Causal Link between the Cortico-Rubral Pathway and Functional Recovery through Forced Impaired Limb Use in Rats with Stroke.

Intensive rehabilitation is believed to induce use-dependent plasticity in the injured nervous system; however, its causal relationship to functional recovery is unclear. Here, we performed systematic analysis of the effects of forced use of an impaired forelimb on the recovery of rats after lesioning the internal capsule with intracerebral hemorrhage (ICH). Forced limb use (FLU) group rats exhibited better recovery of skilled forelimb functions and their cortical motor area with forelimb representation was restored and enlarged on the ipsilesional side. In addition, abundant axonal sprouting from the reemerged forelimb area was found in the ipsilateral red nucleus after FLU. To test the causal relationship between the plasticity in the cortico-rubral pathway and recovery, loss-of-function experiments were conducted using a double-viral vector technique, which induces selective blockade of the target pathway. Blockade of the cortico-rubral tract resulted in deficits of the recovered forelimb function in FLU group rats. These findings suggest that the cortico-rubral pathway is a substrate for recovery induced by intensive rehabilitation after ICH. SIGNIFICANCE STATEMENT: The research aimed at determining the causal linkage between reorganization of the motor pathway induced by intensive rehabilitative training and recovery after stroke. We clarified the expansion of the forelimb representation area of the ipsilesional motor cortex by forced impaired forelimb use (FLU) after lesioning the internal capsule with intracerebral hemorrhaging (ICH) in rats. Anterograde tracing showed robust axonal sprouting from the forelimb area to the red nucleus in response to FLU. Selective blockade of the cortico-rubral pathway by the novel double-viral vector technique clearly revealed that the increased cortico-rubral axonal projections had causal linkage to the recovery of reaching movements induced by FLU. Our data demonstrate that the cortico-rubral pathway is responsible for the effect of intensive limb use.

Evaluation of White Matter Injury Patterns Underlying Neuropsychiatric Symptoms after Mild Traumatic Brain Injury.

PURPOSE: To determine if a central axonal injury underlies neuropsychiatric symptoms after mild traumatic brain injury (mTBI) by using tract-based spatial statistics analysis of diffusion-tensor images. MATERIALS AND METHODS: The institutional review board approved this study, with waiver of informed consent. Diffusion-tensor imaging and serial neurocognitive testing with the Immediate Post-Concussion Assessment and Cognitive Testing evaluation were performed in 45 patients with mTBI (38 with irritability, 32 with depression, and 18 with anxiety). Control subjects consisted of 29 patients with mTBI without neuropsychiatric symptoms. Fractional anisotropy and diffusivity maps were analyzed by using tract-based spatial statistics with a multivariate general linear model. Diffusion-tensor imaging findings were correlated with symptom severity, neurocognitive test scores, and time to recovery with the Pearson correlation coefficient. RESULTS: Compared with control subjects, patients with mTBI and depression had decreased fractional anisotropy in the superior longitudinal fasciculus (P = .006), white matter around the nucleus accumbens (P = .03), and anterior limb of the internal capsule (P = .02). Patients with anxiety had diminished fractional anisotropy in the vermis (P = .04). No regions of significantly decreased fractional anisotropy were seen in patients with irritability relative to control subjects. Injury in the region of the nucleus accumbens inversely correlated with recovery time in patients with depression (r = -0.480, P = .005). CONCLUSION: Unique white matter injury patterns were seen for two major posttraumatic neuropsychiatric symptoms. Injury to the cerebellar vermis in patients with mTBI and anxiety may indicate underlying dysfunction in primitive fear conditioning circuits in the cerebellum. Involvement of the nucleus accumbens in depression after mTBI may suggest an underlying dysfunctional reward circuit that affects the prognosis in these patients.

Effects of virtual reality therapy on upper limb function after stroke and the role of neuroimaging as a predictor of a better response.

OBJECTIVE: Virtual reality therapy (VRT) is an interactive intervention that induces neuroplasticity. The aim was to evaluate the effects of VRT associated with conventional rehabilitation for an upper limb after stroke, and the neuroimaging predictors of a better response to VRT. METHODS: Patients with stroke were selected, and clinical neurological, upper limb function, and quality of life were evaluated. Statistical analysis was performed using a linear model comparing pre- and post-VRT. Lesions were segmented in the post-stroke computed tomography. A voxel-based lesion-symptom mapping approach was used to investigate the relationship between the lesion and upper limb function. RESULTS: Eighteen patients were studied (55.5 ± 13.9 years of age). Quality of life, functional independence, and dexterity of the upper limb showed improvement after VRT (p < 0.001). Neuroimaging analysis showed negative correlations between the internal capsule lesion and functional recovery. CONCLUSION: VRT showed benefits for patients with stroke, but when there was an internal capsule lesion, a worse response was observed.

Hockey Concussion Education Project, Part 3. White matter microstructure in ice hockey players with a history of concussion: a diffusion tensor imaging study.

OBJECT: The aim of this study was to examine the brain's white matter microstructure by using MR diffusion tensor imaging (DTI) in ice hockey players with a history of clinically symptomatic concussion compared with players without a history of concussion. METHODS: Sixteen players with a history of concussion (concussed group; mean age 21.7 ± 1.5 years; 6 female) and 18 players without a history of concussion (nonconcussed group; mean age 21.3 ± 1.8 years, 10 female) underwent 3-T DTI at the end of the 2011-2012 Canadian Interuniversity Sports ice hockey season. Tract-based spatial statistics (TBSS) was used to test for group differences in fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and the measure "trace," or mean diffusivity. Cognitive evaluation was performed using the Immediate Postconcussion Assessment and Cognitive Test (ImPACT) and the Sport Concussion Assessment Tool-2 (SCAT2). RESULTS: TBSS revealed a significant increase in FA and AD, and a significant decrease in RD and trace in several brain regions in the concussed group, compared with the nonconcussed group (p < 0.05). The regions with increased FA and decreased RD and trace included the right posterior limb of the internal capsule, the right corona radiata, and the right temporal lobe. Increased AD was observed in a small area in the left corona radiata. The DTI measures correlated with neither the ImPACT nor the SCAT2 scores. CONCLUSIONS: The results of the current study indicate that a history of concussion may result in alterations of the brain's white matter microstructure in ice hockey players. Increased FA based on decreased RD may reflect neuroinflammatory or neuroplastic processes of the brain responding to brain trauma. Future studies are needed that include a longitudinal analysis of the brain's structure and function following a concussion to elucidate further the complex time course of DTI changes and their clinical meaning.

Effects of virtual reality therapy on upper limb function after stroke and the role of neuroimaging as a predictor of a better response / Efeitos da terapia de realidade virtual na função do membro superior após AVC e o papel da neuroimagem como preditor de melhor resposta

ABSTRACT Background: Virtual reality therapy (VRT) is an interactive intervention that induces neuroplasticity. The aim was to evaluate the effects of VRT associated with conventional rehabilitation for an upper limb after stroke, and the neuroimaging predictors of a better response to VRT. Methods: Patients with stroke were selected, and clinical neurological, upper limb function, and quality of life were evaluated. Statistical analysis was performed using a linear model comparing pre- and post-VRT. Lesions were segmented in the post-stroke computed tomography. A voxel-based lesion-symptom mapping approach was used to investigate the relationship between the lesion and upper limb function. Results: Eighteen patients were studied (55.5 ± 13.9 years of age). Quality of life, functional independence, and dexterity of the upper limb showed improvement after VRT (p < 0.001). Neuroimaging analysis showed negative correlations between the internal capsule lesion and functional recovery. Conclusion: VRT showed benefits for patients with stroke, but when there was an internal capsule lesion, a worse response was observed.

RESUMO Introdução: A realidade virtual (RV) é uma intervenção interativa que induz a neuroplasticidade. O objetivo deste estudo foi avaliar os efeitos da RV associado à reabilitação convencional na função do membro superior após o AVC e as características preditores de neuroimagem de melhor resposta a esta terapia. Métodos: os pacientes com AVC foram selecionados, e as características neurológicas, a função do membro superior e a qualidade de vida foram avaliadas. A análise estatística foi realizada por meio de modelo linear geral comparando resultados pré e pós-intervenção. As lesões foram segmentadas na tomografia computadorizada após o AVC. A abordagem de mapeamento da lesão-sintoma baseada em voxel foi utilizada para avaliar a relação entre a lesão e a função do membro superior. Resultados: Foram estudados 18 pacientes (8 mulheres, 55,5 ± 13,9 anos). A qualidade de vida, independência funcional, características funcionais e destreza do membro superior apresentaram melhora após RV (p < 0,001). A análise de imagem mostrou correlações negativas principalmente entre a cápsula interna e a recuperação funcional do membro superior. Conclusão: A RV mostrou benefícios para pacientes com AVC, mas quando houve lesão da cápsula interna apresentaram pior resposta à terapia.

Diffusion tensor imaging of mild to moderate blast-related traumatic brain injury and its sequelae.

To evaluate the effects of mild to moderate blast-related traumatic brain injury (TBI) on the microstructure of brain white matter (WM) and neurobehavioral outcomes, we studied 37 veterans and service members (mean age 31.5 years, SD = 7.2; post-injury interval 871.5 days; SD = 343.1), whose report of acute neurological status was consistent with sustaining mild to moderate TBI due to blast while serving in Iraq or Afghanistan. Fifteen veterans without a history of TBI or exposure to blast (mean age 31.4 years, SD = 5.4) served as a comparison group, including seven subjects with extracranial injury (post-injury interval 919.5 days, SD = 455.1), and eight who were uninjured. Magnetic resonance imaging disclosed focal lesions in five TBI participants. Post-concussion symptoms (Neurobehavioral Symptom Inventory), post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist-Civilian), and global distress and depression (Brief Symptom Inventory) were worse in the TBI participants than the comparison group, but no group differences were found in perceived physical or mental functioning (SF-12). Verbal memory (Selective Reminding) was less efficient in the TBI group, but there were no group differences in nonverbal memory (Selective Reminding) or decision making (Iowa Gambling Task). Verbal memory in the TBI group was unrelated to PTSD severity. Diffusion tensor imaging (DTI) using tractography, standard single-slice region-of-interest measurement, and voxel-based analysis disclosed no group differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC). However, FA of the left and right posterior internal capsule and left corticospinal tract was positively correlated with total words consistently recalled, whereas ADC for the left and right uncinate fasciculi and left posterior internal capsule was negatively correlated with this measure of verbal memory. Correlations of DTI variables with symptom measures were non-significant and inconsistent. Our data do not show WM injury in mild to moderate blast-related TBI in veterans despite their residual symptoms and difficulty in verbal memory. Limitations of the study and implications for future research are also discussed.

Basal ganglia and internal capsule stroke in childhood--risk factors, neuroimaging, and outcome in a series of 28 patients: a tertiary hospital experience.

We present 28 patients with basal ganglia ischemic stroke and describe the main neurological manifestations, neuroimaging findings, risk factors, and outcome. In 23 cases, at least 1 risk factor was identified. A total of 7 cases (25%) had antecedent of varicella infection and 7 cases (25%) had preceding mild head trauma. Similar antecedents were present only in 2.6% and 5.3% of patients with nonbasal ganglia stroke, respectively (odds ratio: 12.2, 95% confidence interval: 2.04-124.65 and odds ratio: 5.92, 95% confidence interval: 1.32-29.7). The arterial abnormalities identified in 10 patients were narrowing (6) or occlusion (4) of the M1 segment. After a median follow-up of 24 months, 19 patients had a good outcome. Magnetic resonance angiography and catheter cerebral angiography played an important role in the identification of arterial disease. We propose that basal ganglia infarction is a different group of ischemic stroke with prevalent risk factors (varicella infection and mild head trauma) and good outcome.

Lacunar infarct during pallidotomy: case report.

A symptomatic lacunar infarct is an unusual complication which may develop during stereotactically guided pallidotomy using radiofrequency thermoablation. We describe a 54-year-old man with Parkinson's disease involving predominantly the right side, progressively deteriorating under medical management. He underwent stereotactically guided radiofrequency thermoablation of the posteroventral globus pallidus interna. Despite intraoperative microelectrode recording and stimulation, the patient developed right facial weakness and pronator drift during the procedure. MRI showed a small lacunar infarct in the left internal capsule, in addition to the appropriately placed ablative lesion. We discuss the potential mechanisms for this type of injury.

Reorganization of speech production at the motor cortex and cerebellum following capsular infarction: a follow-up functional magnetic resonance imaging study.

Based on clinical data, Geschwind assumed left hemisphere dominance of speech production to extend to the cortical representation of articulatory and phonatory functions at the motor cortex. This author suggested, furthermore, that the clinical observation of rapid recovery from articulatory impairments after damage to the left-sided corticobulbar tracts reflects compensatory activation of an alternative pathway involving the contralateral pre-central gyrus and its efferent projections. In order to test this hypothesis, functional magnetic resonance imaging (fMRI) was performed 4 and 35 days after stroke in a 38-year-old man who had experienced sudden speech deterioration ('dysarthric speech') concomitant with weakness of the right upper limb and the right side of the face. Computerized tomography demonstrated an ischaemic infarction within the left internal capsule. The patient fully recovered from dysarthria within 9 days. Activation of the right hemisphere analogues of Broca and Wernicke areas has been assumed to contribute to recovery from aphasia. As a further aspect of the reorganization of speech function, the present case study demonstrates for the first time by means of fMRI a selective 'shift' of the cortical representation of speech motor control to the right Rolandic cortex and the left cerebellum during restitution of articulation in a case of transient dysarthria following infarction of the left internal capsule.