Corticoreticulospinal tract neurophysiology in an arm and hand muscle in healthy and stroke subjects.

KEY POINTS: The corticoreticulospinal tract (CReST) is a descending motor pathway that reorganizes after corticospinal tract (CST) injury in animals. In humans, the pattern of CReST innervation to upper limb muscles has not been carefully examined in healthy individuals or individuals with CST injury. In the present study, we assessed CReST projections to an arm and hand muscle on the same side of the body in healthy and chronic stoke subjects using transcranial magnetic stimulation. We show that CReST connection strength to the muscles differs between healthy and stroke subjects, with stronger connections to the hand than arm in healthy subjects, and stronger connections to the arm than hand in stroke subjects. These results help us better understand CReST innervation patterns in the upper limb, and may point to its role in normal motor function and motor recovery in humans. ABSTRACT: The corticoreticulospinal tract (CReST) is a major descending motor pathway in many animals, but little is known about its innervation patterns in proximal and distal upper extremity muscles in humans. The contralesional CReST furthermore reorganizes after corticospinal tract (CST) injury in animals, but it is less clear whether CReST innervation changes after stroke in humans. We thus examined CReST functional connectivity, connection strength, and modulation in an arm and hand muscle of healthy (n = 15) and chronic stroke (n = 16) subjects. We delivered transcranial magnetic stimulation to the contralesional hemisphere (assigned in healthy subjects) to elicit ipsilateral motor evoked potentials (iMEPs) from the paretic biceps (BIC) and first dorsal interosseous (FDI) muscle. We operationalized CReST functional connectivity as iMEP presence/absence, CReST projection strength as iMEP size and CReST modulation as change in iMEP size by head rotation. We found comparable CReST functional connectivity to the BICs and FDIs in both subject groups. However, the pattern of CReST connection strength to the muscles diverged between groups, with stronger connections to FDIs than BICs in healthy subjects and stronger connections to BICs than FDIs in stroke subjects. Head rotation modulated only FDI iMEPs of healthy subjects. Our findings indicate that the healthy CReST does not have a proximal innervation bias, and its strong FDI connections may have functional relevance to finger individuation. The reversed CReST innervation pattern in stroke subjects confirms its reorganization after CST injury, and its strong BIC connections may indicate upregulation for particular upper extremity muscles or their functional actions.

When colours split from objects: The disconnection of colour perception from colour language and colour knowledge.

We investigated object-colour knowledge in RDS, a patient with impaired colour naming after a left occipito-temporal stroke. RDS's colour perception, object naming and verbal colour-knowledge (the ability to verbally say the typical colour of an object) were relatively spared. RDS was also able to state if an object was appropriately coloured or not. However, he could neither match colour names to coloured objects, nor match colour patches to grey-scale objects. Thus, RDS's colour-naming deficit was associated with an impaired ability to conceptually relate visually presented object shapes and colours. These results suggest that objects in their typical colour are processed holistically in the visual modality, and that abilities important for colour naming may also be involved in abstracting colours from visual objects. We discuss these findings in the context of developmental psychology and linguistic anthropology, and propose a model of neuro-functional organization of object-colour knowledge.

Corticospinal and corticoreticulospinal projections benefit motor behaviors in chronic stroke.

After corticospinal tract (CST) stroke, several motor deficits in the upper extremity (UE) emerge, including diminished muscle strength, motor control, and muscle individuation. Both the ipsilesional CST and contralesional corticoreticulospinal tract (CReST) innervate the paretic UE and may have different innervation patterns for the proximal and distal UE segments. These patterns may underpin distinct pathway relationships to separable motor behaviors. In this cross-sectional study of 15 chronic stroke patients and 28 healthy subjects, we examined two key questions: (1) whether segmental motor behaviors differentially relate to ipsilesional CST and contralesional CReST projection strengths, and (2) whether motor behaviors segmentally differ in the paretic UE. We measured strength, motor control, and muscle individuation in a proximal (biceps, BIC) and distal muscle (first dorsal interosseous, FDI) of the paretic UE. We measured the projection strengths of the ipsilesional CST and contralesional CReST to these muscles using transcranial magnetic stimulation (TMS). Stroke subjects had abnormal motor control and muscle individuation despite strength comparable to healthy subjects. In stroke subjects, stronger ipsilesional CST projections were linked to superior motor control in both UE segments, whereas stronger contralesional CReST projections were linked to superior muscle strength and individuation in both UE segments. Notably, both pathways also shared associations with behaviors in the proximal segment. Motor control deficits were segmentally comparable, but muscle individuation was worse for distal motor performance. These results suggest that each pathway has specialized contributions to chronic motor behaviors but also work together, with varying levels of success in supporting chronic deficits. Key points summary: Individuals with chronic stroke typically have deficits in strength, motor control, and muscle individuation in their paretic upper extremity (UE). It remains unclear how these altered behaviors relate to descending motor pathways and whether they differ by proximal and distal UE segment.In this study, we used transcranial magnetic stimulation (TMS) to examine projection strengths of the ipsilesional corticospinal tract (CST) and contralesional corticoreticulospinal tract (CReST) with respect to quantitated motor behaviors in chronic stroke.We found that stronger ipsilesional CST projections were associated with better motor control in both UE segments, whereas stronger contralesional CReST projections were associated with better strength and individuation in both UE segments. In addition, projections of both pathways shared associations with motor behaviors in the proximal UE segment.We also found that deficits in strength and motor control were comparable across UE segments, but muscle individuation was worse with controlled movement in the distal UE segment.These results suggest that the CST and CReST have specialized contributions to chronic motor behaviors and also work together, although with different degrees of efficacy.

The distribution of transcallosal inhibition to upper extremity muscles is altered in chronic stroke.

OBJECTIVE: To determine if the distribution of transcallosal inhibition (TI) acting on proximal and distal upper extremity muscles is altered in chronic stroke. METHODS: We examined thirteen healthy controls and sixteen mildly to moderately impaired chronic stroke patients. We used transcranial magnetic stimulation (TMS) to probe TI from the contralesional onto ipsilesional hemisphere (assigned in controls). We recorded the ipsilateral silent period in the paretic biceps (BIC) and first dorsal interosseous (FDI). We measured TI strength, distribution gradient (TI difference between muscles), and motor impairment (Fugl-Meyer Assessment). RESULTS: Both groups had stronger TI acting on their FDIs than BICs (p < 0.001). However, stroke patients also had stronger TI acting on their BICs than controls (p = 0.034), resulting in a flatter distribution of inhibition (p = 0.028). In patients, stronger FDI inhibition correlated with less hand impairment (p = 0.031); BIC inhibition was not correlated to impairment. CONCLUSION: TI is more evenly distributed to the paretic FDI and BIC in chronic stroke. The relative increase in proximal inhibition does not relate to better function, as it does distally. SIGNIFICANCE: The results expand our knowledge about segment-specific neurophysiology and its relevance to impairment after stroke.

Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis.

Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper-limb sensorimotor impairment. We investigated associations between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross-sectional T1-weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta-Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA-UE (Fugl-Meyer Assessment of Upper Extremity). Robust mixed-effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; ß=0.16) but not contralesional (P=0.96; ß=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; ß=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; ß=-0.26) and contralesional (P=0.006; ß=-0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; ß=-0.21) and extent of sensorimotor damage (P=0.003; ß=-0.15). Conclusions The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.

Motor adaptation and internal model formation in a robot-mediated forcefield.

Background: Motor adaptation relies on error-based learning for accurate movements in changing environments. However, the neurophysiological mechanisms driving individual differences in performance are unclear. Transcranial magnetic stimulation (TMS)-evoked potential can provide a direct measure of cortical excitability. Objective: To investigate cortical excitability as a predictor of motor learning and motor adaptation in a robot-mediated forcefield. Methods: A group of 15 right-handed healthy participants (mean age 23 years) performed a robot-mediated forcefield perturbation task. There were two conditions: unperturbed non-adaptation and perturbed adaptation. TMS was applied in the resting state at baseline and following motor adaptation over the contralateral primary motor cortex (left M1). Electroencephalographic (EEG) activity was continuously recorded, and cortical excitability was measured by TMS-evoked potential (TEP). Motor learning was quantified by the motor learning index. Results: Larger error-related negativity (ERN) in fronto-central regions was associated with improved motor performance as measured by a reduction in trajectory errors. Baseline TEP N100 peak amplitude predicted motor learning (P = 0.005), which was significantly attenuated relative to baseline (P = 0.0018) following motor adaptation. Conclusions: ERN reflected the formation of a predictive internal model adapted to the forcefield perturbation. Attenuation in TEP N100 amplitude reflected an increase in cortical excitability with motor adaptation reflecting neuroplastic changes in the sensorimotor cortex. TEP N100 is a potential biomarker for predicting the outcome in robot-mediated therapy and a mechanism to investigate psychomotor abnormalities in depression.

Color Categorization Independent of Color Naming.

Color is continuous, yet we group colors into discrete categories associated with color names (e.g., yellow, blue). Color categorization is a case in point in the debate on how language shapes human cognition. Evidence suggests that color categorization depends on top-down input from the language system to the visual cortex. We directly tested this hypothesis by assessing color categorization in a stroke patient, RDS, with a rare, selective deficit in naming visually presented chromatic colors, and relatively preserved achromatic color naming. Multimodal MRI revealed a left occipito-temporal lesion that directly damaged left color-biased regions, and functionally disconnected their right-hemisphere homologs from the language system. The lesion had a greater effect on RDS's chromatic color naming than on color categorization, which was relatively preserved on a nonverbal task. Color categorization and naming can thus be independent in the human brain, challenging the mandatory involvement of language in adult human cognition.

Muscle co-contraction patterns in robot-mediated force field learning to guide specific muscle group training.

BACKGROUND: Muscle co-contraction is a strategy of increasing movement accuracy and stability employed in dealing with force perturbation of movement. It is often seen in neuropathological populations. The direction of movement influences the pattern of co-contraction, but not all movements are easily achievable for populations with motor deficits. Manipulating the direction of the force instead, may be a promising rehabilitation protocol to train movement with use of a co-contraction reduction strategy. Force field learning paradigms provide a well described procedure to evoke and test muscle co-contraction. OBJECTIVE: The aim of this study was to test the muscle co-contraction pattern in a wide range of arm muscles in different force-field directions utilising a robot-mediated force field learning paradigm of motor adaptation. METHOD: Forty-two participants volunteered to participate in a study utilising robot-mediated force field motor adaptation paradigm with a clockwise or counter-clockwise force field. Kinematics and surface electromyography (EMG) of eight arm muscles were measured. RESULTS: Both muscle activation and co-contraction was earlier and stronger in flexors in the clockwise condition and in extensors in the counter-clockwise condition. CONCLUSIONS: Manipulating the force field direction leads to changes in the pattern of muscle co-contraction.