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BACKGROUND: Infancy is characterized by rapid neurological transformations leading to consolidation of lifelong function capabilities. Studying the infant brain is crucial for understanding how these mechanisms develop during this sensitive period. We review the neuroimaging modalities used with infants in stimulus-induced activity paradigms specifically, for the unique opportunity the latter provide for assessment of brain function. METHODS: Conducted a systematic review of literature published between 1977-2021, via a comprehensive search of four major databases. Standardized appraisal tools and inclusion/exclusion criteria were set according to the PRISMA guidelines. RESULTS: Two-hundred and thirteen papers met the criteria of the review process. The results show clear evidence of overall cumulative growth in the number of infant functional neuroimaging studies, with electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) to be the most utilized and fastest growing modalities with behaving infants. However, there is a high level of exclusion rates associated with technical limitations, leading to limited motor control studies (about 6%) in this population. CONCLUSION: Although the use of functional neuroimaging modalities with infants increases, there are impediments to effective adoption of existing technologies with this population. Developing new imaging modalities and experimental designs to monitor brain activity in awake and behaving infants is vital.

Basal ganglia play a central role in regulating behavior, but the organization of their outputs to other brain areas is incompletely understood. We investigate the largest output nucleus, the substantia nigra pars reticulata (SNr), and delineate the organization and physiology of its projection populations in mice. Using genetically targeted viral tracing and whole-brain anatomical analysis, we identify over 40 SNr targets that encompass a roughly 50-fold range of axonal densities. Retrograde tracing from the volumetrically largest targets indicates that the SNr contains segregated subpopulations that differentially project to functionally distinct brain stem regions. These subpopulations are electrophysiologically specialized and topographically organized and collateralize to common diencephalon targets, including the motor and intralaminar thalamus as well as the pedunculopontine nucleus and the midbrain reticular formation. These findings establish that SNr signaling is organized as dense, parallel outputs to specific brain stem targets concurrent with extensive collateral branches that encompass the majority of SNr axonal boutons.

Electrical stimulation is a promising tool for modulating brain networks. However, it is unclear how stimulation interacts with neural patterns underlying behavior. Specifically, how might external stimulation that is not sensitive to the state of ongoing neural dynamics reliably augment neural processing and improve function? Here, we tested how low-frequency epidural alternating current stimulation (ACS) in non-human primates recovering from stroke interacted with task-related activity in perilesional cortex and affected grasping. We found that ACS increased co-firing within task-related ensembles and improved dexterity. Using a neural network model, we found that simulated ACS drove ensemble co-firing and enhanced propagation of neural activity through parts of the network with impaired connectivity, suggesting a mechanism to link increased co-firing to enhanced dexterity. Together, our results demonstrate that ACS restores neural processing in impaired networks and improves dexterity following stroke. More broadly, these results demonstrate approaches to optimize stimulation to target neural dynamics.

In this article, we review recent advances in research on rhythm and musical beat perception, focusing on the role of predictive processes in auditory motor interactions. We suggest that experimental evidence of the motor system's role in beat perception, including in passive listening, may be explained by the generation and maintenance of internal predictive models, concordant with the Active Inference framework of sensory processing. We highlight two complementary hypotheses for the neural underpinnings of rhythm perception: The Action Simulation for Auditory Prediction hypothesis (Patel and Iversen, 2014) and the Gradual Audiomotor Evolution hypothesis (Merchant and Honing, 2014) and review recent experimental progress supporting each of these hypotheses. While initial formulations of ASAP and GAE explain different aspects of beat-based timing-the involvement of motor structures in the absence of movement, and physical entrainment to an auditory beat respectively-we suggest that work under both hypotheses provide converging evidence toward understanding the predictive role of the motor system in the perception of rhythm, and the specific neural mechanisms involved. We discuss future experimental work necessary to further evaluate the causal neural mechanisms underlying beat and rhythm perception.

A central goal of neuroscience is to understand how populations of neurons coordinate and cooperate in order to give rise to perception, cognition, and action. Nonhuman primates (NHPs) are an attractive model with which to understand these mechanisms in humans, primarily due to the strong homology of their brains and the cognitively sophisticated behaviors they can be trained to perform. Using electrode recordings, the activity of one to a few hundred individual neurons may be measured electrically, which has enabled many scientific findings and the development of brain-machine interfaces. Despite these successes, electrophysiology samples sparsely from neural populations and provides little information about the genetic identity and spatial micro-organization of recorded neurons. These limitations have spurred the development of all-optical methods for neural circuit interrogation. Fluorescent calcium signals serve as a reporter of neuronal responses, and when combined with post-mortem optical clearing techniques such as CLARITY, provide dense recordings of neuronal populations, spatially organized and annotated with genetic and anatomical information. Here, we advocate that this methodology, which has been of tremendous utility in smaller animal models, can and should be developed for use with NHPs. We review here several of the key opportunities and challenges for calcium-based optical imaging in NHPs. We focus on motor neuroscience and brain-machine interface design as representative domains of opportunity within the larger field of NHP neuroscience.

Optimal control models of biological movements introduce external task factors to specify the pace of movements. Here, we present the dual to the principle of optimality based on a conserved quantity, called "drive," that represents the influence of internal motivation level on movement pace. Optimal control and drive conservation provide equivalent descriptions for the regularities observed within individual movements. For regularities across movements, drive conservation predicts a previously unidentified scaling law between the overall size and speed of various self-paced hand movements in the absence of any external tasks, which we confirmed with psychophysical experiments. Drive can be interpreted as a high-level control variable that sets the overall pace of movements and may be represented in the brain as the tonic levels of neuromodulators that control the level of internal motivation, thus providing insights into how internal states affect biological motor control.

Targeted deletion of the phosphatase and tensin homolog on chromosome ten (PTEN) gene in the sensorimotor cortex of neonatal mice enables robust regeneration of corticospinal tract (CST) axons following spinal cord injury as adults. Here, we assess the consequences of long-term conditional genetic PTEN deletion on cortical structure and neuronal morphology and screen for neuropathology. Mice with a LoxP-flanked exon 5 of the PTEN gene (PTENf/f mice) received AAV-Cre injections into the sensorimotor cortex at postnatal day 1 (P1) and were allowed to survive for up to 18months. As adults, mice were assessed for exploratory activity (open field), and motor coordination using the Rotarod®. Some mice received injections of Fluorogold into the spinal cord to retrogradely label the cells of origin of the CST. Brains were prepared for neurohistology and immunostained for PTEN and phospho-S6, which is a downstream marker of mammalian target of rapamycin (mTOR) activation. Immunostaining revealed a focal area of PTEN deletion affecting neurons in all cortical layers, although in some cases PTEN expression was maintained in many small-medium sized neurons in layers III-IV. Neurons lacking PTEN were robustly stained for pS6. Cortical thickness was significantly increased and cortical lamination was disrupted in the area of PTEN deletion. PTEN-negative layer V neurons that give rise to the CST, identified by retrograde labeling, were larger than neurons with maintained PTEN expression, and the relative area occupied by neuropil vs. cell bodies was increased. There was no evidence of tumor formation or other neuropathology. Mice with PTEN deletion exhibited open field activity comparable to controls and there was a trend for impaired Rotarod performance (not statistically significant). Our findings indicate that early postnatal genetic deletion of PTEN that is sufficient to enable axon regeneration by adult neurons causes neuronal hypertrophy but no other detectable neuropathology.

Targeted deletion of the phosphatase and tensin homolog on chromosome ten (PTEN) gene in the sensorimotor cortex of neonatal mice enables robust regeneration of corticospinal tract (CST) axons following spinal cord injury as adults. Here, we assess the consequences of long-term conditional genetic PTEN deletion on cortical structure and neuronal morphology and screen for neuropathology. Mice with a LoxP-flanked exon 5 of the PTEN gene (PTENf/f mice) received AAV-Cre injections into the sensorimotor cortex at postnatal day 1 (P1) and were allowed to survive for up to 18months. As adults, mice were assessed for exploratory activity (open field), and motor coordination using the Rotarod®. Some mice received injections of Fluorogold into the spinal cord to retrogradely label the cells of origin of the CST. Brains were prepared for neurohistology and immunostained for PTEN and phospho-S6, which is a downstream marker of mammalian target of rapamycin (mTOR) activation. Immunostaining revealed a focal area of PTEN deletion affecting neurons in all cortical layers, although in some cases PTEN expression was maintained in many small-medium sized neurons in layers III-IV. Neurons lacking PTEN were robustly stained for pS6. Cortical thickness was significantly increased and cortical lamination was disrupted in the area of PTEN deletion. PTEN-negative layer V neurons that give rise to the CST, identified by retrograde labeling, were larger than neurons with maintained PTEN expression, and the relative area occupied by neuropil vs. cell bodies was increased. There was no evidence of tumor formation or other neuropathology. Mice with PTEN deletion exhibited open field activity comparable to controls and there was a trend for impaired Rotarod performance (not statistically significant). Our findings indicate that early postnatal genetic deletion of PTEN that is sufficient to enable axon regeneration by adult neurons causes neuronal hypertrophy but no other detectable neuropathology.

Rodent models of spinal cord injury are critical for the development of treatments for upper limb motor impairment in humans, but there are few methods for measuring forelimb strength of rodents, an important outcome measure. We developed a novel robotic device--the Robotic Rehabilitator of the Rodent Upper Extremity (RUE)--that requires rats to voluntarily reach for and pull a bar to retrieve a food reward; the resistance of the bar can be programmed. We used RUE to train forelimb strength of 16 rats three times per week for 23 weeks before and 38 weeks after a mild (100 kdyne) unilateral contusion at the cervical level 5 (C5). We measured maximum force produced when RUE movement was unexpectedly blocked. We compared this blocked pulling force (BPF) to weekly measures of forelimb strength obtained with a previous, well-established method: the grip strength meter (GSM). Before injury, BPF was 2.6 times higher (BPF, 444.6 ± 19.1 g; GSM, 168.4 ± 3.1 g) and 4.9 times more variable (p < 0.001) than pulling force measured with the GSM; the two measurement methods were uncorrelated (R(2) = 0.03; p = 0.84). After injury, there was a significant decrease in BPF of 134.35 g ± 14.71 g (p < 0.001). Together, our findings document BPF as a repeatable measure of forelimb force production, sensitive to a mild spinal cord injury, which comes closer to measuring maximum force than the GSM and thus may provide a useful measure for quantifying the effects of treatment in rodent models of SCI.

In a planar free-hand drawing of an ellipse, the speed of movement is proportional to the -1/3 power of the local curvature, which is widely thought to hold for general curved shapes. We investigated this phenomenon for general curved hand movements by analyzing an optimal control model that maximizes a smoothness cost and exhibits the -1/3 power for ellipses. For the analysis, we introduced a new representation for curved movements based on a moving reference frame and a dimensionless angle coordinate that revealed scale-invariant features of curved movements. The analysis confirmed the power law for drawing ellipses but also predicted a spectrum of power laws with exponents ranging between 0 and -2/3 for simple movements that can be characterized by a single angular frequency. Moreover, it predicted mixtures of power laws for more complex, multifrequency movements that were confirmed with human drawing experiments. The speed profiles of arbitrary doodling movements that exhibit broadband curvature profiles were accurately predicted as well. These findings have implications for motor planning and predict that movements only depend on one radian of angle coordinate in the past and only need to be planned one radian ahead.

Previous studies indicate that conditional genetic deletion of phosphatase and tensin homolog (PTEN) in neonatal mice enhances the ability of axons to regenerate following spinal cord injury (SCI) in adults. Here, we assessed whether deleting PTEN in adult neurons post-SCI is also effective, and whether enhanced regenerative growth is accompanied by enhanced recovery of voluntary motor function. PTEN(loxP/loxP) mice received moderate contusion injuries at cervical level 5 (C5). One group received unilateral injections of adeno-associated virus expressing CRE (AAV-CRE) into the sensorimotor cortex; controls received a vector expressing green fluorescent protein (AAV-GFP) or injuries only (no vector injections). Forelimb function was tested for 14weeks post-SCI using a grip strength meter (GSM) and a hanging task. The corticospinal tract (CST) was traced by injecting mini-ruby BDA into the sensorimotor cortex. Forelimb gripping ability was severely impaired immediately post-SCI but recovered slowly over time. The extent of recovery was significantly greater in PTEN-deleted mice in comparison to either the AAV-GFP group or the injury only group. BDA tract tracing revealed significantly higher numbers of BDA-labeled axons in caudal segments in the PTEN-deleted group compared to control groups. In addition, in the PTEN-deleted group, there were exuberant collaterals extending from the main tract rostral to the lesion and into and around the scar tissue at the injury site. These results indicate that PTEN deletion in adult mice shortly post-SCI can enhance regenerative growth of CST axons and forelimb motor function recovery.

Behavior is derived from the configuration of synaptic connectivity among functionally diverse neurons. Fine motor behavior is absent at birth in most mammals but gradually emerges during subsequent postnatal corticospinal system maturation; the nature of circuit development and reorganization during this period has been largely unexplored. We investigated connectivity and synaptic signaling among functionally distinct corticospinal populations in Fischer 344 rats from postnatal day 18 through 75 using retrograde tracer injections into specific spinal cord segments associated with distinct aspects of forelimb function. Primary motor cortex slices were prepared enabling simultaneous patch-clamp recordings of up to four labeled corticospinal neurons and testing of 3489 potential synaptic connections. We find that, in immature animals, local connectivity is biased toward corticospinal neurons projecting to the same spinal cord segment; this within-population connectivity significantly decreases through maturation until connection frequency is similar between neurons projecting to the same (within-population) or different (across-population) spinal segments. Concomitantly, postnatal maturation is associated with a significant reduction in synaptic efficacy over time and an increase in intrinsic neuronal excitability, altering how excitation is effectively transmitted across recurrent corticospinal networks. Collectively, the postnatal emergence of fine motor control is associated with a relative broadening of connectivity between functionally diverse cortical motor neurons and changes in synaptic properties that could enable the emergence of smaller independent networks, enabling fine motor movement. These changes in synaptic patterning and physiological function provide a basis for the increased capabilities of the mature versus developing brain.

Subtle changes in motor function have been observed in individuals with prodromal Huntington disease (prHD), but the underlying neural mechanisms are not well understood nor is the cumulative effect of the disease (disease burden) on functional connectivity. The present study examined the resting-state functional magnetic resonance imaging (rs-fMRI) connectivity of the primary motor cortex (M1) in 16 gene-negative (NEG) controls and 48 gene-positive prHD participants with various levels of disease burden. The results showed that the strength of the left M1 connectivity with the ipsilateral M1 and somatosensory areas decreased as disease burden increased and correlated with motor symptoms. Weakened M1 connectivity within the motor areas was also associated with abnormalities in long-range connections that evolved with disease burden. In this study, M1 connectivity was decreased with visual centers (bilateral cuneus), but increased with a hub of the default mode network (DMN; posterior cingulate cortex). Changes in connectivity measures were associated with worse performance on measures of cognitive-motor functioning. Short- and long-range functional connectivity disturbances were also associated with volume loss in the basal ganglia, suggesting that weakened M1 connectivity is partly a manifestation of striatal atrophy. Altogether, the results indicate that the prodromal phase of HD is associated with abnormal interhemispheric interactions among motor areas and disturbances in the connectivity of M1 with visual centers and the DMN. These changes may, respectively, contribute to increased motor symptoms, visuomotor integration problems, and deficits in the executive control of movement as individuals approach a manifest diagnosis.

As part of the NIH "Facilities of Research Excellence-Spinal Cord Injury" project to support independent replication, we repeated key parts of a study reporting robust engraftment of neural stem cells (NSCs) treated with growth factors after complete spinal cord transection in rats. Rats (n=20) received complete transections at thoracic level 3 (T3) and 2weeks later received NSC transplants in a fibrin matrix with a growth factor cocktail using 2 different transplantation methods (with and without removal of scar tissue). Control rats (n=9) received transections only. Hindlimb locomotor function was assessed with the BBB scale. Nine weeks post injury, reticulospinal tract axons were traced in 6 rats by injecting BDA into the reticular formation. Transplants grew to fill the lesion cavity in most rats although grafts made with scar tissue removal had large central cavities. Grafts blended extensively with host tissue obliterating the astroglial boundary at the cut ends, but in most cases there was a well-defined partition within the graft that separated rostral and caudal parts of the graft. In some cases, the partition contained non-neuronal scar tissue. There was extensive outgrowth of GFP labeled axons from the graft, but there was minimal ingrowth of host axons into the graft revealed by tract tracing and immunocytochemistry for 5HT. There were no statistically significant differences between transplant and control groups in the degree of locomotor recovery. Our results confirm the previous report that NSC transplants can fill lesion cavities and robustly extend axons, but reveal that most grafts do not create a continuous bridge of neural tissue between rostral and caudal segments.

Many different measures have been found to be related to behavioral outcome after stroke. Preclinical studies emphasize the importance of brain injury and neural function. However, the measures most important to human outcomes remain uncertain, in part because studies often examine one measure at a time or enroll only mildly impaired patients. The current study addressed this by performing multimodal evaluation in a heterogeneous population. Patients (n = 36) with stable arm paresis 3-6 months post-stroke were assessed across 6 categories of measures related to stroke outcome: demographics/medical history, cognitive/mood status, genetics, neurophysiology, brain injury, and cortical function. Multivariate modeling identified measures independently related to an impairment-based outcome (arm Fugl-Meyer motor score). Analyses were repeated (1) identifying measures related to disability (modified Rankin Scale score), describing independence in daily functions and (2) using only patients with mild deficits. Across patients, greater impairment was related to measures of injury (reduced corticospinal tract integrity) and neurophysiology (absence of motor evoked potential). In contrast, (1) greater disability was related to greater injury and poorer cognitive status (MMSE score) and (2) among patients with mild deficits, greater impairment was related to cortical function (greater contralesional motor/premotor cortex activation). Impairment after stroke is most related to injury and neurophysiology, consistent with preclinical studies. These relationships vary according to the patient subgroup or the behavioral endpoint studied. One potential implication of these results is that choice of biomarker or stratifying variable in a clinical stroke study might vary according to patient characteristics.

Many different measures have been found to be related to behavioral outcome after stroke. Preclinical studies emphasize the importance of brain injury and neural function. However, the measures most important to human outcomes remain uncertain, in part because studies often examine one measure at a time or enroll only mildly impaired patients. The current study addressed this by performing multimodal evaluation in a heterogeneous population. Patients (n = 36) with stable arm paresis 3-6 months post-stroke were assessed across 6 categories of measures related to stroke outcome: demographics/medical history, cognitive/mood status, genetics, neurophysiology, brain injury, and cortical function. Multivariate modeling identified measures independently related to an impairment-based outcome (arm Fugl-Meyer motor score). Analyses were repeated (1) identifying measures related to disability (modified Rankin Scale score), describing independence in daily functions and (2) using only patients with mild deficits. Across patients, greater impairment was related to measures of injury (reduced corticospinal tract integrity) and neurophysiology (absence of motor evoked potential). In contrast, (1) greater disability was related to greater injury and poorer cognitive status (MMSE score) and (2) among patients with mild deficits, greater impairment was related to cortical function (greater contralesional motor/premotor cortex activation). Impairment after stroke is most related to injury and neurophysiology, consistent with preclinical studies. These relationships vary according to the patient subgroup or the behavioral endpoint studied. One potential implication of these results is that choice of biomarker or stratifying variable in a clinical stroke study might vary according to patient characteristics.

Cerebral control of foot movements has received limited study. Functional MRI compared slow with rapid foot movement, and right (dominant) with left foot movement. Brain activation during right, as compared with left, foot movement was larger, with higher amplitude task-related motor cortex signal change, and higher laterality index. Brain activation during fast, as compared with slow, foot movement was larger in cortical and cerebellar areas but smaller in deep gray areas. Some principles of cerebral control of hand movement extend to foot, but exceptions found include that dominant foot movement showed greater activation than did nondominant, and faster foot movements activated bilateral deep gray matter structures less than did slower. Results might have utility in trials of restorative therapies.

Cerebral control of foot movements has received limited study. Functional MRI compared slow with rapid foot movement, and right (dominant) with left foot movement. Brain activation during right, as compared with left, foot movement was larger, with higher amplitude task-related motor cortex signal change, and higher laterality index. Brain activation during fast, as compared with slow, foot movement was larger in cortical and cerebellar areas but smaller in deep gray areas. Some principles of cerebral control of hand movement extend to foot, but exceptions found include that dominant foot movement showed greater activation than did nondominant, and faster foot movements activated bilateral deep gray matter structures less than did slower. Results might have utility in trials of restorative therapies.

Evidence suggests that executed, imagined, and observed movements share neural substrates, however, brain activation during the performance of these three tasks has not yet been examined during lower extremity movements. Functional MRI was performed in 10 healthy right-footed participants during imagined, executed, and observed right ankle movements. Task compliance was high, confirmed via behavioral assessment and electromyographic measurements. Each task was also associated with its own profile of regional activation, however, overall, regional activation showed substantial overlap across the three lower extremity motor tasks. The findings suggest the utility of continued efforts to develop motor imagery and observation programs for improving lower extremity function in a range of clinical settings.

Evidence suggests that executed, imagined, and observed movements share neural substrates, however, brain activation during the performance of these three tasks has not yet been examined during lower extremity movements. Functional MRI was performed in 10 healthy right-footed participants during imagined, executed, and observed right ankle movements. Task compliance was high, confirmed via behavioral assessment and electromyographic measurements. Each task was also associated with its own profile of regional activation, however, overall, regional activation showed substantial overlap across the three lower extremity motor tasks. The findings suggest the utility of continued efforts to develop motor imagery and observation programs for improving lower extremity function in a range of clinical settings.

The study of stroke and its treatment in human subjects requires accurate measurement of behavioral status. Arm motor deficits are among the most common sequelae after stroke. The Action Research Arm Test (ARAT) is a reliable, valid measure of arm motor status after stroke. This test has established value for characterizing clinical state and for measuring spontaneous and therapy-induced recovery; however, sufficient details have not been previously published to allow for performance of this scale in a standardized manner over time and across sites. Such an approach to ARAT scoring would likely reduce variance between investigators and sites. This report therefore includes a manual that provides a highly detailed and standardized approach for assigning ARAT scores. Intrarater reliability and interrater reliability, as well as validity, with this approach were measured and are excellent. The ARAT, when performed in a standardized manner, is a useful tool for assessment of arm motor deficits after stroke.

The study of stroke and its treatment in human subjects requires accurate measurement of behavioral status. Arm motor deficits are among the most common sequelae after stroke. The Action Research Arm Test (ARAT) is a reliable, valid measure of arm motor status after stroke. This test has established value for characterizing clinical state and for measuring spontaneous and therapy-induced recovery; however, sufficient details have not been previously published to allow for performance of this scale in a standardized manner over time and across sites. Such an approach to ARAT scoring would likely reduce variance between investigators and sites. This report therefore includes a manual that provides a highly detailed and standardized approach for assigning ARAT scores. Intrarater reliability and interrater reliability, as well as validity, with this approach were measured and are excellent. The ARAT, when performed in a standardized manner, is a useful tool for assessment of arm motor deficits after stroke.

Abnormalities in brain motor system function are present following spinal cord injury (SCI) and could reduce effectiveness of restorative interventions. Motor imagery training, which can improve motor behavior and modulate brain function, might address this concern but has not been examined in subjects with SCI. Ten subjects with SCI and complete tetra-/paraplegia plus ten healthy controls underwent assessment before and after 7 days of motor imagery training to tongue and to foot. Motor imagery training significantly improved the behavioral outcome measure, speed of movement, in non-paralyzed muscles. Training was also associated with increased fMRI activation in left putamen, an area associated with motor learning, during attempted right foot movement in both groups, despite foot movements being present in controls and absent in subjects with SCI. This fMRI change was absent in a second healthy control group serially imaged without training. In subjects with SCI, training exaggerated, rather than normalized, baseline derangement of left globus pallidus activation. The current study found that motor imagery training improves motor performance and alters brain function in subjects with complete SCI despite lack of voluntary motor control and peripheral feedback. These effects of motor imagery training on brain function have not been previously described in a neurologically impaired population, and were similar to those found in healthy controls. Motor imagery might be of value as one component of a restorative intervention.

Abnormalities in brain motor system function are present following spinal cord injury (SCI) and could reduce effectiveness of restorative interventions. Motor imagery training, which can improve motor behavior and modulate brain function, might address this concern but has not been examined in subjects with SCI. Ten subjects with SCI and complete tetra-/paraplegia plus ten healthy controls underwent assessment before and after 7 days of motor imagery training to tongue and to foot. Motor imagery training significantly improved the behavioral outcome measure, speed of movement, in non-paralyzed muscles. Training was also associated with increased fMRI activation in left putamen, an area associated with motor learning, during attempted right foot movement in both groups, despite foot movements being present in controls and absent in subjects with SCI. This fMRI change was absent in a second healthy control group serially imaged without training. In subjects with SCI, training exaggerated, rather than normalized, baseline derangement of left globus pallidus activation. The current study found that motor imagery training improves motor performance and alters brain function in subjects with complete SCI despite lack of voluntary motor control and peripheral feedback. These effects of motor imagery training on brain function have not been previously described in a neurologically impaired population, and were similar to those found in healthy controls. Motor imagery might be of value as one component of a restorative intervention.

Stroke has been associated with many changes in motor system function, but there has been limited study of changes in somatotopic organization. This was examined in a group of patients with cortical stroke affecting primary sensorimotor cortex. In 17 patients with good outcome after cortical stroke involving precentral and/or postcentral gyri, plus 14 controls, four functional MRI evaluations of brain activity were obtained: finger, shoulder, and face motor tasks plus a sensory task, passive finger motion. For each, coordinates for contralateral primary sensorimotor cortex activation site were determined, as was a measure of inter-hemispheric balance. The normal motor somatotopy measured in controls was largely preserved after stroke. The main difference found between controls and patients was that the face was lateral to finger motor activation in all controls, but face was centered medial to finger in 43% of patients. Among patients, smaller infarct volume was associated with more ventral, and larger infarct with more dorsal, contralateral primary sensorimotor cortex activation. On the other hand, better behavioral outcome was associated with a more posterior, and poorer outcome with more anterior, activation. Larger infarct and poorer behavioral outcome were each associated with a change in inter-hemispheric balance towards the non-stroke hemisphere. Shifts in contralateral movement representation site did not correlate with changes in inter-hemispheric balance. Motor somatotopy is generally preserved after injury to primary sensorimotor cortex. Greater injury and larger behavioral deficits are associated with distinct effects on movement representation sites. Changes in motor organization within and between hemispheres arise independently after stroke.

Stroke has been associated with many changes in motor system function, but there has been limited study of changes in somatotopic organization. This was examined in a group of patients with cortical stroke affecting primary sensorimotor cortex. In 17 patients with good outcome after cortical stroke involving precentral and/or postcentral gyri, plus 14 controls, four functional MRI evaluations of brain activity were obtained: finger, shoulder, and face motor tasks plus a sensory task, passive finger motion. For each, coordinates for contralateral primary sensorimotor cortex activation site were determined, as was a measure of inter-hemispheric balance. The normal motor somatotopy measured in controls was largely preserved after stroke. The main difference found between controls and patients was that the face was lateral to finger motor activation in all controls, but face was centered medial to finger in 43% of patients. Among patients, smaller infarct volume was associated with more ventral, and larger infarct with more dorsal, contralateral primary sensorimotor cortex activation. On the other hand, better behavioral outcome was associated with a more posterior, and poorer outcome with more anterior, activation. Larger infarct and poorer behavioral outcome were each associated with a change in inter-hemispheric balance towards the non-stroke hemisphere. Shifts in contralateral movement representation site did not correlate with changes in inter-hemispheric balance. Motor somatotopy is generally preserved after injury to primary sensorimotor cortex. Greater injury and larger behavioral deficits are associated with distinct effects on movement representation sites. Changes in motor organization within and between hemispheres arise independently after stroke.

Most therapies under development to restore motor function after spinal cord injury (SCI) assume intact brain motor functions. To examine this assumption, 12 patients with chronic, complete SCI and 12 controls underwent functional MRI during attempted, and during imagined, right foot movement, each at two force levels. In patients with SCI, many features of normal motor system function were preserved, however, several departures from normal were apparent: (i) volume of activation was generally much reduced, e.g. 4-8% of normal in primary sensorimotor cortex, in the setting of twice normal variance in signal change; (ii) abnormal activation patterns were present, e.g. increased pallido-thalamocortical loop activity during attempted movement and abnormal processing in primary sensorimotor cortex during imagined movement; and (iii) modulation of function with change in task or in force level did not conform to patterns seen in controls, e.g. in controls, attempted movement activated more than imagined movement did within left primary sensorimotor cortex and right dorsal cerebellum, while imagined movement activated more than attempted movement did in dorsolateral prefrontal cortex and right precentral gyrus. These modulations were absent in patients with SCI. Many features of brain motor system function during foot movement persist after chronic complete SCI. However, substantial derangements of brain activation, poor modulation of function with change in task demands and emergence of pathological brain events were present in patients. Because brain function is central to voluntary movement, interventions that aim to improve motor function after chronic SCI likely also need to attend to these abnormalities of brain function.

Most therapies under development to restore motor function after spinal cord injury (SCI) assume intact brain motor functions. To examine this assumption, 12 patients with chronic, complete SCI and 12 controls underwent functional MRI during attempted, and during imagined, right foot movement, each at two force levels. In patients with SCI, many features of normal motor system function were preserved, however, several departures from normal were apparent: (i) volume of activation was generally much reduced, e.g. 4-8% of normal in primary sensorimotor cortex, in the setting of twice normal variance in signal change; (ii) abnormal activation patterns were present, e.g. increased pallido-thalamocortical loop activity during attempted movement and abnormal processing in primary sensorimotor cortex during imagined movement; and (iii) modulation of function with change in task or in force level did not conform to patterns seen in controls, e.g. in controls, attempted movement activated more than imagined movement did within left primary sensorimotor cortex and right dorsal cerebellum, while imagined movement activated more than attempted movement did in dorsolateral prefrontal cortex and right precentral gyrus. These modulations were absent in patients with SCI. Many features of brain motor system function during foot movement persist after chronic complete SCI. However, substantial derangements of brain activation, poor modulation of function with change in task demands and emergence of pathological brain events were present in patients. Because brain function is central to voluntary movement, interventions that aim to improve motor function after chronic SCI likely also need to attend to these abnormalities of brain function.