Hui-Xin Qi

Cortical and subcortical plasticity in the brains of humans, primates, and rats after damage to sensory afferents in the dorsal columns of the spinal cord.

The failure of injured axons to regenerate following spinal cord injury deprives brain neurons of their normal sources of activation. These injuries also result in the reorganization of affected areas of the central nervous system that is thought to drive both the ensuing recovery of function and the formation of maladaptive neuronal circuitry. Better understanding of the physiological consequences of novel synaptic connections produced by injury and the mechanisms that control their formation are important to the development of new successful strategies for the treatment of patients with spinal cord injuries. Here we discuss the anatomical, physiological and behavioral changes that take place in response to injury-induced plasticity after damage to the dorsal column pathway in rats and monkeys. Complete section of the dorsal columns of the spinal cord at a high cervical level in monkeys and rats interrupts the ascending axon branches of low threshold mechanoreceptor afferents subserving the forelimb and the rest of the lower body. Such lesions render the corresponding part of the somatotopic representation of primary somatosensory cortex totally unresponsive to tactile stimuli. There are also behavioral consequences of the sensory loss, including an impaired use of the hand/forelimb in manipulating small objects. In monkeys, if some of the afferents from the hand remain intact after dorsal column lesions, these remaining afferents extensively reactivate portions of somatosensory cortex formerly representing the hand. This functional reorganization develops over a postoperative period of 1 month, during which hand use rapidly improves. These recoveries appear to be mediated, at least in part, by the sprouting of preserved afferents within the cuneate nucleus of the dorsal column-trigeminal complex. In rats, such functional collateral sprouting has been promoted by the post-lesion digestion of the perineuronal net in the cuneate nucleus. Thus, this and other therapeutic strategies have the potential of enhancing sensorimotor recoveries after spinal cord injuries in humans.

Anatomic correlates of the face and oral cavity representations in the somatosensory cortical area 3b of monkeys.

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. J. Comp. Neurol. 429:455–468, 2001.

Do superior colliculus projection zones in the inferior pulvinar project to MT in primates

In order to determine the relationship of superior colliculus inputs to thalamic neurons projecting to the middle temporal visual area (MT), injections of wheat germ agglutinin conjugated with horseradish peroxidase were placed in the superior colliculus of three owl monkeys, with injections of Fast Blue in the MT. The locations of labelled terminals and neurons in the posterior thalamus were related to four architectonically distinct nuclei of the inferior pulvinar (Stepniewska & Kaas, Vis. Neurosci.14, pp.1043–1060, 1997). Fast Blue injections in the MT labelled neurons largely in the medial nucleus of the inferior pulvinar. A few labelled neurons were found in the adjoining central medial nucleus of the inferior pulvinar, as well as in the lateral pulvinar and the dorsal lateral geniculate nucleus. Superior colliculus inputs were most dense in the posterior and medial nuclei of the inferior pulvinar. There were sparser inputs to the central lateral nucleus of the inferior pulvinar, locations in the lateral and medial pulvinar, and the dorsal lateral geniculate nucleus. The results indicate that the medial nucleus of the inferior pulvinar, the major projection zone to the MT, does not receive a significant input from the superior colliculus.

Cortical and thalamic connections of the parietal ventral somatosensory area in marmoset monkeys (Callithrix jacchus)

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. Comp. Neurol. 443:168–182, 2002.

Large-Scale Reorganization in the Somatosensory Cortex and Thalamus after Sensory Loss in Macaque Monkeys

Adult brains undergo large-scale plastic changes after peripheral and central injuries. Although it has been shown that both the cortical and thalamic representations can reorganize, uncertainties exist regarding the extent, nature, and time course of changes at each level. We have determined how cortical representations in the somatosensory area 3b and the ventroposterior (VP) nucleus of thalamus are affected by long standing unilateral dorsal column lesions at cervical levels in macaque monkeys. In monkeys with recovery periods of 22–23 months, the intact face inputs expanded into the deafferented hand region of area 3b after complete or partial lesions of the dorsal columns. The expansion of the face region could extend all the way medially into the leg and foot representations. In the same monkeys, similar expansions of the face representation take place in the VP nucleus of the thalamus, indicating that both these processing levels undergo similar reorganizations. The receptive fields of the expanded representations were similar in somatosensory cortex and thalamus. In two monkeys, we determined the extent of the brain reorganization immediately after dorsal column lesions. In these monkeys, the deafferented regions of area 3b and the VP nucleus became unresponsive to the peripheral touch immediately after the lesion. No reorganization was seen in the cortex or the VP nucleus. A comparison of the extents of deafferentation across the monkeys shows that even if the dorsal column lesion is partial, preserving most of the hand representation, it is sufficient to induce an expansion of the face representation.

Anatomical and functional organization of somatosensory areas of the lateral fissure of the New World titi monkey (Callicebus moloch)

The organization of anterior and lateral somatosensory cortex was investigated in titi monkeys (Callicebus moloch). Multiunit microelectrode recordings were used to identify multiple representations of the body, and anatomical tracer injections were used to reveal connections. (1) Representations of the face were identified in areas 3a, 3b, 1, S2, and the parietal ventral area (PV). In area 3b, the face was represented from chin/lower lip to upper lip and neck/upper face in a rostrocaudal sequence. The representation of the face in area 1 mirrored that of area 3b. Another face representation was located in area 3a. Adjoining face representations in S2 and PV exhibited mirror‐image patterns to those of areas 3b and 1. (2) Two representations of the body, the rostral and caudal ventral somatosensory areas (VSr and VSc), were found in the dorsal part of the insula. VSc was roughly a reversal image of the S2 body representation, and VSr was roughly a reversal of PV. (3) Neurons in the insula next to VSr and VSc responded to auditory stimuli or to both auditory and somatosensory stimuli. (4) Injections of tracers within the hand representations in areas 3b, 1, and S2 revealed reciprocal connections between these three areas. Injections in areas 3b and 1 labeled the ventroposterior nucleus, whereas injections in S2 labeled the inferior ventroposterior nucleus. The present study demonstrates features of somatosensory cortex of other monkeys in titi monkeys, while revealing additional features that likely apply to other primates. J. Comp. Neurol. 476:363–387, 2004.

Pallidal and cerebellar afferents to pre‐supplementary motor area thalamocortical neurons in the owl monkey: A multiple labeling study

In the present study, we determined where thalamic neurons projecting to the pre‐supplementary motor area (pre‐SMA) are located relative to pallidothalamic and cerebellothalamic inputs and nuclear boundaries. We employed a triple‐labeling technique in the same owl monkey (Aotus trivirgatus). The cerebellothalamic projections were labeled with injections of wheat germ agglutinin conjugated to horseradish peroxidase, and the pallidothalamic projections were labeled with biotinylated dextran amine. The pre‐SMA was identified by location and movement patterns evoked by intracortical microstimulation and injected with the retrograde tracer cholera toxin subunit B. Brain sections were processed sequentially using different chromogens to visualize all three tracers in the same section. Alternate sections were processed for Nissl cytoarchitecture or acetylcholinesterase chemoarchitecture for nuclear boundaries. The cerebellar nuclei primarily projected to posterior (VLp), medial (VLx), and dorsal (VLd) divisions of the ventral lateral nucleus; the pallidum largely projected to the anterior division (VLa) of the ventral lateral nucleus and the parvocellular part of the ventral anterior nucleus (VApc). However, we also found zones of overlapping projections, as well as interdigitating foci of pallidal and cerebellar label, particularly in border regions of the VLa and VApc. Thalamic neurons labeled by pre‐SMA injections occupied a wide band and were especially concentrated in the VLx and VApc, cerebellar and pallidal territories, respectively. Labeled thalamocortical neurons overlapped cerebellar inputs in the VLd and VApc and overlapped pallidal inputs in the VLa and the ventral medial nucleus. The results demonstrate that inputs from both the cerebellum and globus pallidus are relayed to the pre‐SMA. J. Comp. Neurol. 417:164–180, 2000. ©2000 Wiley‐Liss, Inc.

Projections of the superior colliculus to subdivisions of the inferior pulvinar in New World and Old World monkeys

Patterns of terminals labeled after WGA-HRP injections in the superior colliculus (SC) in squirrel monkeys and macaque monkeys, and after DiI application in marmosets, were related to the architecture of the pulvinar and dorsal lateral geniculate nucleus (LGN). In all studied species, the SC projects densely to two architectonic subdivisions of the inferior pulvinar, the posterior inferior pulvinar nucleus (PIp) and central medial inferior pulvinar nucleus (PIcM). These projection zones expressed substance P. Thus, sections processed for substance P reveal SC termination zones in the inferior pulvinar. The medial subdivision of the inferior pulvinar, PIm, which is known to project to visual area MT, does not receive a significant collicular input. Injections in MT of a squirrel monkey revealed no overlap between SC terminals and neurons projecting to area MT. Thus, PIm is not the significant relay station of visual input from the SC to MT. The SC also sends an input to the LGN, however, this projection is sparser than the input directed to pulvinar.

Multiple Parietal–Frontal Pathways Mediate Grasping in Macaque Monkeys

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.

Somatosensory input to the ventrolateral thalamic region in the macaque monkey: A potential substrate for parkinsonian tremor

In the present study, we determined the anatomic relationships between somatosensory and motor pathways within ventrolateral (VL) thalamic nuclei of the motor thalamus of macaque monkeys. In labeling experiments, four macaque monkeys (Macaca mulatta) received injections of biotinylated dextran amine and wheat germ agglutinin conjugated to horseradish peroxidase into the cerebellar nuclei or internal segment of the globus pallidus and cervical segments of the spinal cord, respectively. Each tracer was visualized in brain sections by sequentially using a different chromogen. Labeled terminals were plotted and superimposed on adjacent brain sections processed for Nissl substance, acetylcholinesterase, and the antigens for calbindin and Cat‐301 to reveal thalamic nuclei. The labeled cerebellar terminals were distributed throughout the posterior VL (VLp), whereas the labeled pallidothalamic terminals were concentrated in the anterior VL and the ventral anterior nucleus. The spinothalamic input was directed mostly to the ventral posterior complex and cells just caudal to it. In addition, the patches of spinothalamic terminations intermingled and partly overlapped with the cerebellothalamic, but not with the pallidothalamic terminations within VLp. The regions of overlap of somatosensory and cerebellar inputs within the VLp of the present study appear to correspond to the reported locations of the tremor‐related cells in parkinsonian patients. Thus, the overlapping spinothalamic and cerebellar inputs may provide a substrate for the altered activity of motor thalamic neurons in such patients. J. Comp. Neurol. 455:378–395, 2003.