Elise Houdayer

Prediction of human voluntary movement before it occurs.

OBJECTIVE Human voluntary movement is associated with two changes in electroencephalography (EEG) that can be observed as early as 1.5 s prior to movement: slow DC potentials and frequency power shifts in the alpha and beta bands. Our goal was to determine whether and when we can reliably predict human natural movement BEFORE it occurs from EEG signals ONLINE IN REAL-TIME. METHODS We developed a computational algorithm to support online prediction. Seven healthy volunteers participated in this study and performed wrist extensions at their own pace. RESULTS The average online prediction time was 0.62±0.25 s before actual movement monitored by EMG signals. There were also predictions that occurred without subsequent actual movements, where subjects often reported that they were thinking about making a movement. CONCLUSION Human voluntary movement can be predicted before movement occurs. SIGNIFICANCE The successful prediction of human movement intention will provide further insight into how the brain prepares for movement, as well as the potential for direct cortical control of a device which may be faster than normal physical control.

Intermittent theta-burst transcranial magnetic stimulation for treatment of Parkinson disease

Objective: To investigate the safety and efficacy of intermittent theta-burst stimulation (iTBS) in the treatment of motor symptoms in Parkinson disease (PD). Background: Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS. Methods: In this randomized, double-blind, sham-controlled study, we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks (evidence Class I). Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinsons Disease Rating Scale (UPDRS), and additional clinical, neuropsychological, and neurophysiologic measures. Results: We investigated 26 patients with mild to moderate PD: 13 received iTBS and 13 sham stimulation. We found beneficial effects of iTBS on mood, but no improvement of gait, bradykinesia, UPDRS, and other measures. EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity. Few reported discomfort or pain and one experienced tinnitus during real stimulation. Conclusion: iTBS of the motor and prefrontal cortices appears safe and improves mood, but failed to improve motor performance and functional status in PD. Classification of evidence: This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD.

Afferent‐induced facilitation of primary motor cortex excitability in the region controlling hand muscles in humans

Sensory inputs from cutaneous and limb receptors are known to influence motor cortex network excitability. Although most recent studies have focused on the inhibitory influences of afferent inputs on arm motor responses evoked by transcranial magnetic stimulation (TMS), facilitatory effects are rarely considered. In the present work, we sought to establish how proprioceptive sensory inputs modulate the excitability of the primary motor cortex region controlling certain hand and wrist muscles. Suprathreshold TMS pulses were preceded either by median nerve stimulation (MNS) or index finger stimulation with interstimulus intervals (ISIs) ranging from 20 to 200 ms (with particular focus on 40–80 ms). Motor‐evoked potentials recorded in the abductor pollicis brevis (APB), first dorsalis interosseus and extensor carpi radialis muscles were strongly facilitated (by up to 150%) by MNS with ISIs of around 60 ms, whereas digit stimulation had only a weak effect. When MNS was delivered at the interval that evoked the optimal facilitatory effect, the H‐reflex amplitude remained unchanged and APB motor responses evoked with transcranial electric stimulation were not increased as compared with TMS. Afferent‐induced facilitation and short‐latency intracortical inhibition (SICI) and intracortical facilitation (ICF) mechanisms are likely to interact in cortical circuits, as suggested by the strong facilitation observed when MNS was delivered concurrently with ICF and the reduction of SICI following MNS. We conclude that afferent‐induced facilitation is a mechanism which probably involves muscle spindle afferents and should be considered when studying sensorimotor integration mechanisms in healthy and disease situations.

Controlled Study of 50-Hz Repetitive Transcranial Magnetic Stimulation for the Treatment of Parkinson Disease

Objective. To investigate the safety and efficacy of 50-Hz repetitive transcranial magnetic stimulation (rTMS) in the treatment of motor symptoms in Parkinson disease (PD). Background. Progression of PD is characterized by the emergence of motor deficits that gradually respond less to dopaminergic therapy. rTMS has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. Prior controlled studies suggest that an increase in stimulation frequency might enhance therapeutic efficacy. Methods. In this randomized, double blind, sham-controlled study, the authors investigated the safety and efficacy of 50-Hz rTMS of the motor cortices in 8 sessions over 2 weeks. Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson’s Disease Rating Scale (UPDRS), and additional clinical, neurophysiological, and neuropsychological parameters. In addition, the safety of 50-Hz rTMS was tested with electromyography-electroencephalogram (EMG-EEG) monitoring during and after stimulation. Results. The authors investigated 26 patients with mild to moderate PD: 13 received 50-Hz rTMS and 13 sham stimulation. The 50-Hz rTMS did not improve gait, bradykinesia, and global and motor UPDRS, but there appeared a short-lived “on”-state improvement in activities of daily living (UPDRS II). The 50-Hz rTMS lengthened the cortical silent period, but other neurophysiological and neuropsychological measures remained unchanged. EMG/EEG recorded no pathological increase of cortical excitability or epileptic activity. There were no adverse effects. Conclusion. It appears that 50-Hz rTMS of the motor cortices is safe, but it fails to improve motor performance and functional status in PD. Prolonged stimulation or other techniques with rTMS might be more efficacious but need to be established in future research.

The role of inhibition from the left dorsal premotor cortex in right-sided focal hand dystonia.

BACKGROUND The left dorsal premotor cortex (PMd) plays an important role in movement selection and is abnormally activated in imaging studies in patients with right-sided focal hand dystonia (FHD). OBJECTIVE The aims of this study were to assess the role of left PMd in patients with FHD and in the genesis of surround inhibition, which is deficient in FHD. METHODS Single- and paired-pulse transcranial magnetic stimulation (TMS) was applied during different phases of an index finger movement using the abductor pollicis brevis muscle (APB), a surrounding, nonsynergistic muscle, as target muscle. To look at the effect of PMd on the primary motor cortex (M1), a subthreshold conditioning pulse was applied to PMd 6 milliseconds before stimulation over M1. RESULTS There was surround inhibition during movement initiation in controls, but not in FHD patients. In contrast, FHD patients, but not controls, showed premotor-motor inhibition (PMI) at rest. During movement, PMI was absent in both groups. CONCLUSIONS We conclude that PMI does not appear to play a key role in the formation of surround inhibition in normal subjects, because it was not enhanced during movement initiation. However, in FHD, inhibition from PMd on M1 was abnormally increased at rest and declined during movement initiation. The behavior of PMd can therefore partly explain the loss of surround inhibition in the FHD patients. The functional significance of increased PMI at rest is not clear, but might be an attempt of compensation for losses of inhibition from other brain areas.

Safety study of 50 Hz repetitive transcranial magnetic stimulation in patients with Parkinson's disease.

OBJECTIVE Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in treating Parkinsons disease (PD), but the best values for rTMS parameters are not established. Fifty Hertz rTMS may be superior to 25 Hz rTMS investigated so far. The objective of this study was to determine if 50 Hz rTMS could be delivered safely in PD patients since current safety limits are exceeded. METHODS Fifty Hertz rTMS was applied with a circular coil on the primary motor cortex (M1). Stimulation intensity was first tested at 60% rest motor threshold [RMT] and 0.5 s train duration and then increased in 0.5 s steps to 2 s, and by 10% steps to 90% RMT. Multi-channel electromyography (EMG) was recorded to control for signs of increasing time-locked EMG activity including correlates of the spread of excitation and after-discharges, or an increase of M1 excitability. Pre- and post-50 Hz rTMS assessments included EEG, Unified Parkinson Disease Rating Scale (UPDRS), Grooved Pegboard Test, Serial Reaction Time Task (SRTT), Folstein Mini-Mental Status Examination (MMSE) and Verbal Fluency to control for motor and cognitive side effects. RESULTS Ten PD patients were investigated. Multi-channel EMG showed no signs of increased time-locked EMG activity including correlates of the spread of excitation and after-discharges, or increased M1 excitability in 9 patients. A PD patient with bi-temporal spikes in the pre-testing EEG had clinical and EMG correlates of spread of excitation at 90% RMT, but no seizure activity. Pre- and post-50 Hz assessment showed no changes. No adverse events were observed. Fifty Hertz rTMS was well tolerated except by 1 patient who wished to terminate the study due to facial muscle stimulation. CONCLUSION Fifty Hertz rTMS at an intensity of 90% RMT for 2 s appears safe in patients with PD, but caution should be taken for patients with paroxysmal EEG activity. For this reason, comprehensive screening should include EEG before higher-frequency rTMS is applied. SIGNIFICANCE This is the first study to investigate safety of 50 Hz rTMS in humans.

Excitatory deep repetitive transcranial magnetic stimulation with H-coil as add-on treatment of motor symptoms in Parkinson's disease: an open label, pilot study.

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a potential treatment for Parkinsons disease (PD). H-coils, inducing deeper and wider magnetic fields compared to traditional coils, may be potentially useful in PD, characterized by widespread, bilateral involvement of cortico-subcortical circuits. OBJECTIVE To evaluate the safety of repetitive deep TMS (rDTMS) with H-coil as add-on treatment of motor symptoms in PD. METHODS Twenty-seven PD patients (aged 60.1 ± 6.8 y; PD-duration: 6.3 ± 2.8 y; motor-UPDRS: 39.6 ± 10.1) underwent 12 rDTMS sessions over 4 weeks at excitatory (10 Hz) frequency over primary motor (M1) and bilateral prefrontal (PF) regions. Motor UPDRS off therapy was assessed before and after the last rDTMS session, together with safety records at each treatment session. RESULTS No drop-outs or adverse events were recorded. Motor UPDRS significantly improved after rDTMS (10.8 points average reduction; P < 0.0001). CONCLUSIONS High-frequency rDTMS might be a safe treatment for PD motor symptoms. Further placebo-controlled, randomized studies are warranted.

Use of swLORETA to localize the cortical sources of target- and distracter-elicited P300 components

OBJECTIVE Cognitive event-related potentials (especially P300) have long been used to explore attentional processes. The aim of this study was to identify the cortical areas involved in P300 generation during a selective attention task. METHODS 128 channel electroencephalograms were recorded in 15 healthy controls performing a three-stimulus visual oddball paradigm, in order to identify distracter- and target-elicited P300 components. For each subject, the P300 sources were localized using standardized weighted low-resolution electromagnetic tomography (swLORETA). One sample and paired T-tests were performed using SPM5®. RESULTS Common sources for both P300 components were observed within a large frontoparietal network, including the frontal eye field and dorsal parietal cortex (i.e. the attentional dorsal frontoparietal network). More inferior parietal areas, prefrontal and cingulate cortices (i.e. the attentional ventral frontoparietal network) were also involved in the generation of target-elicited P300. CONCLUSIONS These results suggest that distracter- and target-elicited P300 are both generated by the dorsal frontoparietal network. Moreover, target processing recruits a specific ventral network. SIGNIFICANCE Our data agree with the literature reports using other methods and should help to improve our knowledge of the cerebral networks underlying attentional processes.

Effect of dopaminergic substances on sleep/wakefulness in saline- and MPTP-treated mice.

Sleep/wakefulness (S/W) disorders are frequent in Parkinson’s disease (PD). The underlying causes have yet to be elucidated but dopaminergic neurodegenerative lesions seem to contribute to appearance of the disorders and anti‐Parkinsonian medication is known to accentuate S/W problems. Hence, we reasoned that studying the acute effect of dopaminergic compounds on S/W in an animal model of PD might improve our knowledge of S/W regulation in the context of partial dopaminergic depletion. To this end, we tested the effect of levodopa (l‐dopa), pergolide (a mixed D2/D1 agonist) and lisuride (a D2 agonist) on S/W recordings in MPTP‐treated mice, in comparison with controls. Our results showed that dopaminergic compounds modify S/W amounts in both control and MPTP mice. Wakefulness amounts are greater in MPTP mice after l‐dopa (50 mg kg−1) and lisuride (1 mg kg−1) injections compared with control mice. Moreover, the paradoxical sleep latency was significantly longer in MPTP mice after high‐dose l‐dopa administration. Our observations suggest that the actions of both l‐dopa and lisuride on S/W differ slightly in MPTP mice relative to controls. Hence, MPTP‐induced partial DA depletion may modulate the effect of dopaminergic compounds on S/W regulation.

The differential modulation of the ventral premotor-motor interaction during movement initiation is deficient in patients with focal hand dystonia.

A major feature of focal hand dystonia (FHD) pathophysiology is the loss of inhibition. One inhibitory process, surround inhibition, for which the cortical mechanisms are still unknown, is abnormal in FHD. As the ventral premotor cortex (PMv) plays a key role in the sensorimotor processing involved in shaping finger movements and has many projections onto the primary motor cortex (M1), we hypothesized that the PMv–M1 connections might play a role in surround inhibition. A paired‐pulse transcranial magnetic stimulation paradigm was used in order to evaluate and compare the PMv–M1 interactions during different phases (rest, preparation and execution) of an index finger movement in patients with FHD and controls. A sub‐threshold conditioning pulse (80% resting motor threshold) was applied to the PMv at 6 ms before M1 stimulation. The right abductor pollicis brevis, a surround muscle, was the target muscle. In healthy controls, the results showed that PMv stimulation induced an ipsilateral ventral premotor–motor inhibition at rest. This cortico‐cortical interaction changed into an early facilitation (100 ms before movement onset) and turned back to inhibition 50 ms later. In patients with FHD, this PMv–M1 interaction and its modulation were absent. Our results show that, although the ipsilateral ventral premotor–motor inhibition does not play a key role in the genesis of surround inhibition, PMv has a dynamic influence on M1 excitability during the early steps of motor execution. The impaired cortico‐cortical interactions observed in patients with FHD might contribute, at least in part, to the abnormal motor command.