Model-based parcellation of diffusion MRI of injured spinal cord predicts hand use impairment and recovery in squirrel monkeys.

A mathematical model-based parcellation of magnetic resonance diffusion tensor images (DTI) has been developed to quantify progressive changes in three types of tissues - grey (GM), white matter (WM), and damaged spinal cord tissue, along with behavioral assessments over a 6 month period following targeted spinal cord injuries (SCI) in monkeys. Sigmoid Gompertz function based fittings of DTI metrics provide early indicators that correlate with, and predict, recovery of hand grasping behavior. Our three tissue pool model provided unbiased, data-driven segmentation of spinal cord images and identified DTI metrics that can serve as reliable biomarkers of severity of spinal cord injuries and predictors of behavioral outcomes.

The postnatal development of retinal projections in strepsirrhine galagos (Otolemur garnettii).

Here, we describe the postnatal development of retinal projections in galagos. Galagos are of special interest as they represent the understudied strepsirrhine branch (galagos, pottos, lorises, and lemurs) of the primate radiations. The projections of both eyes were revealed in each galago by injecting red or green cholera toxin subunit B (CTB) tracers into different eyes of galagos ranging from postnatal day 5 to adult.

Regressive changes in sizes of somatosensory cuneate nucleus after sensory loss in primates.

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.

Escaping the nocturnal bottleneck, and the evolution of the dorsal and ventral streams of visual processing in primates.

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.

Longitudinal fMRI measures of cortical reactivation and hand use with and without training after sensory loss in primates.

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.

Corticocuneate projections are altered after spinal cord dorsal column lesions in New World monkeys.

Recovery of responses to cutaneous stimuli in the area 3b hand cortex of monkeys after dorsal column lesions (DCLs) in the cervical spinal cord relies on neural rewiring in the cuneate nucleus (Cu) over time. To examine whether the corticocuneate projections are modified during recoveries after the DCL, we injected cholera toxin subunit B into the hand representation in Cu to label the cortical neurons after various recovery times, and related results to the recovery of neural responses in the affected area 3b hand cortex. In normal New World monkeys, labeled neurons were predominately distributed in the hand regions of contralateral areas 3b, 3a, 1 and 2, parietal ventral (PV), secondary somatosensory cortex (S2), and primary motor cortex (M1), with similar distributions in the ipsilateral cortex in significantly smaller numbers.

Reorganization of Higher-Order Somatosensory Cortex After Sensory Loss from Hand in Squirrel Monkeys.

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.

Second-order spinal cord pathway contributes to cortical responses after long recoveries from dorsal column injury in squirrel monkeys.

Months after the occurrence of spinal cord dorsal column lesions (DCLs) at the cervical level, neural responses in the hand representation of somatosensory area 3b hand cortex recover, along with hand use. To examine whether the second-order spinal cord pathway contributes to this functional recovery, we injected cholera toxin subunit B (CTB) into the hand representation in the cuneate nucleus (Cu) to label the spinal cord neurons, and related results to cortical reactivation in four squirrel monkeys () at least 7 months after DCL. In two monkeys with complete DCLs, few CTB-labeled neurons were present below the lesion, and few neurons in the affected hand region in area 3b responded to touch on the hand.

The evolution of parietal cortex in primates.

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.

Plasticity and Recovery After Dorsal Column Spinal Cord Injury in Nonhuman Primates.

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.

Spatiotemporal trajectories of reactivation of somatosensory cortex by direct and secondary pathways after dorsal column lesions in squirrel monkeys.

After lesions of the somatosensory dorsal column (DC) pathway, the cortical hand representation can become unresponsive to tactile stimuli, but considerable responsiveness returns over weeks of post-lesion recovery. The reactivation suggests that preserved subthreshold sensory inputs become potentiated and axon sprouting occurs over time to mediate recovery. Here, we studied the recovery process in 3 squirrel monkeys, using high-resolution cerebral blood volume-based functional magnetic resonance imaging (CBV-fMRI) mapping of contralateral somatosensory cortex responsiveness to stimulation of distal finger pads with low and high level electrocutaneous stimulation (ES) before and 2, 4, and 6weeks after a mid-cervical level contralateral DC lesion.

Chronic recordings reveal tactile stimuli can suppress spontaneous activity of neurons in somatosensory cortex of awake and anesthetized primates.

In somatosensory cortex, tactile stimulation within the neuronal receptive field (RF) typically evokes a transient excitatory response with or without postexcitatory inhibition. Here, we describe neuronal responses in which stimulation on the hand is followed by suppression of the ongoing discharge. With the use of 16-channel microelectrode arrays implanted in the hand representation of primary somatosensory cortex of New World monkeys and prosimian galagos, we recorded neuronal responses from single units and neuron clusters.

Intracortical connections are altered after long-standing deprivation of dorsal column inputs in the hand region of area 3b in squirrel monkeys.

A complete unilateral lesion of the dorsal column somatosensory pathway in the upper cervical spinal cord deactivates neurons in the hand region in contralateral somatosensory cortex (areas 3b and 1). Over weeks to months of recovery, parts of the hand region become reactivated by touch on the hand or face. To determine whether changes in cortical connections potentially contribute to this reactivation, we injected tracers into electrophysiologically identified locations in cortex of area 3b representing the reactivated hand and normally activated face in adult squirrel monkeys.

Subcortical barrelette-like and barreloid-like structures in the prosimian galago (Otolemur garnetti).

Galagos are prosimian primates that resemble ancestral primates more than most other extant primates. As in many other mammals, the facial vibrissae of galagos are distributed across the upper and lower jaws and above the eye. In rats and mice, the mystacial macrovibrissae are represented throughout the ascending trigeminal pathways as arrays of cytoarchitecturally distinct modules, with each module having a nearly one-to-one relationship with a specific facial whisker.

Spinal cord neuron inputs to the cuneate nucleus that partially survive dorsal column lesions: A pathway that could contribute to recovery after spinal cord injury.

Dorsal column lesions at a high cervical level deprive the cuneate nucleus and much of the somatosensory system of its major cutaneous inputs. Over weeks of recovery, much of the hand representations in the contralateral cortex are reactivated. One possibility for such cortical reactivation by hand afferents is that preserved second-order spinal cord neurons reach the cuneate nucleus through pathways that circumvent the dorsal column lesions, contributing to cortical reactivation in an increasingly effective manner over time.

Multiparametric MRI reveals dynamic changes in molecular signatures of injured spinal cord in monkeys.

Purpose: To monitor the spontaneous recovery of cervical spinal cord injury (SCI) using longitudinal multiparametric MRI methods.

Methods: Quantitative MRI imaging including diffusion tensor imaging, magnetization transfer (MT), and chemical exchange saturation transfer (CEST) were conducted in anesthetized squirrel monkeys at 9.4T.

Congenital foot deformation alters the topographic organization in the primate somatosensory system.

Limbs may fail to grow properly during fetal development, but the extent to which such growth alters the nervous system has not been extensively explored. Here we describe the organization of the somatosensory system in a 6-year-old monkey (Macaca radiata) born with a deformed left foot in comparison to the results from a normal monkey (Macaca fascicularis). Toes 1, 3, and 5 were missing, but the proximal parts of toes 2 and 4 were present.

Parallel functional reorganizations of somatosensory areas 3b and 1, and S2 following spinal cord injury in squirrel monkeys.

Multiple somatosensory cortices of adult primates reorganize following spinal cord injury, but little is known about the temporal dynamics and inter-areal differences of the reorganization. Using longitudinal high-resolution fMRI in combination with microelectrode recordings and tracer histology, we previously illustrated a two-phase dynamic spatial reorganization of digit representations in area 3b within weeks after a unilateral lesion of the dorsal column in squirrel monkeys (Chen et al., 2012).

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

In our experiments, we removed a major source of activation of somatosensory cortex in mature monkeys by unilaterally sectioning the sensory afferents in the dorsal columns of the spinal cord at a high cervical level. At this level, the ascending branches of tactile afferents from the hand are cut, while other branches of these afferents remain intact to terminate on neurons in the dorsal horn of the spinal cord. Immediately after such a lesion, the monkeys seem relatively unimpaired in locomotion and often use the forelimb, but further inspection reveals that they prefer to use the unaffected hand in reaching for food.

Cortical neuron response properties are related to lesion extent and behavioral recovery after sensory loss from spinal cord injury in monkeys.

Lesions of the dorsal columns at a mid-cervical level render the hand representation of the contralateral primary somatosensory cortex (area 3b) unresponsive. Over weeks of recovery, most of this cortex becomes responsive to touch on the hand. Determining functional properties of neurons within the hand representation is critical to understanding the neural basis of this adaptive plasticity.

Functional signature of recovering cortex: dissociation of local field potentials and spiking activity in somatosensory cortices of spinal cord injured monkeys.

After disruption of dorsal column afferents at high cervical spinal levels in adult monkeys, somatosensory cortical neurons recover responsiveness to tactile stimulation of the hand; this reactivation correlates with a recovery of hand use. However, it is not known if all neuronal response properties recover, and whether different cortical areas recover in a similar manner. To address this, we recorded neuronal activity in cortical area 3b and S2 in adult squirrel monkeys weeks after unilateral lesion of the dorsal columns.

Thalamic input to representations of the teeth, tongue, and face in somatosensory area 3b of macaque monkeys.

Representations of the parts of the oral cavity and face in somatosensory area 3b of macaque monkeys were identified with microelectrode recordings and injected with different neuroanatomical tracers to reveal patterns of thalamic projections to tongue, teeth, and other representations in primary somatosensory cortex. The locations of injection sites and resulting labeled neurons were further determined by relating sections processed to reveal tracers to those processed for myeloarchitecture in the cortex and multiple architectural stains in the thalamus. The ventroposterior medial subnucleus (VPM) for touch was identified as separate from the ventroposterior medial parvicellular nucleus (VPMpc) for taste by differential expression of several types of proteins.

Corticocortical projections to representations of the teeth, tongue, and face in somatosensory area 3b of macaques.

We placed injections of anatomical tracers into representations of the tongue, teeth, and face in the primary somatosensory cortex (area 3b) of macaque monkeys. Our injections revealed strong projections to representations of the tongue and teeth from other parts of the oral cavity responsive region in 3b. The 3b face also provided input to the representations of the intraoral structures.