Woo-Kyoung Yoo

Repetitive Transcranial Magnetic Stimulation–Induced Corticomotor Excitability and Associated Motor Skill Acquisition in Chronic Stroke

Background and Purpose— Although there is some early evidence showing the value of repetitive transcranial magnetic stimulation (rTMS) in stroke rehabilitation, the therapeutic effect of high-frequency rTMS, along with the physiology of rTMS-induced corticomotor excitability supporting motor learning in stroke, has not been established. This study investigated high-frequency rTMS-induced cortical excitability and the associated motor skill acquisition in chronic stroke patients. Methods— Fifteen patients with chronic hemiparetic stroke (13 men; mean age 53.5 years) practiced a complex, sequential finger motor task using their paretic fingers either after 10 Hz or sham rTMS over the contralateral primary motor cortex (M1). Both the changes in the behavior and corticomotor excitability before and after the intervention were examined by measuring the movement accuracy, the movement time, and the motor-evoked potential (MEP) amplitude. A separate repeated-measures ANOVA and correlation statistics were used to determine the main and interaction effects as well as relationship between the changes in the behavioral and corticomotor excitability. Results— High-frequency rTMS resulted in a significantly larger increase in the MEP amplitude than the sham rTMS (P<0.01), and the plastic change was positively associated with an enhanced motor performance accuracy (P<0.05). Conclusions— High-frequency rTMS of the affected motor cortex can facilitate practice-dependent plasticity and improve the motor learning performance in chronic stroke victims.

Time-dependent effect of transcranial direct current stimulation on the enhancement of working memory.

The time-dependent effect of transcranial direct current stimulation (tDCS) on working memory was investigated by applying anodal stimulation over the left prefrontal cortex. This single-blind, sham-controlled crossover study recruited 15 healthy participants. A three-back verbal working-memory task was performed before, during, and 30 min after 1 mA anodal or sham tDCS. Anodal tDCS, compared with sham stimulation, significantly improved working-memory performance. Accuracy of response was significantly increased after 20 min of tDCS application, and was further enhanced after 30 min of stimulation. This effect was maintained for 30 min after the completion of stimulation. These results suggest that tDCS at 1 mA enhances working memory in a time-dependent manner for at least 30 min in healthy participants.

Plasticity of the Attentional Network After Brain Injury and Cognitive Rehabilitation

Background. This study aimed to delineate the cerebral attentional network in patients with traumatic brain injury (TBI) and assess for adaptations in this network in response to a rehabilitation intervention. Methods. Seventeen patients with TBI and 15 healthy subjects underwent functional magnetic resonance imaging (fMRI) using a visuospatial attention task. Ten TBI patients who successfully completed attentional training had a follow-up fMRI. Results. In the TBI patients, fMRI analysis showed more activation in the frontal and temporoparietal lobes, as well as less activation in the anterior cingulated gyrus, SMA, and temporooccipital regions compared to the healthy subjects. Following cognitive training, the TBI patients improved performance of attention tasks accompanied by changes in attentional network activation; the activity of the frontal lobe decreased, whereas activation of the anterior cingulate cortices and precuneus increased. Conclusions. These findings demonstrate the plasticity and training induced redistribution of the visuospatial attentional network in TBI patients.

High frequency rTMS modulation of the sensorimotor networks: Behavioral changes and fMRI correlates

Repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex (M1) may induce functional modulation of motor performance and sensory perception. To address the underlying neurophysiological modulation following 10 Hz rTMS applied over M1, we examined cortical activation using 3T functional magnetic resonance imaging (fMRI), as well as the associated motor and sensory behavioral changes. The motor performance measure involved a sequential finger motor task that was also used as an activation task during fMRI. For sensory assessment, current perception threshold was measured before and after rTMS outside the MR scanner, and noxious mechanical stimulation was used as an activation task during fMRI. We found that significant activation in the bilateral basal ganglia, left superior frontal gyrus, bilateral pre-SMA, right medial temporal lobe, right inferior parietal lobe, and right cerebellar hemisphere correlated with enhanced motor performance in subjects that received real rTMS compared with sham-stimulated controls. Conversely, significant deactivation in the right superior and middle frontal gyri, bilateral postcentral and bilateral cingulate gyri, left SMA, right insula, right basal ganglia, and right cerebellar hemisphere were associated with an increase in the sensory threshold. Our findings reveal that rTMS induced rapid changes in the sensorimotor networks associated with sensory perception and motor performance and demonstrate the complexity of such intervention.

Reproducibility of the effects of theta burst stimulation on motor cortical plasticity in healthy participants

OBJECTIVE Theta-burst stimulation (TBS) is a repetitive transcranial magnetic stimulation (TMS) protocol, capable of enhancing or suppressing the amplitude of contralateral motor-evoked potentials (MEP) for several minutes after stimulation over the primary motor cortex. Continuous TBS (cTBS) produces a long-term depression (LTD)-like reduction of cortical excitability. The purpose of this study was to assess the test-retest reproducibility of the effects of cTBS and to investigate which neurophysiologic markers of cTBS-induced plasticity are most reproducible. METHODS In ten healthy participants we evaluated in two different sessions the effects of cTBS (using AP-PA current direction, opposite to most commercial rTMS stimulators) on MEPs induced by single-pulse suprathreshold TMS (using AP-PA or PA current direction) over left motor cortex in the first dorsal interosseus (FDI) muscle. RESULTS Results demonstrate that the marker of cTBS induced-plasticity with highest within-subject reproducibility is the modulation of corticospinal excitability measured 5min after cTBS. CONCLUSION Overall the effects of cTBS modulation show limited test-retest reproducibility and some measures of the cTBS effects are more reproducible than others. SIGNIFICANCE Studies comparing cTBS effects in healthy subjects and patients need to proceed with care. Further characterization of the effects of TBS and identification of the best metrics warrant future studies.

Insights on the neural basis of motor plasticity induced by theta burst stimulation from TMS-EEG

Transcranial magnetic stimulation (TMS) is a useful tool to induce and measure plasticity in the human brain. However, the cortical effects are generally indirectly evaluated with motor‐evoked potentials (MEPs) reflective of modulation of cortico‐spinal excitability. In this study, we aim to provide direct measures of cortical plasticity by combining TMS with electroencephalography (EEG). Continuous theta‐burst stimulation (cTBS) was applied over the primary motor cortex (M1) of young healthy adults, and we measured modulation of (i) MEPs, (ii) TMS‐induced EEG evoked potentials (TEPs), (iii) TMS‐induced EEG synchronization and (iv) eyes‐closed resting EEG. Our results show the expected cTBS‐induced decrease in MEP size, which we found to be paralleled by a modulation of a combination of TEPs. Furthermore, we found that cTBS increased the power in the theta band of eyes‐closed resting EEG, whereas it decreased single‐pulse TMS‐induced power in the theta and alpha bands. In addition, cTBS decreased the power in the beta band of eyes‐closed resting EEG, whereas it increased single‐pulse TMS‐induced power in the beta band. We suggest that cTBS acts by modulating the phase alignment between already active oscillators; it synchronizes low‐frequency (theta and/or alpha) oscillators and desynchronizes high‐frequency (beta) oscillators. These results provide novel insight into the cortical effects of cTBS and could be useful for exploring cTBS‐induced plasticity outside of the motor cortex.

rTMS with motor training modulates cortico-basal ganglia-thalamocortical circuits in stroke patients.

BACKGROUND AND PURPOSE Repetitive transcranial magnetic stimulation (rTMS) may enhance plastic changes in the human cortex and modulation of behavior. However, the underlying neural mechanisms have not been sufficiently investigated. We examined the clinical effects and neural correlates of high-frequency rTMS coupled with motor training in patients with hemiparesis after stroke. METHODS Twenty-one patients were randomly divided into two groups, and received either real or sham rTMS. Ten daily sessions of 1,000 pulses of real or sham rTMS were applied at 10 Hz over the primary motor cortex of the affected hemisphere, coupled with sequential finger motor training of the paretic hand. Functional MRIs were obtained before and after training using sequential finger motor tasks, and performances were assessed. RESULTS Following rTMS intervention, movement accuracy of sequential finger motor tasks showed significantly greater improvement in the real group than in the sham group (p < 0.05). Real rTMS modulated areas of brain activation during performance of motor tasks with a significant interaction effect in the sensorimotor cortex, thalamus, and caudate nucleus. Patients in the real rTMS group also showed significantly enhanced activation in the affected hemisphere compared to the sham rTMS group. CONCLUSION According to these results, a 10 day course of high-frequency rTMS coupled with motor training improved motor performance through modulation of activities in the cortico-basal ganglia-thalamocortical circuits.

Tendinous insertion of semimembranosus muscle into the lateral meniscus

Forty-two cadaver knees were used for morphologic and MRI observations of the tendinous distal expansions of the semimembranosus m. and the posterior capsular structures of the knee. A tendinous branch of the semimembranosus m. inserting into the posterior horn of the lateral meniscus was found in 43.2% of the knees dissected, besides five already known insertional branches; capsular, direct, anterior and inferior, as well as the oblique popliteal ligament. The tendon had three morphologic types; thin, broad and round. All three types moved the lateral meniscus posteriorly when pulled on. Thus, the semimembranosus m. may also have a protective function for the lateral meniscus as well as the already well established function of protecting the medial meniscus in knee flexion. When a semimembranosus tendon attachment to the posterior horn of the lateral meniscus is present, its normal insertion is difficult to differentiate from a lateral meniscus tear in MRI and this may cause misdiagnosis.

Correlation of magnetic resonance diffusion tensor imaging and clinical findings of cervical myelopathy

BACKGROUND CONTEXT Despite significant advances in the development of diagnostic technology, the diagnosis of cervical myelopathy (CM) still remains based on the clinical findings, which do not provide the means for a sufficiently accurate diagnosis. Furthermore, conventional magnetic resonance imaging (MRI) using T1- and T2-weighted sequences lacks sensitivity to detect and characterize spinal cord lesions. Considering these uncertainties, several investigators have assessed the diagnostic value of diffusion tensor imaging (DTI), an advanced MRI technique that measures the diffusion of water molecules. PURPOSE To determine the diagnostic value of DTI in CM in reliably characterizing spinal lesions and in associating them with the clinical findings. STUDY DESIGN/SETTING Prospective cohort study. PATIENT SAMPLE Fifteen CM patients and five healthy volunteers without a history of neurological disorders or of symptoms as controls. OUTCOME MEASURES Symptoms and signs of CM were evaluated by the use of a modified Japanese Orthopedic Score and the other clinical findings. T2-weighed MRI was used to note the number of compressed levels. Diffusion tensor imaging results were measured according to two parameters, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), at anterior, lateral, and posterior regions of interest (ROIs) in each of five cervical vertebrae, C3-C7. METHODS On diagnosis of CM by clinical evaluation and findings from T2-weighted MRI, the 15 subjects were assigned to two subgroups based on complaints, symptoms, and signs. The nine subjects who had typical CM symptoms such as motor weakness, gait disturbance, clumsiness of the hands, and unilateral hypesthesia were assigned to the paralysis subgroup. The other six subjects, whose main symptom was pain and who had vague signs of upper motor neuron injury despite a definitive finding of CM by T2-weighted MRI, were assigned to the pain subgroup. Once assignments had been made, subjects underwent DTI done by the use of the same scanner as for T2-weighted MRI. Results of DTI for each subgroup and controls were averaged, and the mean was used for comparisons. Diffusion tensor imaging results from the paralysis subgroup were sorted into affected and unaffected sides according to the presence or the absence of symptoms. RESULTS The paralysis subgroup and the pain subgroup had similar findings from T2-weighted MRI on presentation. The paralysis subgroup had statistically significantly decreased FA values in the anterior and lateral ROIs on the affected side and in the anterior ROIs on the unaffected side, compared with controls. The paralysis subgroup also had statistically significantly increased ADC values in the anterior ROIs of the affected side, compared with controls. The pain subgroup showed significantly increased ADC values in anterior, lateral, and posterior ROIs. CONCLUSIONS Use of DTI to quantitatively compare compression in the cervical spinal cords of CM subjects and healthy controls explained individual differences in the clinical findings in the subjects. These findings even applied to CM subjects whose compressed spinal cords looked similar on conventional T2-weighted MRI. Therefore, DTI provided more accurate and reliable information than did conventional T2-weighted MRI about the relationship between spinal cord structure and clinical presentation of CM. Based on our DTI findings, we hypothesized that different clinical findings in CM are attributable to the stage of progression and the severity of pathologic change at presentation. We anticipate that the use of DTI to quantify the extent of myelopathological changes in CM could be more reliable than any other existing diagnostic tools and might provide invaluable information about selecting the optimal treatment for CM and predicting surgical outcomes and prognosis.

Changes in cortical plasticity after mild traumatic brain injury

PURPOSE Even after a mild traumatic brain injury (TBI) symptoms may be long lasting and never resolve completely. The neurophysiologic substrate for such lasting deficits remains unclear. There is a lack of objective measures of early brain abnormalities following mild TBI, which could shed light on the genesis of these lasting impairments. METHODS Here we report findings in a previously healthy man tested 2 and 6 weeks after a well-documented concussion. Findings were compared with 12 control subjects. All subjects underwent brain magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI). Testing included neuropsychological evaluation and physiological assessment with TMS and EEG, excitatory/inhibitory balance and brain plasticity. RESULTS While the MRI, DTI and neuropsychological evaluations showed no abnormalities, neurophysiologic tests revealed subclinical abnormalities in our patient: (1) Significantly higher intracortical facilitation than the control group at both time points; (2) Intracortical inhibition presumably mediated by GABAB receptors was absent at week 2, but returned to normal value at week 6; (3) Abnormal mechanisms of plasticity at week 2, that normalize at week 6. CONCLUSIONS These findings demonstrate a transient alteration of brain cortical physiology following concussion independent of anatomical findings and neuropsychological function. This case study suggests that TMS measures may serve as sensitive biomarkers of physiologic brain abnormalities after concussion.