BackgroundThe neurobiology underlying ASD is largely unknown but altered neural excitability/inhi... more BackgroundThe neurobiology underlying ASD is largely unknown but altered neural excitability/inhibitory ratios have been reported. Memantine is an N-methyl-D-aspartate (NMDA) glutamatergic antagonist studied for the treatment of core ASD symptoms, with mixed results. We examined whether glutamatergic levels were associated with and predicted response to memantine in an exploratory pilot study.MethodsTen adult participants with ASD underwent proton magnetic resonance spectroscopy (1H-MRS) imaging at baseline and behavioral assessments before and after 12-weeks of open-label memantine. Post-treatment scores on Clinical Global Impressions–Improvement (CGI-I) for social interaction were the primary outcome measure, and scores on the Social Responsiveness Scale (SRS) were included as a secondary outcome. LCModel was used to quantify the concentrations of Point RESolved Spectroscopy-detected glutamate+glutamine (Glx) (and other neurometabolites, i.e., N-acetylaspartate, NAA; creatine+phos...
2020 IEEE International Conference on Bioinformatics and Biomedicine (BIBM), 2020
Objectives: Stroke unleashes a complex series of repair-related neural events that leads to acute... more Objectives: Stroke unleashes a complex series of repair-related neural events that leads to acute functional impairment and, over a longer time-frame, results in the specific functional outcome for individual patients. A major repair-related mechanism is the decrease in tonic $\gamma-$aminobutyric acid (GABA) mediated inhibition. On a physiological level, a reduction of tonic inhibition (or disinhibition) within the motor system for example, augments plastic properties of the neural circuits resulting in creation of newly available networks and strengthening the existing ones, all to generate a motor output to the impaired arm. Our current knowledge derives largely from animal models, mainly rodents. Invivo evaluation of the nature of this type of inhibition in stroke patients is lacking; it remains difficult to discern whether such changes are functionally relevant in humans. Design: We assessed tonic GABAergic inhibition, using noninvasive MR Spectroscopy (MEGA-sLASER, 3T Siemens) measurements of GABA levels (a validated index of such inhibition in living human brain), in 3 subcortical stroke patients (66.3 [10.1] (mean [SD]) years old, 2 males, mildly impaired, NIHSS=6 for all; 22.2 [2.0] days after stroke onset). We selected the subacute phase of stroke to capture the profound changes of tonic GABAergic inhibition, as established in animal models. We selected patients with subcortical stroke to assess this mechanism in spared, viable cortices. We focused on 2 motor areas that play a major role in arm motor recovery after stroke, primary motor (M1) and premotor (PM) cortices. Note that patient’s recruitment has been stopped during the study due to COVID-19 pandemic. The stability of GABA measurements in these 2 areas was tested in 3 healthy controls (24.7 [4.0] yrs old, 2 women, both in the follicular phase of the menstrual cycle) at 23.7 [0.6] h interval. MEGA□sLASER parameters, processing, analysis, and voxel positioning were the same for both time points. The coefficient of variation (CoV = SD/mean of test-retest) was calculated for each area. Results: Relative to matched controls, we found a trend toward higher GABA levels in all areas (left M1 in control vs. M1 in injured hemisphere, ipsilesional, in stroke: $2.0 \pm 0.2$ vs $2.2 \pm 0.2, \mathrm{p}=0.2$, a 10% increase; left PM vs. ipsilesional PM: 1.9 [0.1] vs. 2.3 [0.2], p=0.08, 21% increase; right M1 vs. contralesional M1: 2.0 [0.5] vs. 2.2 [0.3], p=0.6, 10% increase; right PM vs. contralesional PM, 1.9 [0.2] vs. 2.2 [0.3], p=0.2, 16% increase). The differences in M1 GABA levels reported in patients compared with controls felt out (higher) of the range of normal GABA variability in the human brain (coefficient of variance, left M1, CoV 2.5-7.1%; right M1, 6.2-8.7%) while those in PM felt within this range (left PM, 11.1-20.4%; right PM, 15.724.3%). Due to the small sample size, the relationships between GABA levels and hand impairment were not assessed. Conclusions: Our preliminary data have shown there is a trend toward increased tonic GABAergic inhibition in motor areas, primarily in M1, early after stroke. If this trend is further demonstrated in larger sample size, this knowledge will provide evidence whether such mechanism is a robust biological substrate to drive functional improvements early after stroke.
Intramedullary spinal cord (SC) tumors are relatively rare tumors, accounting for only 2% to 4% o... more Intramedullary spinal cord (SC) tumors are relatively rare tumors, accounting for only 2% to 4% ofcentral nervous
ABSTRACT Background: Although strong experimental neurobehavioral evidences suggest that intensiv... more ABSTRACT Background: Although strong experimental neurobehavioral evidences suggest that intensive motor training improves recovery after stroke, we still have only limited knowledge whether similar neural mechanisms underlie both relearning during rehabilitation and de novo motor learning. It is also unclear whether improvement results from adaptive reorganization or behavioral compensation. In this study, we investigated cortical motor reorganization during an arm-focused motor training in stroke patients and age-sex matched healthy controls. We also studied whether learning-related motor network changes in patients were related to recovery of premorbid movement pattern. Methods: Eleven survivors of a first ischemic stroke located outside cortical motor areas (confirmed by T2-weighted MRI) and twelve controls underwent functional MRI, kinematic, and clinical (in patients) testing prior to and immediately after motor training. Participants were scanned performing a dynamic isometric handgrip task with the dominant (impaired) hand. Percentage signal changes of blood oxygen level-dependent (BOLD) signal were determined in hand representation areas in primary (M1), dorsal premotor, and supplementary motor areas. Kinematic assessment of elbow extension during a reach-to-grasp task and clinical measure of arm motor impairment (Fugl-Meyer Upper Extremity, FMUE, test) were administrated. Training consisted in a repetitive variable practice of a reach-to-grasp task with the impaired arm during a four-week period (12 days, 90 repetitions/day). BOLD and motor outcome differences as well as their relationships were evaluated. Results: After training, in controls, we found significant increased activation of the motor areas contralateral to the trained arm along with significant increased elbow extension. In patients, increased contralateral activation was associated with decreased ipsilateral activation (significantly in M1). Patients significantly increased elbow extension and improved clinical scores. The correlations between motor activation and elbow extension were similar with those in controls. Significant negative correlation was also found between ipsilateral M1 activation and FMUE. Conclusions: Our preliminary results suggest that learning-related brain and behavioral changes in stroke were somehow similar with those in controls. Further studies investigating training-induced changes in other brain regions as well as on the time course of these changes may help us to better clarify whether principles of motor relearning after stroke are similar with those of motor learning in an uninjured brain.
ABSTRACT Background Stroke is the leading cause of disability in the United States. This disabili... more ABSTRACT Background Stroke is the leading cause of disability in the United States. This disability could be reduced by restorative therapies. The ability to predict response to restorative therapies would improve patient selection, which would optimize treatment efficacy. Despite vast research on this subject, it is unclear which predictor, or group of predictors, has greatest predictive value. Since motor recovery appears to be influenced by residual function, we proposed here that the extent of cellular injury in spared primary motor cortices (M1) provides valuable prognostic information of recovery. Specifically, we hypothesized that patients with less dysfunctional M1s would have a better chance of recovery, having reserve to boost either cortical activity or behavioral output in response to arm use. We also hypothesized that M1 measures provide insights into biological mechanisms underlying recovery when metrics of stroke severity do not, and combined with these metrics predict recovery better than M1 measures alone. Methods Chronic survivors (n=10, 8 males, age 58.7±6.8 years, 32.9±37.7 months post-onset) of an ischemic subcortical stroke leading to arm motor impairment (Fugl-Meyer test, FMPRE, 35.6±18.6) underwent proton magnetic resonance spectroscopic (1H-MRS) and structural MRI evaluations prior to a motor training (PRE). Motor training consisted in repetition of a reach-to-grasp task with the impaired arm for a 12-day acquisition phase spaced over four weeks (90 repetitions/day, 3 days/week). Neurochemicals related to neurons, glia, and the neuronal-glial neurotransmitter system were measured in the hand representation in M1s. Lesion volume (LV) was quantified. FM was also administrated after intervention (POST) and motor recovery was defined as change in FM scores over training (ΔFM). Results PRE: There were no correlations between FMPRE or LV and M1 measures. POST: We observed training-related improvements in FM score with ΔFM=3.9±2.4. We found evidence that individual or composite measure of ipsilesional neurochemicals predicts the extent of the training-related improvements and their predictive value was stronger than that of FMPRE or LV. By contrast, we failed to detect significant correlations between ΔFM and FMPRE or LV. The correlations between M1 measures and ΔFM were greatly strengthened by adding FMPRE and/or LV, especially for the contralesional M1. These combinations also predicted ΔFM more accurately than did FMPRE, LV or 1H-MRS alone. Conclusions We have shown that even in a moderate size sample the M1 neurochemical profile predicts the potential to recover with an intervention, beyond that provided by conventional indices of stroke severity, and combined with these indices improved prediction value. Such a prognostic tool of motor recovery may help clinicians to prescribe restorative therapies with maximal efficacy, by matching treatment with patients who have a sufficient biological target. Since automated 1H-MRS is increasingly available on clinical scanners, a 1H-MRS-based biomarker is feasible in routine practice.
International journal of physical medicine & rehabilitation, 2016
We investigated the effects of an intensive impairment-oriented training on neuronal state (asses... more We investigated the effects of an intensive impairment-oriented training on neuronal state (assessed by proton MR spectroscopy, 1H-MRS) of the spared motor and premotor cortices in the injured (ipsilesional) hemisphere and clinical impairment in a patient with chronic subcortical stroke. One survivor of a single ischemic stroke located outside of the motor and premotor cortices (assessed on T1-weighted MRI) was studied at six months after stroke. We used functional MRI-guided 1H-MRS to quantify the levels of N-acetylaspartate (NAA - a putative neuronal marker) in the hand representation within ipsilesional primary motor cortex (M1), dorsal premotor cortex (dPM) and supplementary motor area (SMA), and Fugl-Meyer (normal=66 points) test to assess the arm motor impairment immediately before and after a motor training paradigm. Training comprised intensive variable practice (1080 repetitions over 12 day-period) of a reach-to-grasp task with the impaired hand while focusing the learner&#...
Reductions in sensory and motor activity following unilateral upper limb amputation during adulth... more Reductions in sensory and motor activity following unilateral upper limb amputation during adulthood are associated with widespread, activity-dependent reorganization of the gray matter and white matter through the central nervous system. Likewise, in cases of congenital limb absence there is evidence that limited afferent or efferent activity affects the structural integrity of white matter pathways serving the affected side. Evidence that the structural integrity of mature sensory and motor tracts controlling the lost upper limb exhibits similar activity dependence is, however, sparse and inconsistent. Here we used diffusion tensor tractography to test whether amputation of the dominant right hand during adulthood ( n = 16) alters the microstructural integrity of the major sensory (medial lemniscus, ML) and motor (corticospinal tract, CST) pathways controlling missing hand function. Consistent with prior findings, healthy control subjects ( n = 27) exhibited higher fractional anis...
Participants: Adults with chronic, troublesome sialorrhea due to Parkinson’s disease, stroke, and... more Participants: Adults with chronic, troublesome sialorrhea due to Parkinson’s disease, stroke, and other etiologies. Interventions: Subjects received placebo, 75U or 100U incobotulinumtoxinA in the first treatment cycle (MP) and either 75U or 100U incobotulinumtoxinA in each of 3 further treatment cycles in the EP. Main Outcome Measures: Unstimulated Salivary Flow Rate (uSFR); Global Impression of Change Scale (GICS), Drooling Severity and Frequency Scale (DSFS); modified Radboud Oral Motor Inventory in Parkinson’s Disease (mROMP) drooling. Adverse events were monitored throughout. Results: Subjects who received incobotulinumtoxinA throughout the MP and EP demonstrated sustained improvements in uSFR across treatment cycles. In the 75U group, mean uSFR (g/min) was 0.42 at study baseline (n1⁄474) and 0.36 (n1⁄468), 0.28, 0.23, and 0.23 at respective week 4 follow-ups after injections 1 to 4. Response was numerically greater in the 100U group (n1⁄474): 0.40 at study baseline and 0.27 (n1⁄472), 0.22, 0.21, and 0.17 at week 4 follow-ups after consecutive injections. Mean subject GICS scores indicated sustained improvement in both treatment groups. Similar trends of improvement were also observed for the DSFS and mROMP analyses. In the small group of subjects (n1⁄432), who switched from placebo in the MP to incobotulinumtoxinA in the EP, treatment benefit was also shown. Consistent with the MP, safety and tolerability were favorable in the EP, with no new/unexpected findings. Conclusions: Repeated treatment with incobotulinumtoxinA is safe and effective for sustained improvement in sialorrhea. Level of Evidence: Level I
Journal of autism and developmental disorders, Jan 23, 2018
Atypical functional connectivity (FC) and an imbalance of excitation-to-inhibition (E/I) have bee... more Atypical functional connectivity (FC) and an imbalance of excitation-to-inhibition (E/I) have been previously reported in cerebro-cerebellar circuits in autism spectrum disorder (ASD). The current investigation used resting state fMRI and proton magnetic resonance spectroscopy (H-MRS) to examine the relationships between E/I (glutamate + glutamine/GABA) and FC of the dorsolateral prefrontal cortex and posterolateral cerebellar hemisphere from 14 adolescents/adults with ASD and 12 age/sex/IQ-matched controls. In this pilot sample, cerebro-cerebellar FC was positively associated with cerebellar E/I and listening comprehension abilities in individuals with ASD but not controls. Additionally, a subgroup of individuals with ASD and low FC (n = 5) exhibited reduced E/I and impaired listening comprehension. Thus, altered functional coherence of cerebro-cerebellar circuits in ASD may be related with a cerebellar E/I imbalance.
American Journal of Physical Medicine & Rehabilitation
The aim of the study was to examine whether neural state of spared motor and premotor cortices ca... more The aim of the study was to examine whether neural state of spared motor and premotor cortices captured before a therapy predicts therapy-related motor gains in chronic subcortical stroke. Ten survivors, presenting chronic moderate upper limb impairment, underwent proton magnetic resonance spectroscopy, magnetic resonance imaging, clinical, and kinematics assessments before a 4-wk impairment-oriented training. Clinical/kinematics assessments were repeated after therapy, and motor gain was defined as positive values of clinical upper limb/elbow motion changes and negative values of trunk motion changes. Candidate predictors were N-acetylaspartate-neuronal marker, glutamate-glutamine-indicator of glutamatergic neurotransmission, and myo-inositol-glial marker, measured bilaterally within the upper limb territory in motor and premotor (premotor cortex, supplementary motor area) cortices. Traditional predictors (age, stroke length, pre-therapy upper limb clinical impairment, infarct volume) were also investigated. Poor motor gain was associated with lower glutamate-glutamine levels in ipsilesional primary motor cortex and premotor cortex (r = 0.77, P = 0.01 and r = 0.78, P = 0.008, respectively), lower N-acetylaspartate in ipsilesional premotor cortex (r = 0.69, P = 0.02), higher glutamate-glutamine in contralesional primary motor cortex (r = -0.68, P = 0.03), and lower glutamate-glutamine in contralesional supplementary motor area (r = 0.64, P = 0.04). These predictors outperformed myo-inositol metrics and traditional predictors (P ≈ 0.05-1.0). Glutamatergic state of bilateral motor and premotor cortices and neuronal state of ipsilesional premotor cortex may be important for predicting motor outcome in the context of a restorative therapy.
BackgroundThe neurobiology underlying ASD is largely unknown but altered neural excitability/inhi... more BackgroundThe neurobiology underlying ASD is largely unknown but altered neural excitability/inhibitory ratios have been reported. Memantine is an N-methyl-D-aspartate (NMDA) glutamatergic antagonist studied for the treatment of core ASD symptoms, with mixed results. We examined whether glutamatergic levels were associated with and predicted response to memantine in an exploratory pilot study.MethodsTen adult participants with ASD underwent proton magnetic resonance spectroscopy (1H-MRS) imaging at baseline and behavioral assessments before and after 12-weeks of open-label memantine. Post-treatment scores on Clinical Global Impressions–Improvement (CGI-I) for social interaction were the primary outcome measure, and scores on the Social Responsiveness Scale (SRS) were included as a secondary outcome. LCModel was used to quantify the concentrations of Point RESolved Spectroscopy-detected glutamate+glutamine (Glx) (and other neurometabolites, i.e., N-acetylaspartate, NAA; creatine+phos...
2020 IEEE International Conference on Bioinformatics and Biomedicine (BIBM), 2020
Objectives: Stroke unleashes a complex series of repair-related neural events that leads to acute... more Objectives: Stroke unleashes a complex series of repair-related neural events that leads to acute functional impairment and, over a longer time-frame, results in the specific functional outcome for individual patients. A major repair-related mechanism is the decrease in tonic $\gamma-$aminobutyric acid (GABA) mediated inhibition. On a physiological level, a reduction of tonic inhibition (or disinhibition) within the motor system for example, augments plastic properties of the neural circuits resulting in creation of newly available networks and strengthening the existing ones, all to generate a motor output to the impaired arm. Our current knowledge derives largely from animal models, mainly rodents. Invivo evaluation of the nature of this type of inhibition in stroke patients is lacking; it remains difficult to discern whether such changes are functionally relevant in humans. Design: We assessed tonic GABAergic inhibition, using noninvasive MR Spectroscopy (MEGA-sLASER, 3T Siemens) measurements of GABA levels (a validated index of such inhibition in living human brain), in 3 subcortical stroke patients (66.3 [10.1] (mean [SD]) years old, 2 males, mildly impaired, NIHSS=6 for all; 22.2 [2.0] days after stroke onset). We selected the subacute phase of stroke to capture the profound changes of tonic GABAergic inhibition, as established in animal models. We selected patients with subcortical stroke to assess this mechanism in spared, viable cortices. We focused on 2 motor areas that play a major role in arm motor recovery after stroke, primary motor (M1) and premotor (PM) cortices. Note that patient’s recruitment has been stopped during the study due to COVID-19 pandemic. The stability of GABA measurements in these 2 areas was tested in 3 healthy controls (24.7 [4.0] yrs old, 2 women, both in the follicular phase of the menstrual cycle) at 23.7 [0.6] h interval. MEGA□sLASER parameters, processing, analysis, and voxel positioning were the same for both time points. The coefficient of variation (CoV = SD/mean of test-retest) was calculated for each area. Results: Relative to matched controls, we found a trend toward higher GABA levels in all areas (left M1 in control vs. M1 in injured hemisphere, ipsilesional, in stroke: $2.0 \pm 0.2$ vs $2.2 \pm 0.2, \mathrm{p}=0.2$, a 10% increase; left PM vs. ipsilesional PM: 1.9 [0.1] vs. 2.3 [0.2], p=0.08, 21% increase; right M1 vs. contralesional M1: 2.0 [0.5] vs. 2.2 [0.3], p=0.6, 10% increase; right PM vs. contralesional PM, 1.9 [0.2] vs. 2.2 [0.3], p=0.2, 16% increase). The differences in M1 GABA levels reported in patients compared with controls felt out (higher) of the range of normal GABA variability in the human brain (coefficient of variance, left M1, CoV 2.5-7.1%; right M1, 6.2-8.7%) while those in PM felt within this range (left PM, 11.1-20.4%; right PM, 15.724.3%). Due to the small sample size, the relationships between GABA levels and hand impairment were not assessed. Conclusions: Our preliminary data have shown there is a trend toward increased tonic GABAergic inhibition in motor areas, primarily in M1, early after stroke. If this trend is further demonstrated in larger sample size, this knowledge will provide evidence whether such mechanism is a robust biological substrate to drive functional improvements early after stroke.
Intramedullary spinal cord (SC) tumors are relatively rare tumors, accounting for only 2% to 4% o... more Intramedullary spinal cord (SC) tumors are relatively rare tumors, accounting for only 2% to 4% ofcentral nervous
ABSTRACT Background: Although strong experimental neurobehavioral evidences suggest that intensiv... more ABSTRACT Background: Although strong experimental neurobehavioral evidences suggest that intensive motor training improves recovery after stroke, we still have only limited knowledge whether similar neural mechanisms underlie both relearning during rehabilitation and de novo motor learning. It is also unclear whether improvement results from adaptive reorganization or behavioral compensation. In this study, we investigated cortical motor reorganization during an arm-focused motor training in stroke patients and age-sex matched healthy controls. We also studied whether learning-related motor network changes in patients were related to recovery of premorbid movement pattern. Methods: Eleven survivors of a first ischemic stroke located outside cortical motor areas (confirmed by T2-weighted MRI) and twelve controls underwent functional MRI, kinematic, and clinical (in patients) testing prior to and immediately after motor training. Participants were scanned performing a dynamic isometric handgrip task with the dominant (impaired) hand. Percentage signal changes of blood oxygen level-dependent (BOLD) signal were determined in hand representation areas in primary (M1), dorsal premotor, and supplementary motor areas. Kinematic assessment of elbow extension during a reach-to-grasp task and clinical measure of arm motor impairment (Fugl-Meyer Upper Extremity, FMUE, test) were administrated. Training consisted in a repetitive variable practice of a reach-to-grasp task with the impaired arm during a four-week period (12 days, 90 repetitions/day). BOLD and motor outcome differences as well as their relationships were evaluated. Results: After training, in controls, we found significant increased activation of the motor areas contralateral to the trained arm along with significant increased elbow extension. In patients, increased contralateral activation was associated with decreased ipsilateral activation (significantly in M1). Patients significantly increased elbow extension and improved clinical scores. The correlations between motor activation and elbow extension were similar with those in controls. Significant negative correlation was also found between ipsilateral M1 activation and FMUE. Conclusions: Our preliminary results suggest that learning-related brain and behavioral changes in stroke were somehow similar with those in controls. Further studies investigating training-induced changes in other brain regions as well as on the time course of these changes may help us to better clarify whether principles of motor relearning after stroke are similar with those of motor learning in an uninjured brain.
ABSTRACT Background Stroke is the leading cause of disability in the United States. This disabili... more ABSTRACT Background Stroke is the leading cause of disability in the United States. This disability could be reduced by restorative therapies. The ability to predict response to restorative therapies would improve patient selection, which would optimize treatment efficacy. Despite vast research on this subject, it is unclear which predictor, or group of predictors, has greatest predictive value. Since motor recovery appears to be influenced by residual function, we proposed here that the extent of cellular injury in spared primary motor cortices (M1) provides valuable prognostic information of recovery. Specifically, we hypothesized that patients with less dysfunctional M1s would have a better chance of recovery, having reserve to boost either cortical activity or behavioral output in response to arm use. We also hypothesized that M1 measures provide insights into biological mechanisms underlying recovery when metrics of stroke severity do not, and combined with these metrics predict recovery better than M1 measures alone. Methods Chronic survivors (n=10, 8 males, age 58.7±6.8 years, 32.9±37.7 months post-onset) of an ischemic subcortical stroke leading to arm motor impairment (Fugl-Meyer test, FMPRE, 35.6±18.6) underwent proton magnetic resonance spectroscopic (1H-MRS) and structural MRI evaluations prior to a motor training (PRE). Motor training consisted in repetition of a reach-to-grasp task with the impaired arm for a 12-day acquisition phase spaced over four weeks (90 repetitions/day, 3 days/week). Neurochemicals related to neurons, glia, and the neuronal-glial neurotransmitter system were measured in the hand representation in M1s. Lesion volume (LV) was quantified. FM was also administrated after intervention (POST) and motor recovery was defined as change in FM scores over training (ΔFM). Results PRE: There were no correlations between FMPRE or LV and M1 measures. POST: We observed training-related improvements in FM score with ΔFM=3.9±2.4. We found evidence that individual or composite measure of ipsilesional neurochemicals predicts the extent of the training-related improvements and their predictive value was stronger than that of FMPRE or LV. By contrast, we failed to detect significant correlations between ΔFM and FMPRE or LV. The correlations between M1 measures and ΔFM were greatly strengthened by adding FMPRE and/or LV, especially for the contralesional M1. These combinations also predicted ΔFM more accurately than did FMPRE, LV or 1H-MRS alone. Conclusions We have shown that even in a moderate size sample the M1 neurochemical profile predicts the potential to recover with an intervention, beyond that provided by conventional indices of stroke severity, and combined with these indices improved prediction value. Such a prognostic tool of motor recovery may help clinicians to prescribe restorative therapies with maximal efficacy, by matching treatment with patients who have a sufficient biological target. Since automated 1H-MRS is increasingly available on clinical scanners, a 1H-MRS-based biomarker is feasible in routine practice.
International journal of physical medicine & rehabilitation, 2016
We investigated the effects of an intensive impairment-oriented training on neuronal state (asses... more We investigated the effects of an intensive impairment-oriented training on neuronal state (assessed by proton MR spectroscopy, 1H-MRS) of the spared motor and premotor cortices in the injured (ipsilesional) hemisphere and clinical impairment in a patient with chronic subcortical stroke. One survivor of a single ischemic stroke located outside of the motor and premotor cortices (assessed on T1-weighted MRI) was studied at six months after stroke. We used functional MRI-guided 1H-MRS to quantify the levels of N-acetylaspartate (NAA - a putative neuronal marker) in the hand representation within ipsilesional primary motor cortex (M1), dorsal premotor cortex (dPM) and supplementary motor area (SMA), and Fugl-Meyer (normal=66 points) test to assess the arm motor impairment immediately before and after a motor training paradigm. Training comprised intensive variable practice (1080 repetitions over 12 day-period) of a reach-to-grasp task with the impaired hand while focusing the learner&#...
Reductions in sensory and motor activity following unilateral upper limb amputation during adulth... more Reductions in sensory and motor activity following unilateral upper limb amputation during adulthood are associated with widespread, activity-dependent reorganization of the gray matter and white matter through the central nervous system. Likewise, in cases of congenital limb absence there is evidence that limited afferent or efferent activity affects the structural integrity of white matter pathways serving the affected side. Evidence that the structural integrity of mature sensory and motor tracts controlling the lost upper limb exhibits similar activity dependence is, however, sparse and inconsistent. Here we used diffusion tensor tractography to test whether amputation of the dominant right hand during adulthood ( n = 16) alters the microstructural integrity of the major sensory (medial lemniscus, ML) and motor (corticospinal tract, CST) pathways controlling missing hand function. Consistent with prior findings, healthy control subjects ( n = 27) exhibited higher fractional anis...
Participants: Adults with chronic, troublesome sialorrhea due to Parkinson’s disease, stroke, and... more Participants: Adults with chronic, troublesome sialorrhea due to Parkinson’s disease, stroke, and other etiologies. Interventions: Subjects received placebo, 75U or 100U incobotulinumtoxinA in the first treatment cycle (MP) and either 75U or 100U incobotulinumtoxinA in each of 3 further treatment cycles in the EP. Main Outcome Measures: Unstimulated Salivary Flow Rate (uSFR); Global Impression of Change Scale (GICS), Drooling Severity and Frequency Scale (DSFS); modified Radboud Oral Motor Inventory in Parkinson’s Disease (mROMP) drooling. Adverse events were monitored throughout. Results: Subjects who received incobotulinumtoxinA throughout the MP and EP demonstrated sustained improvements in uSFR across treatment cycles. In the 75U group, mean uSFR (g/min) was 0.42 at study baseline (n1⁄474) and 0.36 (n1⁄468), 0.28, 0.23, and 0.23 at respective week 4 follow-ups after injections 1 to 4. Response was numerically greater in the 100U group (n1⁄474): 0.40 at study baseline and 0.27 (n1⁄472), 0.22, 0.21, and 0.17 at week 4 follow-ups after consecutive injections. Mean subject GICS scores indicated sustained improvement in both treatment groups. Similar trends of improvement were also observed for the DSFS and mROMP analyses. In the small group of subjects (n1⁄432), who switched from placebo in the MP to incobotulinumtoxinA in the EP, treatment benefit was also shown. Consistent with the MP, safety and tolerability were favorable in the EP, with no new/unexpected findings. Conclusions: Repeated treatment with incobotulinumtoxinA is safe and effective for sustained improvement in sialorrhea. Level of Evidence: Level I
Journal of autism and developmental disorders, Jan 23, 2018
Atypical functional connectivity (FC) and an imbalance of excitation-to-inhibition (E/I) have bee... more Atypical functional connectivity (FC) and an imbalance of excitation-to-inhibition (E/I) have been previously reported in cerebro-cerebellar circuits in autism spectrum disorder (ASD). The current investigation used resting state fMRI and proton magnetic resonance spectroscopy (H-MRS) to examine the relationships between E/I (glutamate + glutamine/GABA) and FC of the dorsolateral prefrontal cortex and posterolateral cerebellar hemisphere from 14 adolescents/adults with ASD and 12 age/sex/IQ-matched controls. In this pilot sample, cerebro-cerebellar FC was positively associated with cerebellar E/I and listening comprehension abilities in individuals with ASD but not controls. Additionally, a subgroup of individuals with ASD and low FC (n = 5) exhibited reduced E/I and impaired listening comprehension. Thus, altered functional coherence of cerebro-cerebellar circuits in ASD may be related with a cerebellar E/I imbalance.
American Journal of Physical Medicine & Rehabilitation
The aim of the study was to examine whether neural state of spared motor and premotor cortices ca... more The aim of the study was to examine whether neural state of spared motor and premotor cortices captured before a therapy predicts therapy-related motor gains in chronic subcortical stroke. Ten survivors, presenting chronic moderate upper limb impairment, underwent proton magnetic resonance spectroscopy, magnetic resonance imaging, clinical, and kinematics assessments before a 4-wk impairment-oriented training. Clinical/kinematics assessments were repeated after therapy, and motor gain was defined as positive values of clinical upper limb/elbow motion changes and negative values of trunk motion changes. Candidate predictors were N-acetylaspartate-neuronal marker, glutamate-glutamine-indicator of glutamatergic neurotransmission, and myo-inositol-glial marker, measured bilaterally within the upper limb territory in motor and premotor (premotor cortex, supplementary motor area) cortices. Traditional predictors (age, stroke length, pre-therapy upper limb clinical impairment, infarct volume) were also investigated. Poor motor gain was associated with lower glutamate-glutamine levels in ipsilesional primary motor cortex and premotor cortex (r = 0.77, P = 0.01 and r = 0.78, P = 0.008, respectively), lower N-acetylaspartate in ipsilesional premotor cortex (r = 0.69, P = 0.02), higher glutamate-glutamine in contralesional primary motor cortex (r = -0.68, P = 0.03), and lower glutamate-glutamine in contralesional supplementary motor area (r = 0.64, P = 0.04). These predictors outperformed myo-inositol metrics and traditional predictors (P ≈ 0.05-1.0). Glutamatergic state of bilateral motor and premotor cortices and neuronal state of ipsilesional premotor cortex may be important for predicting motor outcome in the context of a restorative therapy.
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Papers by Carmen Cirstea