Motor actions are spatially organized in motor and dorsal premotor cortex.

Frontal motor areas are central to controlling voluntary movements. In non-human primates, the motor areas contain independent, somatotopic, representations of the forelimb (i.e.

Expression of the excitatory opsin ChRERα can be traced longitudinally in rat and nonhuman primate brains with PET imaging.

Optogenetics is a widely used technology with potential for translational research. A critical component of such applications is the ability to track the location of the transduced opsin in vivo. To address this problem, we engineered an excitatory opsin, ChRERα (hChR2(134R)-V5-ERα-LBD), that could be visualized using positron emission tomography (PET) imaging in a noninvasive, longitudinal, and quantitative manner.

Cortical connectivity is embedded in resting state at columnar resolution.

Resting state (RS) fMRI is now widely used for gaining insight into the organization of brain networks. Functional connectivity (FC) inferred from RS-fMRI is typically at macroscale, which is too coarse for much of the detail in cortical architecture. Here, we examined whether imaging RS at higher contrast and resolution could reveal cortical connectivity with columnar granularity.

Optical imaging reveals functional domains in primate sensorimotor cortex.

Motor cortex (M1) and somatosensory cortex (S1) are central to arm and hand control. Efforts to understand encoding in M1 and S1 have focused on temporal relationships between neural activity and movement features. However, it remains unclear how the neural activity is spatially organized within M1 and S1.

Principles of Intrinsic Motor Cortex Connectivity in Primates.

The forelimb representation in motor cortex (M1) is an important model system in contemporary neuroscience. Efforts to understand the organization of the M1 forelimb representation in monkeys have focused on inputs and outputs. In contrast, intrinsic M1 connections remain mostly unexplored, which is surprising given that intra-areal connections universally outnumber extrinsic connections.

Mapping mesoscale cortical connectivity in monkey sensorimotor cortex with optical imaging and microstimulation.

To map in vivo cortical circuitry at the mesoscale, we applied a novel approach to map interareal functional connectivity. Electrical intracortical microstimulation (ICMS) in conjunction with optical imaging of intrinsic signals (OIS) was used map functional connections in somatosensory cortical areas in anesthetized squirrel monkeys. ICMS produced activations that were focal and that displayed responses which were stimulation intensity dependent.

The origins of thalamic inputs to grasp zones in frontal cortex of macaque monkeys.

The hand representation in primary motor cortex (M1) is instrumental to manual dexterity in primates. In Old World monkeys, rostral and caudal aspects of the hand representation are located in the precentral gyrus and the anterior bank of the central sulcus, respectively. We previously reported the organization of the cortico-cortical connections of the grasp zone in rostral M1.

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.

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.

Effects of muscimol inactivations of functional domains in motor, premotor, and posterior parietal cortex on complex movements evoked by electrical stimulation.

Parietal and frontal cortex are central to controlling forelimb movements. We previously showed that movements such as reach, grasp, and defense can be evoked from primary motor (M1), premotor (PMC), and posterior parietal (PPC) cortex when 500-ms trains of electrical pulses are delivered via microelectrodes. Stimulation sites that evoked a specific movement clustered into domains, which shared a topographic pattern in New World monkeys and prosimian galagos.

Cortical connections to single digit representations in area 3b of somatosensory cortex in squirrel monkeys and prosimian galagos.

The ventral posterior nucleus of thalamus sends highly segregated inputs into each digit representation in area 3b of primary somatosensory cortex. However, the spatial organization of the connections that link digit representations of areas 3b with other somatosensory areas is less understood. Here we examined the cortical inputs to individual digit representations of area 3b in four squirrel monkeys and one prosimian galago.

Impairment and recovery of hand use after unilateral section of the dorsal columns of the spinal cord in squirrel monkeys.

Damage to the ascending forelimb afferents in the dorsal columns (DCs) of the cervical spinal cord in monkeys impairs forelimb use, particularly hand dexterity. Although considerable recovery has been reported, interpretation of the results is complicated by the reproducibility of the lesion and behavioral assessment. Here, we examined the effects of a unilateral DC lesion at the C4-C6 spinal cord level in four adult squirrel monkeys.

Cortical networks for ethologically relevant behaviors in primates.

Parietal-frontal networks in primate brains are central to mediating actions. Physiological and anatomical investigations have shown that the parietal-frontal network is consistently organized across several branches of primate evolution that include prosimian galagos, New World owl and squirrel monkeys, and Old World macaque monkeys. Electrical stimulation with 0.

Optical imaging in galagos reveals parietal-frontal circuits underlying motor behavior.

The posterior parietal cortex (PPC) of monkeys and prosimian galagos contains a number of subregions where complex, behaviorally meaningful movements, such as reaching, grasping, and body defense, can be evoked by electrical stimulation with long trains of electrical pulses through microelectrodes. Shorter trains of pulses evoke no or simple movements. One possibility for the difference in effectiveness of intracortical microstimulation is that long trains activate much larger regions of the brain.

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 organization and evolution of dorsal stream multisensory motor pathways in primates.

In Prosimian primates, New World monkeys, and Old World monkeys microstimulation with half second trains of electrical pulses identifies separate zones in posterior parietal cortex (PPC) where reaching, defensive, grasping, and other complex movements can be evoked. Each functional zone receives a different pattern of visual and somatosensory inputs, and projects preferentially to functionally matched parts of motor and premotor cortex. As PPC is a relatively small portion of cortex in most mammals, including the close relatives of primates, we suggest that a larger, more significant PPC emerged with the first primates as a region where several ethologically relevant behaviors could be initiated by sensory and intrinsic signals, and mediated via connections with premotor and motor cortex.

Cortical connections of functional zones in posterior parietal cortex and frontal cortex motor regions in new world monkeys.

We examined the connections of posterior parietal cortex (PPC) with motor/premotor cortex (M1/PM) and other cortical areas. Electrical stimulation (500 ms trains) delivered to microelectrode sites evoked movements of reach, defense, and grasp, from distinct zones in M1/PM and PPC, in squirrel and owl monkeys. Tracer injections into M1/PM reach, defense, and grasp zones showed dense connections with M1/PM hand/forelimb representations.

Cell-poor septa separate representations of digits in the ventroposterior nucleus of the thalamus in monkeys and prosimian galagos.

The architectonic features of the ventroposterior nucleus (VP) were visualized in coronal brain sections from two macaque monkeys, two owl monkeys, two squirrel monkeys, and three galagos that were processed for cytochrome oxidase, Nissl bodies, or the vesicular glutamate transporter 2 (vGluT2). The traditional ventroposterior medial (VPM) and ventroposterior lateral (VPL) subnuclei were easily identified, as well as the forelimb and hindlimb compartments of VPL, as they were separated by poorly staining, cell-poor septa. Septa also separated other cell groups within VPM and VPL, specifically in the medial compartment of VPL representing the hand (hand VPL).

Thalamocortical connections of functional zones in posterior parietal cortex and frontal cortex motor regions in New World monkeys.

Posterior parietal cortex (PPC) links primate visual and motor systems and is central to visually guided action. Relating the anatomical connections of PPC to its neurophysiological functions may elucidate the organization of the parietal-frontal network. In owl and squirrel monkeys, long-duration electrical stimulation distinguished several functional zones within the PPC and motor/premotor cortex (M1/PM).

Transient middle cerebral artery occlusion disrupts the forelimb movement representations of rat motor cortex.

Infarcts from proximal middle cerebral artery (MCA) stroke can produce impairments in motor function, particularly finger movements in humans and digit flexion in rats. In rats, the extent of neural damage may be limited to basal ganglia structures or may also include portions of the frontal and parietal cortex in severe cases. Although the primary motor cortex (M1) is anatomically spared in proximal MCA occlusion, its functional integrity is suspect because even a small subcortical infarct can damage neural circuits linking M1 with basal ganglia, brainstem, and spinal cord.

Thalamic connections of architectonic subdivisions of temporal cortex in grey squirrels (Sciurus carolinensis).

The temporal cortex of grey squirrels contains three architectonically distinct regions. One of these regions, the temporal anterior (Ta) region has been identified in previous physiological and anatomical studies as containing several areas that are largely auditory in function. Consistent with this evidence, Ta has architectonic features that are internally somewhat variable, but overall sensory in nature.

Recovery of skilled reaching following motor cortex stroke: do residual corticofugal fibers mediate compensatory recovery?

Motor cortex (MC) injury impairs skilled reaching in rats, but success scores are eventually restored to approximate preoperative levels. The improvement is attributed to compensatory strategies, such as substituting trunk rotations for the chronically lost rotatory movement of the forelimb, that occur during transport and withdrawal. The present study examined the contributions of the rostral motor cortex (RMC) and the caudal motor cortex (CMC) to skilled reaching performance.

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.

Attempt-dependent decrease in skilled reaching characterizes the acute postsurgical period following a forelimb motor cortex lesion: an experimental demonstration of learned nonuse in the rat.

The notion that shock or diaschisis is a distinctive stage in the recovery process following brain damage has played a formative role in the characterization of brain injury. For example, damage to the forelimb region of motor cortex results in an acute period of behavioural depression in skilled reaching and other skilled actions followed by improved performance mediated by compensatory movements. Whereas the progression of improvement and the use of compensatory movements in the chronic period of recovery is well-documented, temporal aspects of behaviour during the acute period of depression of behaviour are relatively unstudied.

Parallel stages of learning and recovery of skilled reaching after motor cortex stroke: "oppositions" organize normal and compensatory movements.

Forelimb/hand motor cortex injury in rodents and primates causes impairments in skilled paw/hand movements that includes a period of movement absence followed by functional recovery/compensation. Although the postsurgical period of movement absence has been attributed to "shock" or "diaschisis", the behavior of animals during this period has not been fully described. Here, rats were trained to reach for single food pellets from a shelf and then the vasculature of the forelimb region of the sensorimotor cortex contralateral to the reaching limb was removed.