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.
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.
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’.
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.
Many of the adaptive changes in the functional organization of parietal cortex of humans emerged ... more Many of the adaptive changes in the functional organization of parietal cortex of humans emerged in past in the early primates as they depended on visually guided forelimb use to grasp branches and food. Currently, human, apes and some monkeys have four well-defined subdivisions of anterior parietal cortex, areas 3a, 3b, 1 and 2 of Brodmann. In some of the smaller monkeys, and in stepsirrine primates (galagos, lemurs, and lorises), especially areas 1 and 2 are less developed, and the existence of an area 2 is questionable. In galagos, area 3b, the homologue of S1 in other mammals, has a more primitive somatotopy, is less devoted to representing the hand, and information from facial whiskers is more important. Humans and other primates also have more somatosensory areas in lateral parietal cortex than most mammals. While the regions of the second somatosensory area, S2 is divided into S2 and the parietal ventral area, PV in most mammals, primates have the additional caudal ad rostral ventral somatosensory areas, VSc and VSr. Posterior parietal cortex is another region of posterior cortex that has changed greatly from non-primate ancestors in having a more caudal half that is heavily devoted to further processing visual information for guiding different actions, such as running, reaching, looking, and grasping. All primates have at least 8 small subdivisions or domains in PPC, and have matching domains in premotor and motor cortex. In humans, domains for speech and tool use appear to have been added, and other parts of PPC have expanded. In addition, parts of PPC are differently specialized in the right and left cerebral hemispheres of humans more than in other primates.
Detailed electrophysiological maps of the representations of trunk and adjacent body parts in are... more Detailed electrophysiological maps of the representations of trunk and adjacent body parts in area 3b and area 1 of somatosensory cortex were obtained in three macaque monkeys (Macaca mulatta and Macaca radiata) of either sex. A total of 211 microelectrode penetrations 250-300 microm apart resulted in 1,190 recording sites. During penetrations deep into the posterior bank of the central sulcus, recordings were made every 300 microm to depths of 6-7 mm until sites unresponsive to somatic stimuli were reached. Cortex was later cut parasagittally and sections were stained for cytochrome oxidase (CO) or Nissl substance. Contrary to expectations from earlier reports, the genitalia were represented lateral to the representations of the foot in cortex along the area 3b/1 border. The gluteal skin including the gluteal pads and the base of the tail were also represented in this section of cortex. Only a small region of cortex was devoted to the genitalia, and neurons in this cortex had receptive fields that were large and typically included skin of the inner thigh and belly. The lower, middle and upper trunk were represented more laterally, followed by the neck, upper head and arm. The receptive fields on the trunk were roughly the same size as those for the middle and lower trunk and slightly smaller on the upper trunk.
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.
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.
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’.
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.
Many of the adaptive changes in the functional organization of parietal cortex of humans emerged ... more Many of the adaptive changes in the functional organization of parietal cortex of humans emerged in past in the early primates as they depended on visually guided forelimb use to grasp branches and food. Currently, human, apes and some monkeys have four well-defined subdivisions of anterior parietal cortex, areas 3a, 3b, 1 and 2 of Brodmann. In some of the smaller monkeys, and in stepsirrine primates (galagos, lemurs, and lorises), especially areas 1 and 2 are less developed, and the existence of an area 2 is questionable. In galagos, area 3b, the homologue of S1 in other mammals, has a more primitive somatotopy, is less devoted to representing the hand, and information from facial whiskers is more important. Humans and other primates also have more somatosensory areas in lateral parietal cortex than most mammals. While the regions of the second somatosensory area, S2 is divided into S2 and the parietal ventral area, PV in most mammals, primates have the additional caudal ad rostral ventral somatosensory areas, VSc and VSr. Posterior parietal cortex is another region of posterior cortex that has changed greatly from non-primate ancestors in having a more caudal half that is heavily devoted to further processing visual information for guiding different actions, such as running, reaching, looking, and grasping. All primates have at least 8 small subdivisions or domains in PPC, and have matching domains in premotor and motor cortex. In humans, domains for speech and tool use appear to have been added, and other parts of PPC have expanded. In addition, parts of PPC are differently specialized in the right and left cerebral hemispheres of humans more than in other primates.
Detailed electrophysiological maps of the representations of trunk and adjacent body parts in are... more Detailed electrophysiological maps of the representations of trunk and adjacent body parts in area 3b and area 1 of somatosensory cortex were obtained in three macaque monkeys (Macaca mulatta and Macaca radiata) of either sex. A total of 211 microelectrode penetrations 250-300 microm apart resulted in 1,190 recording sites. During penetrations deep into the posterior bank of the central sulcus, recordings were made every 300 microm to depths of 6-7 mm until sites unresponsive to somatic stimuli were reached. Cortex was later cut parasagittally and sections were stained for cytochrome oxidase (CO) or Nissl substance. Contrary to expectations from earlier reports, the genitalia were represented lateral to the representations of the foot in cortex along the area 3b/1 border. The gluteal skin including the gluteal pads and the base of the tail were also represented in this section of cortex. Only a small region of cortex was devoted to the genitalia, and neurons in this cortex had receptive fields that were large and typically included skin of the inner thigh and belly. The lower, middle and upper trunk were represented more laterally, followed by the neck, upper head and arm. The receptive fields on the trunk were roughly the same size as those for the middle and lower trunk and slightly smaller on the upper trunk.
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