor fields (M1 and M2) and five somatosensory fields (3a, 3b, S2, somatosensory caudal area [SC], and parietal ventral area [PV]). In the present study, we injected anatomical tracers into M1, M2, 3a, 3b, SC, and posterior parietal cortex to establish the ipsilateral cortical connections of these areas. The results provide evidence for a number of new cortical areas including medial motor and somatosensory areas (MMA and MSA), three posterior parietal areas (PPd, PPv, and PPc), and an area ventral to temporal inferior cortex (TIV). M1 receives topographic projections from M2, MMA, 3a, and PPv, and nontopographic connections from the temporal anterior and dorsal areas (TA and TD), PPc, TIV, and MSA. The connections of M2 are similar to those of M1, except that M2 receives denser projections from TIV, PPc, and dorsal frontal cortex and sparser input from M1. Areas 3a, 3b, and SC receive dense topographic projections from each other, S2, and PV and sparser connections from PPd and PPv. Area 3a receives additional input from posterior parietal and temporal regions and from M1 and MMA. Overall, the frontoparietal connections of tree shrew cortex are most similar to those of prosimian primates and quite different from those of more distant relatives such as rats. J. Comp. Neurol. 501:121–149, 2007.

Spatiotemporal Properties of Neuron Response Suppression in Owl Monkey Primary Somatosensory Cortex When Stimuli Are Presented to Both Hands

Despite the lack of ipsilateral receptive fields (RFs) for neurons in the hand representation of area 3b of primary somatosensory cortex, interhemispheric interactions have been reported to varying degrees. We investigated spatiotemporal properties of these interactions to determine the following: response types, timing between stimuli to evoke the strongest bimanual interactions, topographical distribution of effects, and their dependence on similarity of stimulus locations on the two hands. We analyzed response magnitudes and latencies of single neurons and multineuron clusters recorded from 100-electrode arrays implanted in one hemisphere of each of two anesthetized owl monkeys. Skin indentations were delivered to the two hands simultaneously and asynchronously at mirror locations (matched sites on each hand) and nonmirror locations. Since multiple neurons were recorded simultaneously, stimuli on the contralateral hand could be within or outside of the classical RFs of any given neuron. For most neurons, stimulation on the ipsilateral hand suppressed responses to stimuli on the contralateral hand. Maximum suppression occurred when the ipsilateral stimulus was presented 100 ms before the contralateral stimulus onset (p < 0.0005). The longest stimulus onset delay tested (500 ms) allowed contralateral responses to recover to control levels (p = 0.428). Stimulation on mirror digits did not differ from stimulation on nonmirror locations (p = 1.000). These results indicate that interhemispheric interactions are common in area 3b, somewhat topographically diffuse, and maximal when the suppressing ipsilateral stimulus precedes the contralateral stimulus. Our findings point to a neurophysiological basis for “interference” effects found in human psychophysical studies of bimanual stimulation.

Superior colliculus connections with visual thalamus in gray squirrels (Sciurus carolinensis): evidence for four subdivisions within the pulvinar complex.

As diurnal rodents with a well‐developed visual system, squirrels provide a useful comparison of visual system organization with other highly visual mammals such as tree shrews and primates. Here, we describe the projection pattern of gray squirrel superior colliculus (SC) with the large and well‐differentiated pulvinar complex. Our anatomical results support the conclusion that the pulvinar complex of squirrels consists of four distinct nuclei. The caudal (C) nucleus, distinct in cytochrome oxidase (CO), acetylcholinesterase (AChE), and vesicular glutamate transporter‐2 (VGluT2) preparations, received widespread projections from the ipsilateral SC, although a crude retinotopic organization was suggested. The caudal nucleus also received weaker projections from the contralateral SC. The caudal nucleus also projects back to the ipsilateral SC. Lateral (RLl) and medial (RLm) parts of the previously defined rostral lateral pulvinar (RL) were architectonically distinct, and each nucleus received its own retinotopic pattern of focused ipsilateral SC projections. The SC did not project to the rostral medial (RM) nucleus of the pulvinar. SC injections also revealed ipsilateral connections with the dorsal and ventral lateral geniculate nuclei, nuclei of the pretectum, and nucleus of the brachium of the inferior colliculus and bilateral connections with the parabigeminal nuclei. Comparisons with other rodents suggest that a variously named caudal nucleus, which relays visual inputs from the SC to temporal visual cortex, is common to all rodents and possibly most mammals. RM and RL divisions of the pulvinar complex also appear to have homologues in other rodents. J. Comp. Neurol. 519:1071–1094, 2011.

Organization of frontoparietal cortex in the tree shrew (Tupaia belangeri). I. Architecture, microelectrode maps, and corticospinal connections

Despite extensive investigation of the motor cortex of primates, little is known about the organization of motor cortex in tree shrews, one of their closest living relatives. We investigated the organization of frontoparietal cortex in Belangers tree shrews (Tupaia belangeri) by using intracortical microstimulation (ICMS), corticospinal tracing, and detailed histological analysis. The results provide evidence for the subdivision of tree shrew frontoparietal cortex into seven distinct areas (five are newly identified), including two motor fields (M1 and M2) and five somatosensory fields (3a, 3b, S2, PV, and SC). The types of movements evoked in M1 and M2 were similar, but M2 required higher currents to elicit movements and had few connections to the cervical spinal cord and distinctive cyto‐ and immunoarchitecture. The borders between M1 and the anterior somatosensory regions (3a and 3b) were identified primarily from histological analysis, because thresholds were similar between these regions, and differences in corticospinal neuron distribution were subtle. The caudal (SC) and lateral (S2 and PV) somatosensory fields were identified based on differences in architecture and distribution of corticospinal neurons. Myelin‐dense modules were identified in lateral cortex, in the expected location of the oral, forelimb, and hindlimb representations of S2, and possibly PV. Evidence for a complex primate‐like array of motor fields is lacking in tree shrews, but their motor cortex shares a number of basic features with that of primates, which are not found in more distantly related species, such as rats. J. Comp. Neurol. 497:133–154, 2006.

Response Properties of Neurons in Primary Somatosensory Cortex of Owl Monkeys Reflect Widespread Spatiotemporal Integration

Receptive fields of neurons in somatosensory area 3b of monkeys are typically described as restricted to part of a single digit or palm pad. However, such neurons are likely involved in integrating stimulus information from across the hand. To evaluate this possibility, we recorded from area 3b neurons in anesthetized owl monkeys with 100-electrode arrays, stimulating two hand locations with electromechanical probes simultaneously or asynchronously. Response magnitudes and latencies of single- and multiunits varied with stimulus conditions, and multiunit responses were similar to single-unit responses. The mean peak firing rate for single neurons stimulated within the preferred location was estimated to be ∼26 spike/s. Simultaneous stimulation with a second probe outside the preferred location slightly decreased peak firing rates to ∼22 spike/s. When the nonpreferred stimulus preceded the preferred stimulus by 10-500 ms, peak firing rates were suppressed with greatest suppression when the nonpreferred stimulus preceded by 30 ms (∼7 spike/s). The mean latency for single neurons stimulated within the preferred location was ∼23 ms, and latency was little affected by simultaneous paired stimulation. However, when the nonpreferred stimulus preceded the preferred stimulus by 10 ms, latencies shortened to ∼16 ms. Response suppression occurred even when stimuli were separated by long distances (nonadjacent digits) or long times (500 ms onset asynchrony). Facilitation, though rare, occurred most often when the stimulus onsets were within 0-30 ms of each other. These findings quantify spatiotemporal interactions and support the hypothesis that area 3b is involved in widespread stimulus integration.

The reactivation of somatosensory cortex and behavioral recovery after sensory loss in mature primates

In our experiments, we removed a major source of activation of somatosensory cortex in mature monkeys by unilaterally sectioning the sensory afferents in the dorsal columns of the spinal cord at a high cervical level. At this level, the ascending branches of tactile afferents from the hand are cut, while other branches of these afferents remain intact to terminate on neurons in the dorsal horn of the spinal cord. Immediately after such a lesion, the monkeys seem relatively unimpaired in locomotion and often use the forelimb, but further inspection reveals that they prefer to use the unaffected hand in reaching for food. In addition, systematic testing indicates that they make more errors in retrieving pieces of food, and start using visual inspection of the rotated hand to confirm the success of the grasping of the food. Such difficulties are not surprising as a complete dorsal column lesion totally deactivates the contralateral hand representation in primary somatosensory cortex (area 3b). However, hand use rapidly improves over the first post-lesion weeks, and much of the hand representational territory in contralateral area 3b is reactivated by inputs from the hand in roughly a normal somatotopic pattern. Quantitative measures of single neuron response properties reveal that reactivated neurons respond to tactile stimulation on the hand with high firing rates and only slightly longer latencies. We conclude that preserved dorsal column afferents after nearly complete lesions contribute to the reactivation of cortex and the recovery of the behavior, but second-order sensory pathways in the spinal cord may also play an important role. Our microelectrode recordings indicate that these preserved first-order, and second-order pathways are initially weak and largely ineffective in activating cortex, but they are potentiated during the recovery process. Therapies that would promote this potentiation could usefully enhance recovery after spinal cord injury.

Cortical cell and neuron density estimates in one chimpanzee hemisphere.

Significance Chimpanzees are our closest relatives, and understanding the organization of their brains can help us understand our own evolution. Here we present a detailed examination of cell and neuron densities across the chimpanzee cortex. We found similarities to other mammals, including primary sensory areas with high neuron densities and a trend of decreasing neuron densities along the posterior to anterior axis of the cortex. However, we also found a prefrontal region with anomalously high neuron density that disrupts the trend of decreased neuron densities in frontal brain regions. The data reported here allow valuable comparisons among the brains of our close relative and those of humans and other primates. The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm2 of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.

2010 Special Issue: Statistical analysis of large-scale neuronal recording data

Relating stimulus properties to the response properties of individual neurons and neuronal networks is a major goal of sensory research. Many investigators implant electrode arrays in multiple brain areas and record from chronically implanted electrodes over time to answer a variety of questions. Technical challenges related to analyzing large-scale neuronal recording data are not trivial. Several analysis methods traditionally used by neurophysiologists do not account for dependencies in the data that are inherent in multi-electrode recordings. In addition, when neurophysiological data are not best modeled by the normal distribution and when the variables of interest may not be linearly related, extensions of the linear modeling techniques are recommended. A variety of methods exist to analyze correlated data, even when the data are not normally distributed and the relationships are nonlinear. Here we review expansions of the Generalized Linear Model designed to address these data properties. Such methods are used in other research fields, and the application to large-scale neuronal recording data will enable investigators to determine the variable properties that convincingly contribute to the variances in the observed neuronal measures. Standard measures of neuron properties such as response magnitudes can be analyzed using these methods, and measures of neuronal network activity such as spike timing correlations can be analyzed as well. We have done just that in recordings from 100-electrode arrays implanted in the primary somatosensory cortex of owl monkeys. Here we illustrate how one example method, Generalized Estimating Equations analysis, is a useful method to apply to large-scale neuronal recordings.

Modular processing in the hand representation of primate primary somatosensory cortex coexists with widespread activation.

Neurons in the hand representation of primary somatosensory cortex (area 3b) are known to have discretely localized receptive fields; and these neurons form modules that can be visualized histologically as distinct digit and palm representations. Despite these indicators of the importance of local processing in area 3b, widespread interactions between stimuli presented to locations across the hand have been reported. We investigated the relationship of neuron firing rate with distance from the site of maximum activation in cortex by recording from a 100-electrode array with electrodes spaced 400 μm apart, implanted into the area 3b hand representation in anesthetized owl monkeys. For each stimulated location on the hand, the electrode site where neurons had the highest peak firing rate was defined as the peak activation site. The lesser firing rates of neurons at all other electrode sites in the grid were compared with the firing rates of neurons at the peak activation site. On average, peak firing rates of neurons decreased rapidly with distance away from the peak activation site. The effect of distance on the variance of firing rates was highly significant (P < 0.0001). However, individual neurons retained high firing rates for distances over 3 mm. The clear decline in firing rate with distance from the most activated location indicates that local processing is emphasized in area 3b, while the distance of neurons with reduced but maintained firing rates ≤3-4 mm from the site of best activation demonstrated widespread activation in primary somatosensory cortex.