Background. Abnormal brain excitability influences recovery after stroke at which time a prolonged transcranial magnetic stimulation (TMS)-induced electromyographic silent period is thought to reflect abnormal inhibitory interneuron excitability. Cortical excitability can be probed directly during the silent period using concurrent electroencephalography (EEG) of TMS-evoked responses. Objective. The primary study objectives were to characterize TMS-evoked cortical potentials (TEPs) using EEG and to investigate associations with persistent hand and arm motor dysfunction in individuals with chronic stroke. Methods. Thirteen participants with chronic stroke-related mild-moderate arm motor impairment and 12 matched controls completed a single TMS-EEG cortical excitability assessment. TEPs recorded from the vertex during cortical silent period (CSP) assessment and while at rest were used to evaluate differences in cortical excitability between stroke and control participants. Associations between TEPs and CSP duration with measures of upper extremity motor behavior were investigated. Results. Significantly increased TEP component peak amplitudes and delayed latencies were observed for stroke participants compared with controls during CSP assessment and while at rest. Delayed early TEP component (P30) peak latencies during CSP assessment were associated with less manual dexterity. CSP duration was prolonged in stroke participants, and correlated with P30 peak latency and paretic arm dysfunction. Conclusions. Abnormal cortical excitability directly measured by early TMS-evoked EEG responses during CSP assessment suggests abnormal cortical inhibition is associated with hand dysfunction in chronic stroke. Further investigation of abnormal cortical inhibition in specific brain networks is necessary to characterize the salient neurophysiologic mechanisms contributing to persistent motor dysfunction after stroke.
by
Bimal Lakhani;
Michael Borich;
Jacob N. Jackson;
Katie P. Wadden;
Sue Peters;
Anica Villamayor;
Alex L. MacKay;
Irene M. Vavasour;
Alexander Rauscher;
Lara A. Boyd
Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI), the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent change. In the current study, seventeen healthy young adults completed ten sessions of visuomotor skill training (10,000 total movements) using the right arm. Multicomponent relaxation imaging was performed before and after training. Significant increases in myelin water fraction, a quantitative measure of myelin, were observed in task dependent brain regions (left intraparietal sulcus [IPS] and left parieto-occipital sulcus). In addition, the rate of motor skill acquisition and overall change in myelin water fraction in the left IPS were negatively related, suggesting that a slower rate of learning resulted in greater neuroplastic change. This study provides the first evidence for experience-dependent changes in myelin that are associated with changes in skilled movements in healthy young adults.
Primary motor cortex (M1) plasticity is involved in motor learning and stroke motor recovery, and enhanced by increasing monoaminergic transmission. Age impacts these processes but there is a paucity of systematic studies on the effects of monoaminergic drugs in older adults. Here, in ten older adults (age 61 + 4 years, 4 males), we determine the effects of a single oral dose of carbidopa/levodopa (DOPA), D-amphetamine (AMPH), methylphenidate (MEPH) and placebo (PLAC) on M1 excitability and motor training-induced M1 plasticity. M1 plasticity is defined as training related long lasting changes in M1 excitability and kinematics of the trained movement. At peak plasma level of the drugs, subjects trained wrist extension movements for 30 min. Outcome measures were motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation at increasing intensity (stimulus response curve, SRC) and peak acceleration of the trained wrist extension movements. Measures were obtained before and after completion of training. The curve parameters plateau (MEPmax), inflection point, and slope were extracted from SRC. At baseline drugs had a differential effect on curve parameters, while kinematics remained unchanged. Training alone (PLAC) increased MEPmax but did not improve kinematics. Drugs affected training-related changes of the curve parameters differently, but did not enhance them or kinematics when compared to PLAC. The results demonstrate that in the older adults, MEPH, DOPA, or AMPH have differential effects on baseline M1 excitability and training-related M1 plasticity but fail to enhance them above the naïve level.
Neuroplasticity is a fundamental yet relatively unexplored process that can impact rehabilitation of lower extremity (LE) movements. Transcranial magnetic stimulation (TMS) has gained widespread application as a non-invasive brain stimulation technique for evaluating neuroplasticity of the corticospinal pathway. However, a majority of TMS studies have been performed on hand muscles, with a paucity of TMS investigations focused on LE muscles. This perspective review paper proposes that there are unique methodological challenges associated with using TMS to evaluate corticospinal excitability of lower limb muscles. The challenges include: (1) the deeper location of the LE motor homunculus; (2) difficulty with targeting individual LE muscles during TMS; and (3) differences in corticospinal circuity controlling upper and lower limb muscles. We encourage future investigations that modify traditional methodological approaches to help address these challenges. Systematic TMS investigations are needed to determine the extent of overlap in corticomotor maps for different LE muscles. A simple, yet informative methodological solution involves simultaneous recordings from multiple LE muscles, which will provide the added benefit of observing how other relevant muscles co-vary in their responses during targeted TMS assessment directed toward a specific muscle. Furthermore, conventionally used TMS methods (e.g., determination of hot spot location and motor threshold) may need to be modified for TMS studies involving LE muscles. Additional investigations are necessary to determine the influence of testing posture as well as activation state of adjacent and distant LE muscles on TMS-elicited responses. An understanding of these challenges and solutions specific to LE TMS will improve the ability of neurorehabilitation clinicians to interpret TMS literature, and forge novel future directions for neuroscience research focused on elucidating neuroplasticity processes underlying locomotion and gait training.
Emerging evidence indicates impairments in somatosensory function may be a major contributor to motor dysfunction associated with neurologic injury or disorders. However, the neuroanatomical substrates underlying the connection between aberrant sensory input and ineffective motor output are still under investigation. The primary somatosensory cortex (S1) plays a critical role in processing afferent somatosensory input and contributes to the integration of sensory and motor signals necessary for skilled movement. Neuroimaging and neurostimulation approaches provide unique opportunities to non-invasively study S1 structure and function including connectivity with other cortical regions. These research techniques have begun to illuminate casual contributions of abnormal S1 activity and connectivity to motor dysfunction and poorer recovery of motor function in neurologic patient populations. This review synthesizes recent evidence illustrating the role of S1 in motor control, motor learning and functional recovery with an emphasis on how information from these investigations may be exploited to inform stroke rehabilitation to reduce motor dysfunction and improve therapeutic outcomes.
Introduction: Hemiparesis is one of the most prevalent chronic disabilities after stroke. Biochemical and structural magnetic resonance imaging approaches may be employed to study the neural substrates underpinning upper-extremity (UE) recovery after chronic stroke.
Objective: The purposes of this study were to 1) quantify anatomical and metabolic differences in the precentral gyrus, and 2) test the relationships between anatomical and metabolic differences, and hemiparetic arm function in individuals in the chronic stage of stroke recovery. Our hypotheses were: 1) the Stroke group would exhibit reduced precentral gyrus cortical thickness and lower concentrations of total N-acetylaspartate (tNAA) and glutamate+glutamine (Glx) in the ipsilesional motor cortex; and 2) that each of these measures would be associated with UE motor function after stroke.
Methods: Seventeen individuals with chronic (>6 months) subcortical ischemic stroke and eleven neurologically healthy controls were recruited. Single voxel proton magnetic resonance spectroscopy (H1MRS) was performed to measure metabolite concentrations of tNAA and Glx in the precentral gyrus in both ipsilesional and contralesional hemispheres. Surface-based cortical morphometry was used to quantify precentral gyral thickness. Upper-extremity motor function was assessed using the Wolf Motor Function Test (WMFT).
Results
Results demonstrated significantly lower ipsilesional tNAA and Glx concentrations and precentral gyrus thickness in the Stroke group. Ipsilesional tNAA and Glx concentration and precentral gyrus thickness was significantly lower in the ipsilesional hemisphere in the Stroke group. Parametric correlation analyses revealed a significant positive relationship between precentral gyrus thickness and tNAA concentration bilaterally. Multivariate regression analyses revealed that ipsilesional concentrations of tNAA and Glx predicted the largest amount of variance in WMFT scores. Cortical thickness measures alone did not predict a significant amount of variance in WMFT scores.
Conclusions: While stroke impairs both structure and biochemistry in the ipsilesional hemisphere our data suggest that tNAA has the strongest relationship with motor function.
Integration of sensory and motor information is one-step, among others, that underlies the successful production of goal-directed hand movements necessary for interacting with our environment. Disruption of sensorimotor integration is prevalent in many neurologic disorders, including stroke. In most stroke survivors, persistent paresis of the hand reduces function and overall quality of life. Current rehabilitative methods are based on neuroplastic principles to promote motor learning that focuses on regaining motor function lost due to paresis, but the sensory contributions to motor control and learning are often overlooked and currently understudied. There is a need to evaluate and understand the contribution of both sensory and motor function in the rehabilitation of skilled hand movements after stroke. Here, we will highlight the importance of integration of sensory and motor information to produce skilled hand movements in healthy individuals and individuals after stroke. We will then discuss how compromised sensorimotor integration influences relearning of skilled hand movements after stroke. Finally, we will propose an approach to target sensorimotor integration through manipulation of sensory input and motor output that may have therapeutic implications.
Summary: Background: Patients with Diabetes are at greater risk for ischemic stroke and usually suffer more severe ischemic brain damage than nondiabetic patients. However, the underlying mechanism of the exaggerated injury is not well defined. Aims: Macroautophagy (hereafter called autophagy in this report) plays a key role in cellular homeostasis and may contribute to cell death as well. Our aim was to determine whether autophagy was involved in the enhanced susceptibility of diabetic brain cells to ischemic injury and explore it as a possible target for the treatment of stroke in a diabetic condition. Results: A type II diabetic mouse model generated by combined administration of streptozotocin and nicotinamide showed enlarged infarct volume, increased cell death and excessive blood-brain barrier (BBB) disruption compared with nondiabetic stroke mice. After ischemic stroke, both diabetic and nondiabetic mice showed enhanced autophagosome formation and autophagic flux as demonstrated by increased expression of autophagy signals Beclin 1, microtubule-associated protein light-chain II (LC3-II), and decreased autophagy-specific substrate p62. The increased autophagic activity was significantly higher in diabetic stroke mice than that in nondiabetic stroke mice. The autophagy inhibitor 3-methyladenine (3-MA) attenuated the exaggerated brain injury and improved functional recovery. Conclusions: These data suggest that autophagy contributes to exacerbated brain injury in diabetic condition, and autophagy-mediated cell death may be a therapeutic target in diabetic stroke.
BACKGROUND: The use of transcranial magnetic stimulation (TMS) to evaluate corticomotor excitability of lower limb (LL) muscles can provide insights about neuroplasticity mechanisms underlying LL rehabilitation. However, to date, a majority of TMS studies have focused on upper limb muscles. Posture-related activation is an important under-investigated factor influencing corticomotor excitability of LL muscles. OBJECTIVE: The purpose of this study was to evaluate effects of posture and background activation on corticomotor excitability of ankle muscles. METHODS: Fourteen young neurologically-unimpaired participants (26.1±4.1 years) completed the study. TMS-evoked motor evoked potentials (MEPs) were recorded from the tibialis anterior (TA) and soleus during 4 conditions - standing, standing coactivation, sitting, and sitting coactivation. TA and soleus MEP amplitudes were compared during: (1) standing versus sitting;(2) standing coactivation (standing while activating both TA and soleus) versus sitting coactivation; and (3) standing coactivation versus standing. For each comparison, background EMG for TA and soleus were matched. Trial-to-trial coefficient of variation of MEP amplitude and coil-positioning errors were additional dependent variables. RESULTS: No differences were observed in TA or soleus MEP amplitudes during standing versus sitting. Compared to sitting coactivation, larger MEPs were observed during standing coactivation for soleus but not TA. Compared to standing, the standing coactivation task demonstrated larger MEPs and reduced trial-to-trial MEP variability. CONCLUSION: Our findings suggest that incorporation of measurements in standing in future TMS studies may provide novel insights into neural circuits controlling LL muscles. Standing and standing coactivation tasks may be beneficial for obtaining functionally-relevant neuroplasticity assessments of LL musculature.
OBJECTIVE: Constraint-induced movement therapy (CIMT) has been shown to improve upper extremity voluntary movement and change cortical movement representation after stroke. Direct comparison of the differential degree of cortical reorganization according to chronicity in stroke subjects receiving CIMT has not been performed and was the purpose of this study. We hypothesized that a higher degree of cortical reorganization would occur in the early (less than 9 months post-stroke) compared to the late group (more than 12 months post-stroke).
METHODS: 17 early and 9 late subjects were enrolled. Each subject was evaluated using transcranial magnetic stimulation (TMS) and the Wolf Motor Function Test (WMFT) and received CIMT for 2 weeks.
RESULTS: The early group showed greater improvement in WMFT compared with the late group. TMS motor maps showed persistent enlargement in both groups but the late group trended toward more enlargement. The map shifted posteriorly in the late stroke group. The main limitation was the small number of TMS measures that could be acquired due to high motor thresholds, particularly in the late group.
CONCLUSION: CIMT appears to lead to greater improvement in motor function in the early phase after stroke. Greater cortical reorganization in map size and position occurred in the late group in comparison.
SIGNIFICANCE: The contrast between larger functional gains in the early group vs larger map changes in the late group may indicate that mechanisms of recovery change over the several months following stroke or that map changes are a time-dependent epiphenomenon.