Background: the use of combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) for the functional evaluation of the cerebral cortex in health and disease is becoming increasingly common. However, there is still some ambiguity regarding the extent to which brain responses to auditory and somatosensory stimulation contribute to the TMS-evoked potential (TEP). Objective/Hypothesis: to measure separately the contribution of auditory and somatosensory stimulation caused by TMS, and to assess their contribution to the TEP waveform, when stimulating the motor cortex (M1). Methods: 19 healthy volunteers underwent 7 blocks of EEG recording. To assess the impact of auditory stimulation on the TEP waveform, we used a standard figure of eight coil, with or without masking with a continuous noise reproducing the specific time-varying frequencies of the TMS click, stimulating at 90% of resting motor threshold. To further characterise auditory responses due to the TMS click, we used either a standard or a sham figure of eight coil placed on a pasteboard cylinder that rested on the scalp, with or without masking. Lastly, we used electrical stimulation of the scalp to investigate the possible contribution of somatosensory activation. Results: auditory stimulation induced a known pattern of responses in electrodes located around the vertex, which could be suppressed by appropriate noise masking. Electrical stimulation of the scalp alone only induced similar, non-specific scalp responses in the in the central electrodes. TMS, coupled with appropriate masking of sensory input, resulted in specific, lateralized responses at the stimulation site, lasting around 300 ms. Conclusions: if careful control of confounding sources is applied, TMS over M1 can generate genuine, lateralized EEG activity. By contrast, sensory evoked responses, if present, are represented by nonspecific, late (100e200 ms) components, located at the vertex, possibly due to saliency of the stimuli. Notably, the latter can confound the TEP if masking procedures are not properly used.
The efficacy of standard rehabilitative therapy for improving upper limb functions after stroke is limited; thus, alternative strategies are needed. Vagus nerve stimulation (VNS) paired with rehabilitation is a promising approach, but the invasiveness of this technique limits its clinical application. Recently, a noninvasive method to stimulate vagus nerve has been developed. The aim of the present study was to explore whether noninvasive VNS combined with robotic rehabilitation can enhance upper limb functionality in chronic stroke. Safety and efficacy of this combination have been assessed within a proof-of-principle, double-blind, semirandomized, sham-controlled trial. Fourteen patients with either ischemic or haemorrhagic chronic stroke were randomized to robot-assisted therapy associated with real or sham VNS, delivered for 10 working days. Efficacy was evaluated by change in upper extremity Fugl–Meyer score. After intervention, there were no adverse events and Fugl–Meyer scores were significantly better in the real group compared to the sham group. Our pilot study confirms that VNS is feasible in stroke patients and can produce a slight clinical improvement in association to robotic rehabilitation. Compared to traditional stimulation, noninvasive VNS seems to be safer and more tolerable. Further studies are needed to confirm the efficacy of this innovative approach.
The aim of this review is to summarize that most relevant technologies used to evaluate gait features and the associated algorithms that have shown promise to aid diagnosis and symptom monitoring in Parkinson’s disease (PD) patients. We searched PubMed for studies published between 1 January 2005, and 30 August 2019 on gait analysis in PD. We selected studies that have either used technologies to distinguish PD patients from healthy subjects or stratified PD patients according to motor status or disease stages. Only those studies that reported at least 80% sensitivity and specificity were included. Gait analysis algorithms used for diagnosis showed a balanced accuracy range of 83.5–100%, sensitivity of 83.3–100% and specificity of 82–100%. For motor status discrimination the gait analysis algorithms showed a balanced accuracy range of 90.8–100%, sensitivity of 92.5–100% and specificity of 88–100%. Despite a large number of studies on the topic of objective gait analysis in PD, only a limited number of studies reported algorithms that were accurate enough deemed to be useful for diagnosis and symptoms monitoring. In addition, none of the reported algorithms and technologies has been validated in large scale, independent studies.
Background: Pulses of transcranial magnetic stimulation (TMS) with a predominantly anterior-posterior (AP) or posterior-anterior (PA) current direction over the primary motor cortex appear to activate distinct excitatory inputs to corticospinal neurons. In contrast, very few reports have examined whether the inhibitory neurons responsible for short-interval intracortical inhibition (SICI) are sensitive to TMS current direction. Objectives: To investigate whether SICI evaluated with AP and PA conditioning stimuli (CS PA and CS AP ) activate different inhibitory pathways. SICI was always assessed using a PA-oriented test stimulus (TS PA ). Methods: Using two superimposed TMS coils, CS PA and CS AP were applied at interstimulus intervals (ISI) of 1e5 ms before a TS PA , and at a range of different intensities. Using a triple stimulation design, we then tested whether SICI at ISI of 3 ms using opposite directions of CS (SICI CSPA3 and SICI CSAP3 ) interacted differently with three other forms of inhibition, including SICI at ISI of 2 ms (SICI CSPA2 ), cerebellum-motor cortex inhibition (CBI 5 ms) and short-latency afferent inhibition (SAI 22 ms). Finally, we compared the effect of tonic and phasic voluntary contraction on SICI CSPA3 and SICI CSAP3 . Results: CS AP produced little SICI at ISIs ¼ 1 and 2 ms. However, at ISI ¼ 3 ms, both CS AP and CS PA were equally effective at the same percent of maximum stimulator output. Despite this apparent similarity, combining SICI CSPA3 or SICI CSAP3 with other forms of inhibition led to quite different results: SICI CSPA3 interacted in complex ways with CBI, SAI and SICI CSPA2 , whereas the effect of SICI CSAP3 appeared to be quite independent of them. Although SICI CSPA and SICI CSAP were both reduced by the same amount during voluntary tonic contraction compared with rest, in a simple reaction time task SICI CSAP was disinhibited much earlier following the imperative signal than SICI CSPA . Conclusions: SICI CSPA appears to activate a different inhibitory pathway to that activated by SICI CSAP . The difference is behaviourally relevant since the pathways are controlled differently during volitional contraction. The results may explain some previous pathological data and open the possibility of testing whether these pathways are differentially recruited in a range of tasks.
Dystonia is a hyperkinetic movement disorder characterized by abnormal movement or posture caused by excessive muscle contraction. Because of its wide clinical spectrum, dystonia is often underdiagnosed or misdiagnosed. In clinical practice, dystonia could often present in association with other movement disorders. An accurate physical examination is essential to describe the correct phenomenology. To help clinicians reaching the proper diagnosis, several classifications of dystonia have been proposed. The current classification consists of axis I, clinical characteristics, and axis II, etiology. Through the application of this classification system, movement disorder specialists could attempt to correctly characterize dystonia and guide patients to the most effective treatment. The aim of this article is to describe the phenomenological spectrum of dystonia, the last approved dystonia classification, and new emerging knowledge.
Corticospinal volleys evoked by transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) consist of high-frequency bursts (≈667 and ≈333 Hz). However, intracortical circuits producing such corticospinal high-frequency bursts are unknown. We here investigated whether neurons activated by single TMS pulses over M1 are resonant to high-frequency oscillations, using a combined transcranial alternating current stimulation (tACS)-TMS approach. We applied 667, 333 Hz or sham-tACS and, concurrently, we delivered six single-pulse TMS protocols using monophasic or biphasic pulses, different stimulation intensities, muscular states, types and orientations of coils. We recorded motor evoked potentials (MEPs) before, during and after tACS. 333 Hz tACS facilitated MEPs evoked by biphasic TMS through a figure-of-eight coil at active motor threshold (AMT), and by monophasic TMS with anteriorto-posterior-induced current in the brain. 333 Hz tACS also facilitated MEPs evoked by monophasic TMS through a circular coil at AMT, an effect that weakly persisted after the stimulation. 667 Hz tACS had no effects. 333 Hz, but not 667 Hz, tACS may have reinforced the synchronization of specific neurons to high-frequency oscillations enhancing this activity, and facilitating MEPs. Our findings suggest that different bursting modes of corticospinal neurons are produced by separate circuits with different oscillatory properties. Corticospinal neurons (CSNs) of the mammalian brain show a high frequency (≈667 Hz) burst of activity in response to transcranial electric (TES) and magnetic (TMS) stimulation. These stereotyped bursts of activity can be recorded from the surface of the high cervical cord and reflect the spiking of a large number of corticospinal axons 1-5. Recently, Maier et al. 6 recorded the responses of single corticospinal axons together with volleys from the surface of the cervical cord after intracortical stimulation in monkey and showed that individual axons fire repetitively at the high frequency revealed by surface recordings, thus demonstrating that bursts originate from the repetitive synchronous discharge of CSNs. They also found that while most of the corticospinal axons discharged at around 600 Hz, there were other axons responding at lower frequencies 6. In humans, bursts of corticospinal activity with different frequencies can be recorded by cervical epidural electrodes after TMS over the motor cortex 5. This descending bursting activity is influenced by the direction of the current flowing across the central sulcus. The more commonly used posterior-to-anterior (PA)-induced current in the brain (perpendicular to the central sulcus) preferentially evokes the 667 Hz repetitive discharge. However, when the orientation of the induced current is reversed (anterior-to-posterior in the brain; AP) or when stimulation is performed using a biphasic TMS that combines sequentially both directions of stimulation (a PA induced current followed by an AP induced current), the output changes with less synchronized vol...
In PD, chronic pain degrades response to Laser-PAS through abnormal pain-motor integration.
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