bioRxiv (Cold Spring Harbor Laboratory), Jun 12, 2022
Studies in galago have not provided a comprehensive description of the organization of eye specif... more Studies in galago have not provided a comprehensive description of the organization of eye specific retino-geniculate-cortical projections to the recipient layers in V1. Here we demonstrate the overall patterns of ocular dominance domains in layers III, IV and VI revealed after injecting the transneuronal tracer wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into one eye. We also correlate these patterns with the array of cytochrome oxidase (CO) blobs in tangential sections through the unfolded and flattened cortex. In layer IV, we observed for the first time that eye-specific domains form an interconnected pattern of bands 200-250 um wide arranged such that they do not show orientation bias and do not meet the V1 border at right angles, as is the case in macaques. We also observed distinct patterns of ocular dominance patches in layer III and layer VI. The patches in layer III, likely corresponding to patches of K LGN input described previously, align with layer IV ocular dominance columns (ODCs) of the same eye dominance. Moreover, the layer III patches overlap partially with virtually all CO blobs in both hemispheres, implying that CO blobs receive K LGN input from both eyes. Finally, we found that CO blobs straddle the border between neighboring layer IV ODCs. These results, together with studies showing that a high percentage of cells in CO blobs are monocular, suggest that CO blobs consist of ipsilateral and contralateral subregions that are in register with underlying layer IV ocular dominance columns of the same eye dominance. In macaques and .
Purpose-To monitor the spontaneous recovery of cervical spinal cord injury (SCI) using longitudin... more Purpose-To monitor the spontaneous recovery of cervical spinal cord injury (SCI) using longitudinal multi-parametric MRI methods. Methods-Quantitative MRI imaging including diffusion tensor imaging (DTI), magnetization transfer (MT), and chemical exchange saturation transfer (CEST) was conducted in anesthetized monkeys at 9.4 T. The structural, cellular and molecular features of the spinal cord were examined before and at different time-points after a dorsal column lesion in each monkey. Results-Images with MT contrast enhanced visualization of the grey and white matter boundaries and the lesion, and permitted differentiation of core and rim compartments within an abnormal volume (AV). At early weeks after SCI, both core and rim exhibited low cellular density and low protein content, with high levels of exchanging hydroxyl, amine, and amide protons, as evidenced by increased apparent diffusion coefficient (ADC) value, decreased fractional anisotropy (FA), decreased magnetization transfer ratio (MTR), decreased nuclear Overhauser effect (NOE), and large CEST effects. Over time, while cellular density and fiber density increased, amide, amine, and hydroxyl levels dropped significantly, but at differing rates. Histology confirmed the nature of the AV to be a cyst. Conclusion-Multi-parametric MRI offers a novel method to quantify the spontaneous changes in structure and cellular and molecular compositions of SC during spontaneous recovery from injury.
Unilateral dorsal column lesions (DCL) at the cervical spinal cord deprive the hand regions of so... more Unilateral dorsal column lesions (DCL) at the cervical spinal cord deprive the hand regions of somatosensory cortex of tactile activation. However, considerable cortical reactivation occurs over weeks to months of recovery. While most studies focused on the reactivation of primary somatosensory area 3b, here, for the first time, we address how the higher-order somatosensory cortex reactivates in the same monkeys after DCL that vary across cases in completeness, post-lesion recovery times, and types of treatments. We recorded neural responses to tactile stimulation in areas 3a, 3b, 1, secondary somatosensory cortex (S2), parietal ventral (PV), and occasionally areas 2/5. Our analysis emphasized comparisons of the responsiveness, somatotopy, and receptive field size between areas 3b, 1, and S2/PV across DCL conditions and recovery times. The results indicate that the extents of the reactivation in higher-order somatosensory areas 1 and S2/PV closely reflect the reactivation in primary somatosensory cortex. Responses in higher-order areas S2 and PV can be stronger than those in area 3b, thus suggesting converging or alternative sources of inputs. The results also provide evidence that both primary and higher-order fields are effectively activated after long recovery times as well as after behavioral and electrocutaneous stimulation interventions.
Here, we review recent work on plasticity and recovery after dorsal column spinal cord injury in ... more Here, we review recent work on plasticity and recovery after dorsal column spinal cord injury in nonhuman primates. Plasticity in the adult central nervous system has been established and studied for the past several decades; however, capacities and limits of plasticity are still under investigation. Studies of plasticity include assessing multiple measures before and after injury in animal models. Such studies are particularly important for improving recovery after injury in patients. In summarizing work by our research team and others, we suggest how the findings from plasticity studies in nonhuman primate models may affect therapeutic interventions for conditions involving sensory loss due to spinal cord injury.
Chronic recordings reveal tactile stimuli can suppress spontaneous activity of neurons in somatos... more Chronic recordings reveal tactile stimuli can suppress spontaneous activity of neurons in somatosensory cortex of awake and anesthetized primates.
Proceedings of the National Academy of Sciences of the United States of America, Mar 6, 2023
Neurons in the early stages of processing sensory information suffer transneuronal atrophy when d... more Neurons in the early stages of processing sensory information suffer transneuronal atrophy when deprived of their activating inputs. For over 40 y, members of our laboratory have studied the reorganization of the somatosensory cortex during and after recovering from different types of sensory loss. Here, we took advantage of the preserved histological material from these studies of the cortical effects of sensory loss to evaluate the histological consequences in the cuneate nucleus of the lower brainstem and the adjoining spinal cord. The neurons in the cuneate nucleus are activated by touch on the hand and arm, and relay this activation to the contralateral thalamus, and from the thalamus to the primary somatosensory cortex. Neurons deprived of activating inputs tend to shrink and sometimes die. We considered the effects of differences in species, type and extent of sensory loss, recovery time after injury, and age at the time of injury on the histology of the cuneate nucleus. The results indicate that all injuries that deprived part or all of the cuneate nucleus of sensory activation result in some atrophy of neurons as reflected by a decrease in nucleus size. The extent of the atrophy is greater with greater sensory loss and with longer recovery times. Based on supporting research, atrophy appears to involve a reduction in neuron size and neuropil, with little or no neuron loss. Thus, the potential exists for restoring the hand to cortex pathway with brain–machine interfaces, for bionic prosthetics, or biologically with hand replacement surgery.
We determined the somatotopy of the face and the oral cavity representation in cortical area 3b o... more We determined the somatotopy of the face and the oral cavity representation in cortical area 3b of New World owl monkeys and squirrel monkeys. Area 3b is apparent as a densely myelinated strip in brain sections cut parallel to the surface of flattened cortex. A narrow myelin-light septum that we have termed the "hand-face septum" separates the hand representation from the more lateral face and mouth representation. The face and oral cavity representation is further divided into a series of myelin-dense ovals. We show that three ovals adjacent to the hand representation correspond to the upper face, upper lip, and chin plus lower lip, whereas three or four more rostral ovals successively represent the contralateral teeth, tongue, and the ipsilateral teeth and tongue. Strips of cortex lateral and medial to the area 3b ovals, possibly corresponding to area 1 and area 3a, respectively, have similar somatotopic sequences. Although previous results suggest the existence of great variability within and across primate species, we conclude that the representations of the face and mouth are highly similar across individuals of the same species, and there are extensive overall similarities across these two species of New World monkeys.
Philosophical Transactions of the Royal Society B, Dec 27, 2021
Early mammals were small and nocturnal. Their visual systems had regressed and they had poor visi... more Early mammals were small and nocturnal. Their visual systems had regressed and they had poor vision. After the extinction of the dinosaurs 66 mya, some but not all escaped the ‘nocturnal bottleneck’ by recovering high-acuity vision. By contrast, early primates escaped the bottleneck within the age of dinosaurs by having large forward-facing eyes and acute vision while remaining nocturnal. We propose that these primates differed from other mammals by changing the balance between two sources of visual information to cortex. Thus, cortical processing became less dependent on a relay of information from the superior colliculus (SC) to temporal cortex and more dependent on information distributed from primary visual cortex (V1). In addition, the two major classes of visual information from the retina became highly segregated into magnocellular (M cell) projections from V1 to the primate-specific temporal visual area (MT), and parvocellular-dominated projections to the dorsolateral visual area (DL or V4). The greatly expanded P cell inputs from V1 informed the ventral stream of cortical processing involving temporal and frontal cortex. The M cell pathways from V1 and the SC informed the dorsal stream of cortical processing involving MT, surrounding temporal cortex, and parietal–frontal sensorimotor domains.This article is part of the theme issue ‘Systems neuroscience through the lens of evolutionary theory’.
Damage to the ascending forelimb afferents in the dorsal columns (DC) of the cervical spinal cord... more Damage to the ascending forelimb afferents in the dorsal columns (DC) of the cervical spinal cord in monkeys impairs forelimb use, particularly hand dexterity. Although considerable recovery has been reported, interpretation of the results is complicated by the reproducibility of the lesion and behavioral assessment. Here we examine the effects of a unilateral DC lesion at the C4-C6 spinal cord level in 4 adult squirrel monkeys. Behavioral performance is assessed on a reach-to-grasp task over 5-13 weeks after lesion. Retrograde tracers were injected into the skin of the fingertips to determine the distribution of axon terminals in the cuneate nucleus and estimate the effectiveness of lesion at the conclusion of each case. The size and level of DC lesion was reflected in the proportion of spared afferents, which ranged from 1% to 25% across monkeys. The experiments produced two major findings. First, the extent of deafferentation in the dorsal column is directly related to the degree of reaching and grasping impairments, and to the reactivation profile and somatotopic reorganization in contralateral primary somatosensory cortex. Second, considerable behavioral recovery and cortical reorganization occurred even in the monkey with only 1% of axons spared in the dorsal column. Our findings suggest that cutaneous inputs from the hand and forelimb are critical to the integrity of functions such as grasping and reaching. In addition, axon branches from peripheral afferents that terminate on neurons in the dorsal horn of the spinal cord are likely central to the functional recovery.
Despite the lack of ipsilateral receptive fields (RFs) for neurons in the hand representation of ... more 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 Ͻ 0.0005). The longest stimulus onset delay tested (500 ms) allowed contralateral responses to recover to control levels (p ϭ 0.428). Stimulation on mirror digits did not differ from stimulation on nonmirror locations (p ϭ 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.
Microelectrode mapping methods were used to define the parietal ventral somatosensory area (PV) o... more Microelectrode mapping methods were used to define the parietal ventral somatosensory area (PV) on the upper bank of the lateral sulcus in five marmosets (Callithrix jacchus). In the same animals, neuroanatomical tracers were placed into electrophysiologically identified sites in PV and/or the second somatosensory area (S2). Foci of anterograde and retrograde label were related to electrophysiological maps of cortical areas and cortical and thalamic architecture. The results lead to the following conclusions: (1) Multiunit recordings from cortex on the upper bank of the lateral sulcus demonstrate that PV is somatotopically organized, with the face representation adjoining area 3b and the hindlimb and tail representations away from this border in cortex deep on the upper bank of the lateral sulcus. The forelimb representation is caudal in PV adjacent to the S2 forelimb representation. The body surface representation in PV approximates a mirror image of that in S2; (2) Areas PV and S2 are less myelinated and have less cytochrome oxidase enzyme activity than area 3b; (3) The ventroposterior inferior nucleus (VPI) of the thalamus provides the major somatosensory projections to PV. PV is reciprocally connected with VPI and anterior pulvinar; (4) PV has ipsilateral cortical connections with areas 3a, 3b, 1, and M1 and higher order somatosensory fields, and at least most of these connections are somatotopically matched; and (5) Callosal connections of PV are with S2 and PV of the other cerebral hemisphere. These results further establish PV as one of at least four somatosensory areas of the lateral sulcus of primates. J.
The nodes of a parietal-frontal pathway that mediates grasping in primates are in anterior intrap... more The nodes of a parietal-frontal pathway that mediates grasping in primates are in anterior intraparietal area (AIP) and ventral premotor cortex (PMv). Nevertheless, multiple somatosensory and motor representations of the hand, in parietal and frontal cortex, respectively, suggest that additional pathways remain unrealized. We explored this possibility in macaque monkeys by injecting retrograde tracers into grasp zones identified in primary motor cortex (M1), PMv, and area 2 with long train electrical stimulation. The M1 grasp zone was densely connected with other frontal cortex motor regions. The remainder of the connections originated from somatosensory areas 3a and second somatosensory cortex/parietal ventral area (S2/PV), and from the medial bank and fundus of the intraparietal sulcus (IPS). The PMv grasp zone was also densely connected with frontal cortex motor regions, albeit to a lesser extent than the M1 grasp zone. The remainder of the connections originated from areas S2/PV and aspects of the inferior parietal lobe such as PF, PFG, AIP, and the tip of the IPS. The area 2 grasp zone was densely connected with the hand representations of somatosensory areas 3b, 1, and S2/PV. The remainder of the connections was with areas 3a and 5 and the medial bank and fundus of the IPS. Connections with frontal cortex were relatively weak and concentrated in caudal M1. Thus, the three grasp zones may be nodes of parallel parietal-frontal pathways. Differential points of origin and termination of each pathway suggest varying functional specializations. Direct and indirect connections between those parietal-frontal pathways likely coordinate their respective functions into an accurate grasp.
This chapters defines subdivisions of the somatosensory cortex in mammals, with a focus on the an... more This chapters defines subdivisions of the somatosensory cortex in mammals, with a focus on the anterior parietal cortex, especially in primates. Most mammals have at least five areas of the somatosensory cortex, with the primary somatosensory cortex (S1) being the most architectonically distinct. S1 of many mammals is not uniform in histological appearance, but is instead divided into modules or patches of granular cortex that express high levels of myelin and cytochrome oxidase (CO) while being separated by septal regions that are dysgranular, poorly myelinated, and have little CO. The modules represent distinct parts of the body (digits, whiskers, etc.). Other modules in S1 of monkeys and probably other primates contain neurons that are activated by either slowly or rapidly adapting cutaneous receptors. Anthropoid primates have more areas of the anterior parietal cortex (areas 3a, 3b, 1, and 2), and more subdivisions of the lateral and the posterior parietal cortex than most mammals, although many of these areas are not architectonically distinct and well defined.
In a series of previous studies, we demonstrated that damage to the dorsal column in the cervical... more In a series of previous studies, we demonstrated that damage to the dorsal column in the cervical spinal cord deactivates the contralateral somatosensory hand cortex and impairs hand use in a reach-to-grasp task in squirrel monkeys. Nevertheless, considerable cortical reactivation and behavioral recovery occurs over the following weeks to months after lesion. This timeframe may also be a window for targeted therapies to promote cortical reactivation and functional reorganization, aiding in the recovery process. Here we asked if and how task specific training of an impaired hand would improve behavioral recovery and cortical reorganization in predictable ways, and if recovery related cortical changes would be detectable using noninvasive functional magnetic resonance imaging (fMRI). We further asked if invasive neurophysiological mapping reflected fMRI results. A reach-to-grasp task was used to test impairment and recovery of hand use before and after dorsal column lesions (DC-lesion). The activation and organization of the affected primary somatosensory cortex (area 3b) was evaluated with two types of fMRI – either blood oxygenation level dependent (BOLD) or cerebral blood volume (CBV) with a contrast agent of monocrystalline iron oxide nanocolloid (MION) – before and after DC-lesion. At the end of the behavioral and fMRI studies, microelectrode recordings in the somatosensory areas 3a, 3b and 1 were used to characterize neuronal responses and verify the somatotopy of cortical reactivations. Our results indicate that even after nearly complete DC lesions, monkeys had both considerable post-lesion behavioral recovery, as well as cortical reactivation assessed with fMRI followed by extracellular recordings. Generalized linear regression analyses indicate that lesion extent is correlated with the behavioral outcome, as well as with the difference in the percent signal change from pre-lesion peak activation in fMRI. Monkeys showed behavioral recovery and nearly complete cortical reactivation by 9–12 weeks post-lesion (particularly when the DC-lesion was incomplete). Importantly, the specific training group revealed trends for earlier behavioral recovery and had higher magnitude of fMRI responses to digit stimulation by 5–8 weeks post-lesion. Specific kinematic measures of hand movements in the selected retrieval task predicted recovery time and related to lesion characteristics better than overall task performance success. For measures of cortical reactivation, we found that CBV scans provided stronger signals to vibrotactile digit stimulation as compared to BOLD scans, and thereby may be the preferred non-invasive way to study the cortical reactivation process after sensory deprivations from digits. When the reactivation of cortex for each of the digits was considered, the reactivation by digit 2 stimulation as measured with microelectrode maps and fMRI maps was best correlated with overall behavioral recovery.
bioRxiv (Cold Spring Harbor Laboratory), Jun 12, 2022
Studies in galago have not provided a comprehensive description of the organization of eye specif... more Studies in galago have not provided a comprehensive description of the organization of eye specific retino-geniculate-cortical projections to the recipient layers in V1. Here we demonstrate the overall patterns of ocular dominance domains in layers III, IV and VI revealed after injecting the transneuronal tracer wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into one eye. We also correlate these patterns with the array of cytochrome oxidase (CO) blobs in tangential sections through the unfolded and flattened cortex. In layer IV, we observed for the first time that eye-specific domains form an interconnected pattern of bands 200-250 um wide arranged such that they do not show orientation bias and do not meet the V1 border at right angles, as is the case in macaques. We also observed distinct patterns of ocular dominance patches in layer III and layer VI. The patches in layer III, likely corresponding to patches of K LGN input described previously, align with layer IV ocular dominance columns (ODCs) of the same eye dominance. Moreover, the layer III patches overlap partially with virtually all CO blobs in both hemispheres, implying that CO blobs receive K LGN input from both eyes. Finally, we found that CO blobs straddle the border between neighboring layer IV ODCs. These results, together with studies showing that a high percentage of cells in CO blobs are monocular, suggest that CO blobs consist of ipsilateral and contralateral subregions that are in register with underlying layer IV ocular dominance columns of the same eye dominance. In macaques and .
Purpose-To monitor the spontaneous recovery of cervical spinal cord injury (SCI) using longitudin... more Purpose-To monitor the spontaneous recovery of cervical spinal cord injury (SCI) using longitudinal multi-parametric MRI methods. Methods-Quantitative MRI imaging including diffusion tensor imaging (DTI), magnetization transfer (MT), and chemical exchange saturation transfer (CEST) was conducted in anesthetized monkeys at 9.4 T. The structural, cellular and molecular features of the spinal cord were examined before and at different time-points after a dorsal column lesion in each monkey. Results-Images with MT contrast enhanced visualization of the grey and white matter boundaries and the lesion, and permitted differentiation of core and rim compartments within an abnormal volume (AV). At early weeks after SCI, both core and rim exhibited low cellular density and low protein content, with high levels of exchanging hydroxyl, amine, and amide protons, as evidenced by increased apparent diffusion coefficient (ADC) value, decreased fractional anisotropy (FA), decreased magnetization transfer ratio (MTR), decreased nuclear Overhauser effect (NOE), and large CEST effects. Over time, while cellular density and fiber density increased, amide, amine, and hydroxyl levels dropped significantly, but at differing rates. Histology confirmed the nature of the AV to be a cyst. Conclusion-Multi-parametric MRI offers a novel method to quantify the spontaneous changes in structure and cellular and molecular compositions of SC during spontaneous recovery from injury.
Unilateral dorsal column lesions (DCL) at the cervical spinal cord deprive the hand regions of so... more Unilateral dorsal column lesions (DCL) at the cervical spinal cord deprive the hand regions of somatosensory cortex of tactile activation. However, considerable cortical reactivation occurs over weeks to months of recovery. While most studies focused on the reactivation of primary somatosensory area 3b, here, for the first time, we address how the higher-order somatosensory cortex reactivates in the same monkeys after DCL that vary across cases in completeness, post-lesion recovery times, and types of treatments. We recorded neural responses to tactile stimulation in areas 3a, 3b, 1, secondary somatosensory cortex (S2), parietal ventral (PV), and occasionally areas 2/5. Our analysis emphasized comparisons of the responsiveness, somatotopy, and receptive field size between areas 3b, 1, and S2/PV across DCL conditions and recovery times. The results indicate that the extents of the reactivation in higher-order somatosensory areas 1 and S2/PV closely reflect the reactivation in primary somatosensory cortex. Responses in higher-order areas S2 and PV can be stronger than those in area 3b, thus suggesting converging or alternative sources of inputs. The results also provide evidence that both primary and higher-order fields are effectively activated after long recovery times as well as after behavioral and electrocutaneous stimulation interventions.
Here, we review recent work on plasticity and recovery after dorsal column spinal cord injury in ... more Here, we review recent work on plasticity and recovery after dorsal column spinal cord injury in nonhuman primates. Plasticity in the adult central nervous system has been established and studied for the past several decades; however, capacities and limits of plasticity are still under investigation. Studies of plasticity include assessing multiple measures before and after injury in animal models. Such studies are particularly important for improving recovery after injury in patients. In summarizing work by our research team and others, we suggest how the findings from plasticity studies in nonhuman primate models may affect therapeutic interventions for conditions involving sensory loss due to spinal cord injury.
Chronic recordings reveal tactile stimuli can suppress spontaneous activity of neurons in somatos... more Chronic recordings reveal tactile stimuli can suppress spontaneous activity of neurons in somatosensory cortex of awake and anesthetized primates.
Proceedings of the National Academy of Sciences of the United States of America, Mar 6, 2023
Neurons in the early stages of processing sensory information suffer transneuronal atrophy when d... more Neurons in the early stages of processing sensory information suffer transneuronal atrophy when deprived of their activating inputs. For over 40 y, members of our laboratory have studied the reorganization of the somatosensory cortex during and after recovering from different types of sensory loss. Here, we took advantage of the preserved histological material from these studies of the cortical effects of sensory loss to evaluate the histological consequences in the cuneate nucleus of the lower brainstem and the adjoining spinal cord. The neurons in the cuneate nucleus are activated by touch on the hand and arm, and relay this activation to the contralateral thalamus, and from the thalamus to the primary somatosensory cortex. Neurons deprived of activating inputs tend to shrink and sometimes die. We considered the effects of differences in species, type and extent of sensory loss, recovery time after injury, and age at the time of injury on the histology of the cuneate nucleus. The results indicate that all injuries that deprived part or all of the cuneate nucleus of sensory activation result in some atrophy of neurons as reflected by a decrease in nucleus size. The extent of the atrophy is greater with greater sensory loss and with longer recovery times. Based on supporting research, atrophy appears to involve a reduction in neuron size and neuropil, with little or no neuron loss. Thus, the potential exists for restoring the hand to cortex pathway with brain–machine interfaces, for bionic prosthetics, or biologically with hand replacement surgery.
We determined the somatotopy of the face and the oral cavity representation in cortical area 3b o... more We determined the somatotopy of the face and the oral cavity representation in cortical area 3b of New World owl monkeys and squirrel monkeys. Area 3b is apparent as a densely myelinated strip in brain sections cut parallel to the surface of flattened cortex. A narrow myelin-light septum that we have termed the "hand-face septum" separates the hand representation from the more lateral face and mouth representation. The face and oral cavity representation is further divided into a series of myelin-dense ovals. We show that three ovals adjacent to the hand representation correspond to the upper face, upper lip, and chin plus lower lip, whereas three or four more rostral ovals successively represent the contralateral teeth, tongue, and the ipsilateral teeth and tongue. Strips of cortex lateral and medial to the area 3b ovals, possibly corresponding to area 1 and area 3a, respectively, have similar somatotopic sequences. Although previous results suggest the existence of great variability within and across primate species, we conclude that the representations of the face and mouth are highly similar across individuals of the same species, and there are extensive overall similarities across these two species of New World monkeys.
Philosophical Transactions of the Royal Society B, Dec 27, 2021
Early mammals were small and nocturnal. Their visual systems had regressed and they had poor visi... more Early mammals were small and nocturnal. Their visual systems had regressed and they had poor vision. After the extinction of the dinosaurs 66 mya, some but not all escaped the ‘nocturnal bottleneck’ by recovering high-acuity vision. By contrast, early primates escaped the bottleneck within the age of dinosaurs by having large forward-facing eyes and acute vision while remaining nocturnal. We propose that these primates differed from other mammals by changing the balance between two sources of visual information to cortex. Thus, cortical processing became less dependent on a relay of information from the superior colliculus (SC) to temporal cortex and more dependent on information distributed from primary visual cortex (V1). In addition, the two major classes of visual information from the retina became highly segregated into magnocellular (M cell) projections from V1 to the primate-specific temporal visual area (MT), and parvocellular-dominated projections to the dorsolateral visual area (DL or V4). The greatly expanded P cell inputs from V1 informed the ventral stream of cortical processing involving temporal and frontal cortex. The M cell pathways from V1 and the SC informed the dorsal stream of cortical processing involving MT, surrounding temporal cortex, and parietal–frontal sensorimotor domains.This article is part of the theme issue ‘Systems neuroscience through the lens of evolutionary theory’.
Damage to the ascending forelimb afferents in the dorsal columns (DC) of the cervical spinal cord... more Damage to the ascending forelimb afferents in the dorsal columns (DC) of the cervical spinal cord in monkeys impairs forelimb use, particularly hand dexterity. Although considerable recovery has been reported, interpretation of the results is complicated by the reproducibility of the lesion and behavioral assessment. Here we examine the effects of a unilateral DC lesion at the C4-C6 spinal cord level in 4 adult squirrel monkeys. Behavioral performance is assessed on a reach-to-grasp task over 5-13 weeks after lesion. Retrograde tracers were injected into the skin of the fingertips to determine the distribution of axon terminals in the cuneate nucleus and estimate the effectiveness of lesion at the conclusion of each case. The size and level of DC lesion was reflected in the proportion of spared afferents, which ranged from 1% to 25% across monkeys. The experiments produced two major findings. First, the extent of deafferentation in the dorsal column is directly related to the degree of reaching and grasping impairments, and to the reactivation profile and somatotopic reorganization in contralateral primary somatosensory cortex. Second, considerable behavioral recovery and cortical reorganization occurred even in the monkey with only 1% of axons spared in the dorsal column. Our findings suggest that cutaneous inputs from the hand and forelimb are critical to the integrity of functions such as grasping and reaching. In addition, axon branches from peripheral afferents that terminate on neurons in the dorsal horn of the spinal cord are likely central to the functional recovery.
Despite the lack of ipsilateral receptive fields (RFs) for neurons in the hand representation of ... more 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 Ͻ 0.0005). The longest stimulus onset delay tested (500 ms) allowed contralateral responses to recover to control levels (p ϭ 0.428). Stimulation on mirror digits did not differ from stimulation on nonmirror locations (p ϭ 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.
Microelectrode mapping methods were used to define the parietal ventral somatosensory area (PV) o... more Microelectrode mapping methods were used to define the parietal ventral somatosensory area (PV) on the upper bank of the lateral sulcus in five marmosets (Callithrix jacchus). In the same animals, neuroanatomical tracers were placed into electrophysiologically identified sites in PV and/or the second somatosensory area (S2). Foci of anterograde and retrograde label were related to electrophysiological maps of cortical areas and cortical and thalamic architecture. The results lead to the following conclusions: (1) Multiunit recordings from cortex on the upper bank of the lateral sulcus demonstrate that PV is somatotopically organized, with the face representation adjoining area 3b and the hindlimb and tail representations away from this border in cortex deep on the upper bank of the lateral sulcus. The forelimb representation is caudal in PV adjacent to the S2 forelimb representation. The body surface representation in PV approximates a mirror image of that in S2; (2) Areas PV and S2 are less myelinated and have less cytochrome oxidase enzyme activity than area 3b; (3) The ventroposterior inferior nucleus (VPI) of the thalamus provides the major somatosensory projections to PV. PV is reciprocally connected with VPI and anterior pulvinar; (4) PV has ipsilateral cortical connections with areas 3a, 3b, 1, and M1 and higher order somatosensory fields, and at least most of these connections are somatotopically matched; and (5) Callosal connections of PV are with S2 and PV of the other cerebral hemisphere. These results further establish PV as one of at least four somatosensory areas of the lateral sulcus of primates. J.
The nodes of a parietal-frontal pathway that mediates grasping in primates are in anterior intrap... more The nodes of a parietal-frontal pathway that mediates grasping in primates are in anterior intraparietal area (AIP) and ventral premotor cortex (PMv). Nevertheless, multiple somatosensory and motor representations of the hand, in parietal and frontal cortex, respectively, suggest that additional pathways remain unrealized. We explored this possibility in macaque monkeys by injecting retrograde tracers into grasp zones identified in primary motor cortex (M1), PMv, and area 2 with long train electrical stimulation. The M1 grasp zone was densely connected with other frontal cortex motor regions. The remainder of the connections originated from somatosensory areas 3a and second somatosensory cortex/parietal ventral area (S2/PV), and from the medial bank and fundus of the intraparietal sulcus (IPS). The PMv grasp zone was also densely connected with frontal cortex motor regions, albeit to a lesser extent than the M1 grasp zone. The remainder of the connections originated from areas S2/PV and aspects of the inferior parietal lobe such as PF, PFG, AIP, and the tip of the IPS. The area 2 grasp zone was densely connected with the hand representations of somatosensory areas 3b, 1, and S2/PV. The remainder of the connections was with areas 3a and 5 and the medial bank and fundus of the IPS. Connections with frontal cortex were relatively weak and concentrated in caudal M1. Thus, the three grasp zones may be nodes of parallel parietal-frontal pathways. Differential points of origin and termination of each pathway suggest varying functional specializations. Direct and indirect connections between those parietal-frontal pathways likely coordinate their respective functions into an accurate grasp.
This chapters defines subdivisions of the somatosensory cortex in mammals, with a focus on the an... more This chapters defines subdivisions of the somatosensory cortex in mammals, with a focus on the anterior parietal cortex, especially in primates. Most mammals have at least five areas of the somatosensory cortex, with the primary somatosensory cortex (S1) being the most architectonically distinct. S1 of many mammals is not uniform in histological appearance, but is instead divided into modules or patches of granular cortex that express high levels of myelin and cytochrome oxidase (CO) while being separated by septal regions that are dysgranular, poorly myelinated, and have little CO. The modules represent distinct parts of the body (digits, whiskers, etc.). Other modules in S1 of monkeys and probably other primates contain neurons that are activated by either slowly or rapidly adapting cutaneous receptors. Anthropoid primates have more areas of the anterior parietal cortex (areas 3a, 3b, 1, and 2), and more subdivisions of the lateral and the posterior parietal cortex than most mammals, although many of these areas are not architectonically distinct and well defined.
In a series of previous studies, we demonstrated that damage to the dorsal column in the cervical... more In a series of previous studies, we demonstrated that damage to the dorsal column in the cervical spinal cord deactivates the contralateral somatosensory hand cortex and impairs hand use in a reach-to-grasp task in squirrel monkeys. Nevertheless, considerable cortical reactivation and behavioral recovery occurs over the following weeks to months after lesion. This timeframe may also be a window for targeted therapies to promote cortical reactivation and functional reorganization, aiding in the recovery process. Here we asked if and how task specific training of an impaired hand would improve behavioral recovery and cortical reorganization in predictable ways, and if recovery related cortical changes would be detectable using noninvasive functional magnetic resonance imaging (fMRI). We further asked if invasive neurophysiological mapping reflected fMRI results. A reach-to-grasp task was used to test impairment and recovery of hand use before and after dorsal column lesions (DC-lesion). The activation and organization of the affected primary somatosensory cortex (area 3b) was evaluated with two types of fMRI – either blood oxygenation level dependent (BOLD) or cerebral blood volume (CBV) with a contrast agent of monocrystalline iron oxide nanocolloid (MION) – before and after DC-lesion. At the end of the behavioral and fMRI studies, microelectrode recordings in the somatosensory areas 3a, 3b and 1 were used to characterize neuronal responses and verify the somatotopy of cortical reactivations. Our results indicate that even after nearly complete DC lesions, monkeys had both considerable post-lesion behavioral recovery, as well as cortical reactivation assessed with fMRI followed by extracellular recordings. Generalized linear regression analyses indicate that lesion extent is correlated with the behavioral outcome, as well as with the difference in the percent signal change from pre-lesion peak activation in fMRI. Monkeys showed behavioral recovery and nearly complete cortical reactivation by 9–12 weeks post-lesion (particularly when the DC-lesion was incomplete). Importantly, the specific training group revealed trends for earlier behavioral recovery and had higher magnitude of fMRI responses to digit stimulation by 5–8 weeks post-lesion. Specific kinematic measures of hand movements in the selected retrieval task predicted recovery time and related to lesion characteristics better than overall task performance success. For measures of cortical reactivation, we found that CBV scans provided stronger signals to vibrotactile digit stimulation as compared to BOLD scans, and thereby may be the preferred non-invasive way to study the cortical reactivation process after sensory deprivations from digits. When the reactivation of cortex for each of the digits was considered, the reactivation by digit 2 stimulation as measured with microelectrode maps and fMRI maps was best correlated with overall behavioral recovery.
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Papers by Hui-xin Qi