Allan D. Wu

Non-invasive brain stimulation for Parkinson's disease: a systematic review and meta-analysis of the literature

A systematic review and meta-analysis were conducted to quantify the efficacy of transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) for the treatment of motor dysfunction in patients with Parkinson’s disease (PD). Prospective studies which evaluated the effects of either TMS (12 studies) or ECT (five studies) on motor function in PD using the motor subscale of the Unified Parkinson’s Disease Rating Scale (UPDRS) for TMS studies and any continuous measures of motor function in PD for ECT studies were included. The pooled effect size (standardised mean difference between pre-treatment versus post-treatment means) from a random effects model was 0.62 (95% confidence interval: 0.38, 0.85) for TMS treatment and 1.68 (0.79, 2.56) for ECT treatment, and from a fixed effects model was 0.59 (0.39, 0.78) for TMS treatment and 1.55 (1.07, 2.03) for ECT treatment. TMS, across applied stimulation sites and parameters, can exert a significant, albeit modest, positive effect on the motor function of patients with PD. ECT also may exert a significant effect on motor function in PD patients.

Motor Cortex Activation During Treatment May Predict Therapeutic Gains in Paretic Hand Function After Stroke

Background and Purpose— Functional brain imaging after stroke offers insight into motor network adaptations. This exploratory study examined whether motor cortical activation captured during arm-focused therapy can predict paretic hand functional gains. Methods— Eight hemiparetic patients had serial functional MRI (fMRI) while performing a pinch task before, midway, and after 2 weeks of constraint-induced therapy. The Wolf Motor Function Test (WMFT) was performed before and after intervention. Results— There was a linear reduction in ipsilateral (contralesional) primary motor (M1) activation (voxel counts) across time. The midpoint M1 Laterality Index anticipated post-therapeutic change in time to perform the WMFT. The change in ipsilateral M1 voxel count (pre- to mid-) correlated with the change in mean WMFT time (pre- to post-). Conclusions— The relationship between brain activation during treatment and functional gains suggests a use for serial fMRI in predicting the success and optimal duration for a focused therapeutic intervention.

Testing objective measures of motor impairment in early Parkinson's disease: Feasibility study of an at-home testing device.

We tested the feasibility of a computer based at‐home testing device (AHTD) in early‐stage, unmedicated Parkinsons disease (PD) patients over 6 months. We measured compliance, technical reliability, and patient satisfaction to weekly assessments of tremor, small and large muscle bradykinesia, speech, reaction/movement times, and complex motor control. relative to the UPDRS motor score. The AHTD is a 6.5″ × 10″ computerized assessment battery. Data are stored on a USB memory stick and sent by internet to a central data repository as encrypted data packets. Although not designed or powered to measure change, the study collected data to observe patterns relative to UPDRS motor scores. Fifty‐two PD patients enrolled, and 50 completed the 6 month trial, 48 remaining without medication. Patients complied with 90.6% of weekly 30‐minute assessments, and 98.5% of data packets were successfully transmitted and decrypted. On a 100‐point scale, patient satisfaction with the program at study end was 87.2 (range: 80–100). UPDRS motor scores significantly worsened over 6 months, and trends for worsening over time occurred for alternating finger taps (P = 0.08), tremor (P = 0.06) and speech (P = 0.11). Change in tremor was a significant predictor of change in UPDRS (P = 0.047) and was detected in the first month of the study. This new computer‐based technology offers a feasible format for assessing PD‐related impairment from home. The high patient compliance and satisfaction suggest the feasibility of its incorporation into larger clinical trials, especially when travel is difficult and early changes or frequent data collection are considered important to document.

Noninvasive brain stimulation for Parkinson's disease and dystonia.

SummaryRepetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are promising noninvasive cortical stimulation methods for adjunctive treatment of movement disorders. They avoid surgical risks and provide theoretical advantages of specific neural circuit neuromodulation. Neuromodulatory effects depend on extrinsic stimulation factors (cortical target, frequency, intensity, duration, number of sessions), intrinsic patient factors (disease process, individual variability and symptoms, state of medication treatment), and outcome measures. Most studies to date have shown beneficial effects of rTMS or tDCS on clinical symptoms in Parkinson’s disease (PD) and support the notion of spatial specificity to the effects on motor and nonmotor symptoms. Stimulation parameters have varied widely, however, and some studies are poorly controlled. Studies of rTMS or tDCS in dystonia have provided abundant data on physiology, but few on clinical effects. Multiple mechanisms likely contribute to the clinical effects of rTMS and tDCS in movement disorders, including normalization of cortical excitability, rebalancing of distributed neural network activity, and induction of dopamine release. It remains unclear how to individually adjust rTMS or tDCS factors for the most beneficial effects on symptoms of PD or dystonia. Nonetheless, the noninvasive nature, minimal side effects, positive effects in preliminary clinical studies, and increasing evidence for rational mechanisms make rTMS and tDCS attractive for ongoing investigation.

Do You See What I Mean? Corticospinal Excitability During Observation of Culture-Specific Gestures

People all over the world use their hands to communicate expressively. Autonomous gestures, also known as emblems, are highly social in nature, and convey conventionalized meaning without accompanying speech. To study the neural bases of cross-cultural social communication, we used single pulse transcranial magnetic stimulation (TMS) to measure corticospinal excitability (CSE) during observation of culture-specific emblems. Foreign Nicaraguan and familiar American emblems as well as meaningless control gestures were performed by both a Euro-American and a Nicaraguan actor. Euro-American participants demonstrated higher CSE during observation of the American compared to the Nicaraguan actor. This motor resonance phenomenon may reflect ethnic and cultural ingroup familiarity effects. However, participants also demonstrated a nearly significant (p = 0.053) actor by emblem interaction whereby both Nicaraguan and American emblems performed by the American actor elicited similar CSE, whereas Nicaraguan emblems performed by the Nicaraguan actor yielded higher CSE than American emblems. The latter result cannot be interpreted simply as an effect of ethnic ingroup familiarity. Thus, a likely explanation of these findings is that motor resonance is modulated by interacting biological and cultural factors.

Correlation between motor and phosphene thresholds: A transcranial magnetic stimulation study

Transcranial magnetic stimulation (TMS) has become a common tool for the brain mapping of a wide variety of cognitive functions. Because TMS over cortical regions of interest other than motor cortex often does not produce easily observable effects, the ability to calibrate TMS intensity for stimulation over nonmotor regions can be problematic. Previous studies reported no correlation between motor thresholds (MT) over the motor cortex and phosphene thresholds (PT) over the visual cortex. However, different thresholding methods, lighting, and eye‐closure conditions were used to determine MT and PT. We investigated the correlation between resting MT (rMT), active MT (aMT), and PT in 27 dark‐adapted healthy volunteers. All thresholds were measured with eyes‐open in the dark and determined by gradually reducing stimulation intensity downward. All subjects had aMT and rMT; 21 subjects had measurable PT. rMT was 70.4% ± 9.8% (mean ± SD of maximum stimulator output); aMT was 61.1% ± 7.9%; PT was 82.2% ± 10.1%. A significant positive correlation was found between aMT and PT (r = 0.53; P = 0.014) with a trend toward correlation between rMT and PT (r = 0.43; P = 0.052). Our results suggest that sensitivity to TMS over visual and motor cortices may be correlated under similar thresholding procedures. They also provide a rationale for the use of easily obtained aMT to calibrate TMS intensities in brain mapping studies that employ TMS in cortical regions besides motor cortex. Hum Brain Mapp, 2008.

Effect of Task Practice Order on Motor Skill Learning in Adults With Parkinson Disease: A Pilot Study

Background and Purpose: Random practice of motor tasks has been shown to enhance motor learning. The purpose of this study was to investigate the effects of task practice order (random, blocked) on motor learning in adults with Parkinson disease (PD). Subjects: Twenty adults with mild PD and 20 age-matched adults (controls) participated in the study. Methods: Participants in both groups (PD and control) practiced 3 movement tasks with either a blocked or a random practice order. This 2 participant group × 2 practice order design resulted in 4 experimental groups. The Trail Making Test was administered to all participants to determine task-switching capability. Motor performance on the arm movement tasks was quantified on the basis of the root-mean-square error difference between the goal movement task and each participants response. Results: The task-switching capability of the control group was superior to that of the PD group. For acquisition, in general, participants in the control group performed with significantly less error than participants in the PD group. For retention, participants in the control group who practiced with a random order performed more accurately than participants in the control group who practiced with a blocked order. However, for the PD group, the findings were reversed; participants who practiced with a blocked order performed more accurately than participants who practiced with a random order. These findings resulted in a group × practice order interaction. Discussion and Conclusion: These pilot study data suggest that, contrary to the findings for age-matched control learners, for learners with mild PD, a blocked practice order may be better than a random practice order for motor learning.

Anodal tDCS to V1 blocks visual perceptual learning consolidation.

This study examined the effects of visual cortex transcranial direct current stimulation (tDCS) on visual processing and learning. Participants performed a contrast detection task on two consecutive days. Each session consisted of a baseline measurement followed by measurements made during active or sham stimulation. On the first day, one group received anodal stimulation to primary visual cortex (V1), while another received cathodal stimulation. Stimulation polarity was reversed for these groups on the second day. The third (control) group of subjects received sham stimulation on both days. No improvements or decrements in contrast sensitivity relative to the same-day baseline were observed during real tDCS, nor was any within-session learning trend observed. However, task performance improved significantly from Day 1 to Day 2 for the participants who received cathodal tDCS on Day 1 and for the sham group. No such improvement was found for the participants who received anodal stimulation on Day 1, indicating that anodal tDCS blocked overnight consolidation of visual learning, perhaps through engagement of inhibitory homeostatic plasticity mechanisms or alteration of the signal-to-noise ratio within stimulated cortex. These results show that applying tDCS to the visual cortex can modify consolidation of visual learning.

Fast estimation of transcranial magnetic stimulation motor threshold.

BACKGROUND In Transcranial Magnetic Stimulation (TMS), the Motor Threshold (MT) is the minimum intensity required to evoke a liminal response in the target muscle. Because the MT reflects cortical excitability, the TMS intensity needs to be adjusted according to the subjects MT at the beginning of every TMS session. OBJECTIVE Shorten the MT estimation process compared to existing methods without compromising accuracy. METHODS We propose a Bayesian adaptive method for MT determination that incorporates prior MT knowledge and uses a stopping criterion based on estimation of MT precision. We compared the number of TMS pulses required with this new method with existing MT determination methods. RESULTS The proposed method achieved the accuracy of existing methods with as few as seven TMS pulses on average when using a common prior and three TMS pulses on average when using subject-specific priors. CONCLUSIONS Our adaptive Bayesian method is effective in reducing the number of pulses to estimate the MT.

Asymmetric corticomotor excitability correlations in early Parkinson's disease

We studied corticomotor excitability (CE) between the more and less affected sides in early Parkinsons disease (PD) patients using transcranial magnetic stimulation (TMS). Sixteen‐PD patients within the first 3 years of diagnosis were studied with single‐pulse TMS over each motor cortex with intensities from 40% to 100% stimulator output. Active motor evoked potentials (MEP) and cortical silent period durations (CSP) were recorded, fitted with sigmoid curves, summarized as maximal MEP/CSP, maximal MEP/CSP slope, and intensity where MEP/CSP is half‐maximal (MEP/CSP‐Int50), and correlated with Unified Parkinsons Disease Rating Scale scores (UPDRS). On the more affected side, higher (worse) UPDRS scores were correlated with shorter maximal CSP (r = −0.51, P = 0.046). On the less affected side, higher UPDRS scores were correlated with higher MEP‐Int50 (r = 0.51, P = 0.043) and CSP‐Int50 (r = 0.54, P = 0.029). For the less affected side, altered CE, as indexed by higher MEP or CSP‐Int50 intensities, may contribute to early clinical symptoms. On the more affected side, increases in CE, indexed by shorter CSP, may account for a greater proportion of PD symptoms. These findings are consistent with an evolution of neurophysiologic correlates in early PD patients from a less to more symptomatic state.