The anterior intraparietal area (AIP) is a subregion of area 7b in posterior parietal cortex. AIP... more The anterior intraparietal area (AIP) is a subregion of area 7b in posterior parietal cortex. AIP neurons respond to the sight of objects, as well as to the act of grasping them. We used retrograde transneuronal transport of rabies virus to examine subcortical inputs to AIP in the monkey. Virus transport labeled substantial numbers of neurons in the substantia nigra pars reticulata (SNpr), as well as in the dentate nucleus of the cerebellum. The hotspots of labeled neurons in SNpr and in dentate after AIP injections were separate from those created by virus injections into several other parietal or frontal regions. These observations provide the first evidence that a major output nucleus of the basal ganglia, the SNpr, projects to a region of posterior parietal cortex. In addition, our findings provide further support for the concept that posterior parietal cortex is a target of cerebellar output.
What changes in neural architecture account for the emergence and expansion of dexterity in prima... more What changes in neural architecture account for the emergence and expansion of dexterity in primates? Dexterity, or skill in performing motor tasks, depends on the ability to generate highly fractionated patterns of muscle activity. It also involves the spatiotemporal coordination of activity in proximal and distal muscles across multiple joints. Many motor skills require the generation of complex movement sequences that are only acquired and refined through extensive practice. Improvements in dexterity have enabled primates to manufacture and use tools and humans to engage in skilled motor behaviors such as typing, dance, musical performance, and sports. Our analysis leads to the following synthesis: The neural substrate that endows primates with their enhanced motor capabilities is due, in part, to ( a) major organizational changes in the primary motor cortex and ( b) the proliferation of output pathways from other areas of the cerebral cortex, especially from the motor areas on t...
Journal of the International Neuropsychological Society
This paper highlights major developments over the past two to three decades in the neuropsycholog... more This paper highlights major developments over the past two to three decades in the neuropsychology of movement and its disorders. We focus on studies in healthy individuals and patients, which have identified cognitive contributions to movement control and animal work that has delineated the neural circuitry that makes these interactions possible. We cover advances in three major areas: (1) the neuroanatomical aspects of the “motor” system with an emphasis on multiple parallel circuits that include cortical, corticostriate, and corticocerebellar connections; (2) behavioral paradigms that have enabled an appreciation of the cognitive influences on the preparation and execution of movement; and (3) hemispheric differences (exemplified by limb praxis, motor sequencing, and motor learning). Finally, we discuss the clinical implications of this work, and make suggestions for future research in this area. (JINS, 2017, 23, 768–777)
Proceedings of the National Academy of Sciences of the United States of America, Jan 30, 2016
Modern medicine has generally viewed the concept of "psychosomatic" disease with suspic... more Modern medicine has generally viewed the concept of "psychosomatic" disease with suspicion. This view arose partly because no neural networks were known for the mind, conceptually associated with the cerebral cortex, to influence autonomic and endocrine systems that control internal organs. Here, we used transneuronal transport of rabies virus to identify the areas of the primate cerebral cortex that communicate through multisynaptic connections with a major sympathetic effector, the adrenal medulla. We demonstrate that two broad networks in the cerebral cortex have access to the adrenal medulla. The larger network includes all of the cortical motor areas in the frontal lobe and portions of somatosensory cortex. A major component of this network originates from the supplementary motor area and the cingulate motor areas on the medial wall of the hemisphere. These cortical areas are involved in all aspects of skeletomotor control from response selection to motor preparation ...
The properties of whole soleus (SOL) muscles and of individual motor units were studied in cats 3... more The properties of whole soleus (SOL) muscles and of individual motor units were studied in cats 30-50 wk after self-reinnervation by soleus (SOL) motoneurons (SOL----SOL) or cross-reinnervation by flexor digitorum longus (FDL) motoneurons (FDL----SOL). As in the preceding paper (22), intracellular and glycogen-depletion methods were used to examine the physiological and histochemical properties of individual motor units. The results were compared with data from normal SOL motor units (8, 12). Intentionally self-reinnervated SOL muscles (SOL----SOL; n = 6) were normal in size and wet weight, and all of the five SOL----SOL motor units studied had physiological and histochemical characteristics that matched those of normal SOL units. Cross-reinnervation of SOL by FDL alpha-motoneurons (FDL----SOL; n = 7) produced muscles with wet weights and appearance essentially identical to normal SOL. However, whole-muscle twitch contraction times were much shorter (mean 60.4 ms) than those of norm...
1. Synaptic potentials were recorded intracellularly in tibialis anterior (TA) motoneurons follow... more 1. Synaptic potentials were recorded intracellularly in tibialis anterior (TA) motoneurons following stimulation of a descending brain stem pathway, the medial longitudinal fasciculus (MLF), and three segmental inputs, the homonymous and heteronymous group Ia afferents, the group I afferents from the antagonist, and the cutaneous and muscle afferents. Intracellular stimulation of the motoneurons was used to classify them, based on the properties of the innervated muscle units, into types FF, F(int), FR, and S (6, 16). 2. The sum of the monosynaptic EPSP amplitudes resulting from stimulation of homonymous and heteronymous group Ia afferents (summed group Ia EPSP) was inversely related to motoneuron size, as assessed by motoneuron input resistance, and was inversely related to motor-unit tetanic tension. Type-FF, -FR, and -S motoneurons showed significant differences in the mean amplitude of their summed group Ia EPSPs. 3. The amplitudes of disynaptic IPSPs resulting from stimulation ...
The purpose of this study was to determine (i) if decomposition-based quantitative electromyograp... more The purpose of this study was to determine (i) if decomposition-based quantitative electromyography (DQEMG) could detect changes in motor unit potential (MUP) morphology and motor unit (MU) firing pattern statistics associated with muscle fatigue, (ii) if any detected changes are correlated with surface electromyographic (SEMG) signs of fatigue, and (iii) if significant fatigue-dependent changes are repeatable within individuals. Mean MU firing rates and the morphology of MUPs detected using needle and surface electrodes during constant-torque isometric contractions held until exhaustion were investigated in the brachioradialis (BR) muscle in 10 healthy volunteers (mean age = 28.6 yr, SD ± 3.9). Time dependant changes were investigated using an analysis of variance with normalized time as a main effect. Partial correlation coefficients were computed using a repeated measures analysis of covariance to determine if changes in MU firing rates, needle-detected MUPs and surface-detected MUPs (SMUPs) were related to changes in SEMG signal amplitude and frequency parameters. Intraclass correlation coefficients (ICCs) were used to determine the within-subject repeatability of changes in MU firing rates, and MUP and SMUP parameters. Significant decreases in mean MU firing rates were found along with significant increases in various duration and area related parameters in both MUPs and SMUPs across the fatiguing contraction. The SEMG signal demonstrated the expected changes with fatigue: an increase in amplitude and a decrease in frequency content. SEMG amplitude was significantly positively correlated with SMUP peak-to-peak voltage (r = 0.85, p < 0.05), and SMUP area (r = 0.86, p < 0.05). Mean power frequency was significantly negatively correlated with SMUP negative peak duration (r = À0.74, p < 0.05). The significant time-dependent changes were reliably observed (ICCs were 0.94 for MUP peak to peak amplitude, 0.97 for MUP area and 0.95 for MUP area to amplitude ratio, 0.95 for SMUP peak-to-peak voltage, 0.83 for SMUP area, 0.99 for SMUP negative peak amplitude and 0.88 for SMUP negative peak area). The decreases in mean MU firing rates measured along with the increases in amplitude, duration and area parameters of MUPs and SMUPs and their partial correlation with SEMG amplitude during submaximal fatiguing contractions of the BR, suggest that recruitment is a main cause of increased SEMG amplitude parameters with fatigue. We conclude that DQEMG can be effectively and reliably used to detect changes in physiological characteristics of MUs that accompany fatigue.
Autologous nerve grafts were implanted extraspinally between the medulla and the ipsilateral cerv... more Autologous nerve grafts were implanted extraspinally between the medulla and the ipsilateral cervical spinal cord in adult rats. Four to eight months after implantation, electrical stimulation of the grafts evoked EMG activity in a variety of head and neck muscles in 8/10 rats. In 5/10 rats, electrical stimulation of the graft during inspiration potentiated or inhibited EMG activity in each of the diaphragms. After the recordings were completed, the grafts were cut and their ends soaked in horseradish peroxidase (HRP). The average count of HRP-labeled neurons, both in the spinal cord and brain stem, was 969 (252 to 1961). Most labeled neurons were located within +/- 2 mm of the implant sites, with labeling seen in neurons as far as 9 mm away. In the brain stem, 20 different nuclei were labeled. Among them were the reticular formation, raphe complex, cranial nerve nuclei, the subceruleus, ventrolateral pontine tegmentum regions, and contralateral red nucleus. These results in adult rats showed that (i) CNS axons elongating within peripheral nerve grafts were able to conduct action potentials and maintain functional synapses on CNS neurons; (ii) newly growing neurons were situated in close proximity to the nerve graft; and (iii) many different kinds of central neurons, including monoaminergic and descending spinal tract neurons, can elongate their axons into peripheral nerve grafts.
The normal development of the anatomic relationships between the motoneurons of the tibialis ante... more The normal development of the anatomic relationships between the motoneurons of the tibialis anterior (TA) muscle and their innervated muscle fibers was studied in 1-, 6-, and 12-week-old and adult cats. The motoneurons of the anterior branch and the contralateral posterior branch of the TA nerve were retrogradely labeled with horseradish peroxidase. Within the TA motor nucleus, anterior branch motoneurons (63% of total) were located rostrally and posterior branch motoneurons (37% of total) were located more caudally. The distributions of soma diameters of labeled motoneurons were bimodal in all age groups, allowing a presumptive division into gamma (small) and alpha (large) motoneurons. The posterior branch contained 52% of the total gamma motoneurons but only 28% of the total alpha motoneurons. Within the TA muscle, the regions innervated by the anterior and posterior branches were clearly segregated as determined by glycogen depletion. Myofibrillar ATPase staining at pH 4.4 demonstrated that the posterior branch innervated a higher proportion (56%) of types I and IIA fibers than the anterior. Our results support the hypothesis that a topographic relationship exists between the locus of a motoneuron within its motor nucleus and the position of its innervated muscle fibers within the muscle. Since these topographic relationships apply to all age groups studied, the muscle volume innervated by each muscle nerve branch appears to represent a reproducible developmental unit with distinct anatomic, physiologic and possibly functional properties. This unit may be termed a muscle &quot;compartment.&quot;
We examined the topographic organization of corticospinal neurons in the primary motor cortex and... more We examined the topographic organization of corticospinal neurons in the primary motor cortex and in the two premotor areas on the lateral surface of the hemisphere [i.e., the dorsal premotor area (PMd) and the ventral premotor area (PMv)]. In two macaques, we labeled corticospinal neurons that project beyond T7 or S2 by placing crystals of HRP into the dorsolateral funiculus at these segmental levels. In another seven macaques, we labeled corticospinal neurons that project to specific segmental levels of the spinal cord by injecting the fluorescent tracers fast blue and diamidino yellow into the gray matter of the cervical and lumbosacral segments. In one set of experiments (n = 2), we defined the representations of the arm and leg in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other fluorescent tracer into lower lumbosacral segments (L6-S1) of the same animal. In another set of experiments (n = 5), we defined the representations of distal and proximal parts of the forelimb in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other tracer into upper cervical segments (C2-C4) of the same animal. In the primary motor cortex and the PMd, cortical regions that project to lower cervical segments were largely separate from those that project to lower lumbosacral segments. In the PMv, few neurons were labeled after tracer injections into lower cervical segments or lower lumbosacral segments. However, corticospinal neurons were labeled in the PMv after tracer injections into upper cervical segments and after HRP placement in the dorsolateral funiculus at T7. The region of the PMv that projects to upper cervical segments was separate from that which projects below T7. Cortical regions that project to upper and lower cervical segments of the spinal cord overlapped considerably in the primary motor cortex and in the PMd. Despite this overlap, we found that the regions of the primary motor cortex and PMd that project most densely to upper cervical segments were largely separate from those that project most densely to lower cervical segments. Furthermore, we found two separate regions within area 4 that send corticospinal projections primarily to the lower cervical segments. One of these regions was located within the classical &quot;hand&quot; area of the primary motor cortex. The other was located at the medial edge of arm representation in the primary motor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)
Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BM... more Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BMIs), potentially allows for field potentials to be recorded from the surface of the cerebral cortex for long durations without suffering the host-tissue reaction to the extent that it is common with intracortical microelectrodes. Though the stability of signals obtained from chronically implanted ECoG electrodes has begun receiving attention, to date little work has characterized the effects of long-term implantation of ECoG electrodes on underlying cortical tissue. We implanted and recorded from a high-density ECoG electrode grid subdurally over cortical motor areas of a Rhesus macaque for 666 d. Histological analysis revealed minimal damage to the cortex underneath the implant, though the grid itself was encapsulated in collagenous tissue. We observed macrophages and foreign body giant cells at the tissue-array interface, indicative of a stereotypical foreign body response. Despite thi...
We used anterograde transport of wheat germ agglutininhorseradish peroxidase to examine the patte... more We used anterograde transport of wheat germ agglutininhorseradish peroxidase to examine the pattern of spinal termination of efferents from the supplementary motor area (SMA) and the two caudal cingulate motor areas (CMAd and CMAv). Our analysis was limited to cervical segments of the macaque. For comparison, we also examined the pattern of termination of efferents from the primary motor cortex (M1).
Classically, the spinothalamic (ST) system has been viewed as the major pathway for transmitting ... more Classically, the spinothalamic (ST) system has been viewed as the major pathway for transmitting nociceptive and thermoceptive information to the cerebral cortex. There is a long-standing controversy about the cortical targets of this system. We used anterograde transneuronal transport of the H129 strain of herpes simplex virus type 1 in the Cebus monkey to label the cortical areas that receive ST input. We found that the ST system reaches multiple cortical areas located in the contralateral hemisphere. The major targets are granular insular cortex, secondary somatosensory cortex and several cortical areas in the cingulate sulcus. It is noteworthy that comparable cortical regions in humans consistently display activation when subjects are acutely exposed to painful stimuli. We next combined anterograde transneuronal transport of virus with injections of a conventional tracer into the ventral premotor area (PMv). We used the PMv injection to identify the cingulate motor areas on the medial wall of the hemisphere. This combined approach demonstrated that each of the cingulate motor areas receives ST input. Our meta-analysis of imaging studies indicates that the human equivalents of the three cingulate motor areas also correspond to sites of pain-related activation. The cingulate motor areas in the monkey project directly to the primary motor cortex and to the spinal cord. Thus, the substrate exists for the ST system to have an important influence on the cortical control of movement.
We examined the topographic organization of corticospinal neurons in the primary motor cortex and... more We examined the topographic organization of corticospinal neurons in the primary motor cortex and in the two premotor areas on the lateral surface of the hemisphere [i.e., the dorsal premotor area (PMd) and the ventral premotor area (PMv)]. In two macaques, we labeled corticospinal neurons that project beyond T7 or S2 by placing crystals of HRP into the dorsolateral funiculus at these segmental levels. In another seven macaques, we labeled corticospinal neurons that project to specific segmental levels of the spinal cord by injecting the fluorescent tracers fast blue and diamidino yellow into the gray matter of the cervical and lumbosacral segments. In one set of experiments (n = 2), we defined the representations of the arm and leg in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other fluorescent tracer into lower lumbosacral segments (L6-S1) of the same animal. In another set of experiments (n = 5), we defined the representations of distal and proximal parts of the forelimb in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other tracer into upper cervical segments (C2-C4) of the same animal. In the primary motor cortex and the PMd, cortical regions that project to lower cervical segments were largely separate from those that project to lower lumbosacral segments. In the PMv, few neurons were labeled after tracer injections into lower cervical segments or lower lumbosacral segments. However, corticospinal neurons were labeled in the PMv after tracer injections into upper cervical segments and after HRP placement in the dorsolateral funiculus at T7. The region of the PMv that projects to upper cervical segments was separate from that which projects below T7. Cortical regions that project to upper and lower cervical segments of the spinal cord overlapped considerably in the primary motor cortex and in the PMd. Despite this overlap, we found that the regions of the primary motor cortex and PMd that project most densely to upper cervical segments were largely separate from those that project most densely to lower cervical segments. Furthermore, we found two separate regions within area 4 that send corticospinal projections primarily to the lower cervical segments. One of these regions was located within the classical &quot;hand&quot; area of the primary motor cortex. The other was located at the medial edge of arm representation in the primary motor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)
The anterior intraparietal area (AIP) is a subregion of area 7b in posterior parietal cortex. AIP... more The anterior intraparietal area (AIP) is a subregion of area 7b in posterior parietal cortex. AIP neurons respond to the sight of objects, as well as to the act of grasping them. We used retrograde transneuronal transport of rabies virus to examine subcortical inputs to AIP in the monkey. Virus transport labeled substantial numbers of neurons in the substantia nigra pars reticulata (SNpr), as well as in the dentate nucleus of the cerebellum. The hotspots of labeled neurons in SNpr and in dentate after AIP injections were separate from those created by virus injections into several other parietal or frontal regions. These observations provide the first evidence that a major output nucleus of the basal ganglia, the SNpr, projects to a region of posterior parietal cortex. In addition, our findings provide further support for the concept that posterior parietal cortex is a target of cerebellar output.
What changes in neural architecture account for the emergence and expansion of dexterity in prima... more What changes in neural architecture account for the emergence and expansion of dexterity in primates? Dexterity, or skill in performing motor tasks, depends on the ability to generate highly fractionated patterns of muscle activity. It also involves the spatiotemporal coordination of activity in proximal and distal muscles across multiple joints. Many motor skills require the generation of complex movement sequences that are only acquired and refined through extensive practice. Improvements in dexterity have enabled primates to manufacture and use tools and humans to engage in skilled motor behaviors such as typing, dance, musical performance, and sports. Our analysis leads to the following synthesis: The neural substrate that endows primates with their enhanced motor capabilities is due, in part, to ( a) major organizational changes in the primary motor cortex and ( b) the proliferation of output pathways from other areas of the cerebral cortex, especially from the motor areas on t...
Journal of the International Neuropsychological Society
This paper highlights major developments over the past two to three decades in the neuropsycholog... more This paper highlights major developments over the past two to three decades in the neuropsychology of movement and its disorders. We focus on studies in healthy individuals and patients, which have identified cognitive contributions to movement control and animal work that has delineated the neural circuitry that makes these interactions possible. We cover advances in three major areas: (1) the neuroanatomical aspects of the “motor” system with an emphasis on multiple parallel circuits that include cortical, corticostriate, and corticocerebellar connections; (2) behavioral paradigms that have enabled an appreciation of the cognitive influences on the preparation and execution of movement; and (3) hemispheric differences (exemplified by limb praxis, motor sequencing, and motor learning). Finally, we discuss the clinical implications of this work, and make suggestions for future research in this area. (JINS, 2017, 23, 768–777)
Proceedings of the National Academy of Sciences of the United States of America, Jan 30, 2016
Modern medicine has generally viewed the concept of "psychosomatic" disease with suspic... more Modern medicine has generally viewed the concept of "psychosomatic" disease with suspicion. This view arose partly because no neural networks were known for the mind, conceptually associated with the cerebral cortex, to influence autonomic and endocrine systems that control internal organs. Here, we used transneuronal transport of rabies virus to identify the areas of the primate cerebral cortex that communicate through multisynaptic connections with a major sympathetic effector, the adrenal medulla. We demonstrate that two broad networks in the cerebral cortex have access to the adrenal medulla. The larger network includes all of the cortical motor areas in the frontal lobe and portions of somatosensory cortex. A major component of this network originates from the supplementary motor area and the cingulate motor areas on the medial wall of the hemisphere. These cortical areas are involved in all aspects of skeletomotor control from response selection to motor preparation ...
The properties of whole soleus (SOL) muscles and of individual motor units were studied in cats 3... more The properties of whole soleus (SOL) muscles and of individual motor units were studied in cats 30-50 wk after self-reinnervation by soleus (SOL) motoneurons (SOL----SOL) or cross-reinnervation by flexor digitorum longus (FDL) motoneurons (FDL----SOL). As in the preceding paper (22), intracellular and glycogen-depletion methods were used to examine the physiological and histochemical properties of individual motor units. The results were compared with data from normal SOL motor units (8, 12). Intentionally self-reinnervated SOL muscles (SOL----SOL; n = 6) were normal in size and wet weight, and all of the five SOL----SOL motor units studied had physiological and histochemical characteristics that matched those of normal SOL units. Cross-reinnervation of SOL by FDL alpha-motoneurons (FDL----SOL; n = 7) produced muscles with wet weights and appearance essentially identical to normal SOL. However, whole-muscle twitch contraction times were much shorter (mean 60.4 ms) than those of norm...
1. Synaptic potentials were recorded intracellularly in tibialis anterior (TA) motoneurons follow... more 1. Synaptic potentials were recorded intracellularly in tibialis anterior (TA) motoneurons following stimulation of a descending brain stem pathway, the medial longitudinal fasciculus (MLF), and three segmental inputs, the homonymous and heteronymous group Ia afferents, the group I afferents from the antagonist, and the cutaneous and muscle afferents. Intracellular stimulation of the motoneurons was used to classify them, based on the properties of the innervated muscle units, into types FF, F(int), FR, and S (6, 16). 2. The sum of the monosynaptic EPSP amplitudes resulting from stimulation of homonymous and heteronymous group Ia afferents (summed group Ia EPSP) was inversely related to motoneuron size, as assessed by motoneuron input resistance, and was inversely related to motor-unit tetanic tension. Type-FF, -FR, and -S motoneurons showed significant differences in the mean amplitude of their summed group Ia EPSPs. 3. The amplitudes of disynaptic IPSPs resulting from stimulation ...
The purpose of this study was to determine (i) if decomposition-based quantitative electromyograp... more The purpose of this study was to determine (i) if decomposition-based quantitative electromyography (DQEMG) could detect changes in motor unit potential (MUP) morphology and motor unit (MU) firing pattern statistics associated with muscle fatigue, (ii) if any detected changes are correlated with surface electromyographic (SEMG) signs of fatigue, and (iii) if significant fatigue-dependent changes are repeatable within individuals. Mean MU firing rates and the morphology of MUPs detected using needle and surface electrodes during constant-torque isometric contractions held until exhaustion were investigated in the brachioradialis (BR) muscle in 10 healthy volunteers (mean age = 28.6 yr, SD ± 3.9). Time dependant changes were investigated using an analysis of variance with normalized time as a main effect. Partial correlation coefficients were computed using a repeated measures analysis of covariance to determine if changes in MU firing rates, needle-detected MUPs and surface-detected MUPs (SMUPs) were related to changes in SEMG signal amplitude and frequency parameters. Intraclass correlation coefficients (ICCs) were used to determine the within-subject repeatability of changes in MU firing rates, and MUP and SMUP parameters. Significant decreases in mean MU firing rates were found along with significant increases in various duration and area related parameters in both MUPs and SMUPs across the fatiguing contraction. The SEMG signal demonstrated the expected changes with fatigue: an increase in amplitude and a decrease in frequency content. SEMG amplitude was significantly positively correlated with SMUP peak-to-peak voltage (r = 0.85, p < 0.05), and SMUP area (r = 0.86, p < 0.05). Mean power frequency was significantly negatively correlated with SMUP negative peak duration (r = À0.74, p < 0.05). The significant time-dependent changes were reliably observed (ICCs were 0.94 for MUP peak to peak amplitude, 0.97 for MUP area and 0.95 for MUP area to amplitude ratio, 0.95 for SMUP peak-to-peak voltage, 0.83 for SMUP area, 0.99 for SMUP negative peak amplitude and 0.88 for SMUP negative peak area). The decreases in mean MU firing rates measured along with the increases in amplitude, duration and area parameters of MUPs and SMUPs and their partial correlation with SEMG amplitude during submaximal fatiguing contractions of the BR, suggest that recruitment is a main cause of increased SEMG amplitude parameters with fatigue. We conclude that DQEMG can be effectively and reliably used to detect changes in physiological characteristics of MUs that accompany fatigue.
Autologous nerve grafts were implanted extraspinally between the medulla and the ipsilateral cerv... more Autologous nerve grafts were implanted extraspinally between the medulla and the ipsilateral cervical spinal cord in adult rats. Four to eight months after implantation, electrical stimulation of the grafts evoked EMG activity in a variety of head and neck muscles in 8/10 rats. In 5/10 rats, electrical stimulation of the graft during inspiration potentiated or inhibited EMG activity in each of the diaphragms. After the recordings were completed, the grafts were cut and their ends soaked in horseradish peroxidase (HRP). The average count of HRP-labeled neurons, both in the spinal cord and brain stem, was 969 (252 to 1961). Most labeled neurons were located within +/- 2 mm of the implant sites, with labeling seen in neurons as far as 9 mm away. In the brain stem, 20 different nuclei were labeled. Among them were the reticular formation, raphe complex, cranial nerve nuclei, the subceruleus, ventrolateral pontine tegmentum regions, and contralateral red nucleus. These results in adult rats showed that (i) CNS axons elongating within peripheral nerve grafts were able to conduct action potentials and maintain functional synapses on CNS neurons; (ii) newly growing neurons were situated in close proximity to the nerve graft; and (iii) many different kinds of central neurons, including monoaminergic and descending spinal tract neurons, can elongate their axons into peripheral nerve grafts.
The normal development of the anatomic relationships between the motoneurons of the tibialis ante... more The normal development of the anatomic relationships between the motoneurons of the tibialis anterior (TA) muscle and their innervated muscle fibers was studied in 1-, 6-, and 12-week-old and adult cats. The motoneurons of the anterior branch and the contralateral posterior branch of the TA nerve were retrogradely labeled with horseradish peroxidase. Within the TA motor nucleus, anterior branch motoneurons (63% of total) were located rostrally and posterior branch motoneurons (37% of total) were located more caudally. The distributions of soma diameters of labeled motoneurons were bimodal in all age groups, allowing a presumptive division into gamma (small) and alpha (large) motoneurons. The posterior branch contained 52% of the total gamma motoneurons but only 28% of the total alpha motoneurons. Within the TA muscle, the regions innervated by the anterior and posterior branches were clearly segregated as determined by glycogen depletion. Myofibrillar ATPase staining at pH 4.4 demonstrated that the posterior branch innervated a higher proportion (56%) of types I and IIA fibers than the anterior. Our results support the hypothesis that a topographic relationship exists between the locus of a motoneuron within its motor nucleus and the position of its innervated muscle fibers within the muscle. Since these topographic relationships apply to all age groups studied, the muscle volume innervated by each muscle nerve branch appears to represent a reproducible developmental unit with distinct anatomic, physiologic and possibly functional properties. This unit may be termed a muscle &quot;compartment.&quot;
We examined the topographic organization of corticospinal neurons in the primary motor cortex and... more We examined the topographic organization of corticospinal neurons in the primary motor cortex and in the two premotor areas on the lateral surface of the hemisphere [i.e., the dorsal premotor area (PMd) and the ventral premotor area (PMv)]. In two macaques, we labeled corticospinal neurons that project beyond T7 or S2 by placing crystals of HRP into the dorsolateral funiculus at these segmental levels. In another seven macaques, we labeled corticospinal neurons that project to specific segmental levels of the spinal cord by injecting the fluorescent tracers fast blue and diamidino yellow into the gray matter of the cervical and lumbosacral segments. In one set of experiments (n = 2), we defined the representations of the arm and leg in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other fluorescent tracer into lower lumbosacral segments (L6-S1) of the same animal. In another set of experiments (n = 5), we defined the representations of distal and proximal parts of the forelimb in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other tracer into upper cervical segments (C2-C4) of the same animal. In the primary motor cortex and the PMd, cortical regions that project to lower cervical segments were largely separate from those that project to lower lumbosacral segments. In the PMv, few neurons were labeled after tracer injections into lower cervical segments or lower lumbosacral segments. However, corticospinal neurons were labeled in the PMv after tracer injections into upper cervical segments and after HRP placement in the dorsolateral funiculus at T7. The region of the PMv that projects to upper cervical segments was separate from that which projects below T7. Cortical regions that project to upper and lower cervical segments of the spinal cord overlapped considerably in the primary motor cortex and in the PMd. Despite this overlap, we found that the regions of the primary motor cortex and PMd that project most densely to upper cervical segments were largely separate from those that project most densely to lower cervical segments. Furthermore, we found two separate regions within area 4 that send corticospinal projections primarily to the lower cervical segments. One of these regions was located within the classical &quot;hand&quot; area of the primary motor cortex. The other was located at the medial edge of arm representation in the primary motor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)
Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BM... more Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BMIs), potentially allows for field potentials to be recorded from the surface of the cerebral cortex for long durations without suffering the host-tissue reaction to the extent that it is common with intracortical microelectrodes. Though the stability of signals obtained from chronically implanted ECoG electrodes has begun receiving attention, to date little work has characterized the effects of long-term implantation of ECoG electrodes on underlying cortical tissue. We implanted and recorded from a high-density ECoG electrode grid subdurally over cortical motor areas of a Rhesus macaque for 666 d. Histological analysis revealed minimal damage to the cortex underneath the implant, though the grid itself was encapsulated in collagenous tissue. We observed macrophages and foreign body giant cells at the tissue-array interface, indicative of a stereotypical foreign body response. Despite thi...
We used anterograde transport of wheat germ agglutininhorseradish peroxidase to examine the patte... more We used anterograde transport of wheat germ agglutininhorseradish peroxidase to examine the pattern of spinal termination of efferents from the supplementary motor area (SMA) and the two caudal cingulate motor areas (CMAd and CMAv). Our analysis was limited to cervical segments of the macaque. For comparison, we also examined the pattern of termination of efferents from the primary motor cortex (M1).
Classically, the spinothalamic (ST) system has been viewed as the major pathway for transmitting ... more Classically, the spinothalamic (ST) system has been viewed as the major pathway for transmitting nociceptive and thermoceptive information to the cerebral cortex. There is a long-standing controversy about the cortical targets of this system. We used anterograde transneuronal transport of the H129 strain of herpes simplex virus type 1 in the Cebus monkey to label the cortical areas that receive ST input. We found that the ST system reaches multiple cortical areas located in the contralateral hemisphere. The major targets are granular insular cortex, secondary somatosensory cortex and several cortical areas in the cingulate sulcus. It is noteworthy that comparable cortical regions in humans consistently display activation when subjects are acutely exposed to painful stimuli. We next combined anterograde transneuronal transport of virus with injections of a conventional tracer into the ventral premotor area (PMv). We used the PMv injection to identify the cingulate motor areas on the medial wall of the hemisphere. This combined approach demonstrated that each of the cingulate motor areas receives ST input. Our meta-analysis of imaging studies indicates that the human equivalents of the three cingulate motor areas also correspond to sites of pain-related activation. The cingulate motor areas in the monkey project directly to the primary motor cortex and to the spinal cord. Thus, the substrate exists for the ST system to have an important influence on the cortical control of movement.
We examined the topographic organization of corticospinal neurons in the primary motor cortex and... more We examined the topographic organization of corticospinal neurons in the primary motor cortex and in the two premotor areas on the lateral surface of the hemisphere [i.e., the dorsal premotor area (PMd) and the ventral premotor area (PMv)]. In two macaques, we labeled corticospinal neurons that project beyond T7 or S2 by placing crystals of HRP into the dorsolateral funiculus at these segmental levels. In another seven macaques, we labeled corticospinal neurons that project to specific segmental levels of the spinal cord by injecting the fluorescent tracers fast blue and diamidino yellow into the gray matter of the cervical and lumbosacral segments. In one set of experiments (n = 2), we defined the representations of the arm and leg in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other fluorescent tracer into lower lumbosacral segments (L6-S1) of the same animal. In another set of experiments (n = 5), we defined the representations of distal and proximal parts of the forelimb in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other tracer into upper cervical segments (C2-C4) of the same animal. In the primary motor cortex and the PMd, cortical regions that project to lower cervical segments were largely separate from those that project to lower lumbosacral segments. In the PMv, few neurons were labeled after tracer injections into lower cervical segments or lower lumbosacral segments. However, corticospinal neurons were labeled in the PMv after tracer injections into upper cervical segments and after HRP placement in the dorsolateral funiculus at T7. The region of the PMv that projects to upper cervical segments was separate from that which projects below T7. Cortical regions that project to upper and lower cervical segments of the spinal cord overlapped considerably in the primary motor cortex and in the PMd. Despite this overlap, we found that the regions of the primary motor cortex and PMd that project most densely to upper cervical segments were largely separate from those that project most densely to lower cervical segments. Furthermore, we found two separate regions within area 4 that send corticospinal projections primarily to the lower cervical segments. One of these regions was located within the classical &quot;hand&quot; area of the primary motor cortex. The other was located at the medial edge of arm representation in the primary motor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)
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Papers by Richard Dum