HighlightsS–D time constants are longer for anterior–posterior than posterior–anterior induced currents.Brief (30 μs) anterior-posterior currents evoke the longest latency MEP.Selective stimulation of neural elements may be achieved by manipulating pulse width and orientation.

Objective This work aims at flexible and practical pulse parameter control in transcranial magnetic stimulation (TMS), which is currently very limited in commercial devices. Approach We present a third generation controllable pulse parameter device (cTMS3) that uses a novel circuit topology with two energy-storage capacitors. It incorporates several implementation and functionality advantages over conventional TMS devices and other devices with advanced pulse shape control. cTMS3 generates lower internal voltage differences and is implemented with transistors with lower voltage rating than prior cTMS devices. Main results cTMS3 provides more flexible pulse shaping since the circuit topology allows four coil-voltage levels during a pulse, including approximately zero voltage. The near-zero coil voltage enables snubbing of the ringing at the end of the pulse without the need for a separate active snubber circuit. cTMS3 can generate powerful rapid pulse sequences (<10 ms inter pulse interval) by increasing the width of each subsequent pulse and utilizing the large capacitor energy storage, allowing the implementation of paradigms such as paired-pulse and quadripulse TMS with a single pulse generation circuit. cTMS3 can also generate theta (50 Hz) burst stimulation with predominantly unidirectional electric field pulses. The cTMS3 device functionality and output strength are illustrated with electrical output measurements as well as a study of the effect of pulse width and polarity on the active motor threshold in 10 healthy volunteers. Significance The cTMS3 features could extend the utility of TMS as a research, diagnostic, and therapeutic tool.

Gait disturbances represent a therapeutic challenge in Parkinson's disease (PD). To further investigate their underlying pathophysiological mechanisms, we compared brain activation related to mental imagery of gait between 15 PD patients and 15 age-matched controls using a block-design functional MRI experiment. On average, patients showed altered locomotion relatively to controls, as assessed with a standardized gait test that evaluated the severity of PD-related gait disturbances on a 25-m path. The experiment was conducted in the subjects as they rehearsed themselves walking on the same path with a gait pattern similar as that during locomotor evaluation. Imagined walking times were measured on a trial-by-trial basis as a control of behavioral performance. In both groups, mean imagined walking time was not significantly different from that measured during real gait on the path used for evaluation. The between-group comparison of the mental gait activation pattern with reference to mental imagery of standing showed hypoactivations within parieto-occipital regions, along with the left hippocampus, midline/lateral cerebellum, and presumed pedunculopontine nucleus/mesencephalic locomotor area, in patients. More specifically, the activation level of the right posterior parietal cortex located within the impaired gait-related cognitive network decreased proportionally with the severity of gait disturbances scored on the path used for gait evaluation and mental imagery. These novel findings suggest that the right posterior parietal cortex dysfunction is strongly related to the severity of gait disturbances in PD. This region may represent a target for the development of therapeutic interventions for PD-related gait disturbances.

BackgroundBenefits of cervical non-invasive vagus nerve stimulation (nVNS) devices have been shown in episodic cluster headache and preliminarily suggested in migraine, but direct evidence of vagus nerve activation using such devices is lacking. Vagal somatosensory evoked potentials (vSEPs) associated with vagal afferent activation have been reported for invasive vagus nerve stimulation (iVNS) and non-invasive auricular vagal stimulation. Here, we aimed to show and characterise vSEPs for cervical nVNS.MethodsvSEPs were recorded for 12 healthy volunteers who received nVNS over the cervical vagus nerve, bipolar electrode/DS7A stimulation over the inner tragus, and nVNS over the sternocleidomastoid (SCM) muscle. We measured peak-to-peak amplitudes (P1-N1), wave latencies, and N1 area under the curve.ResultsP1-N1 vSEPs were observed for cervical nVNS (11/12) and auricular stimulation (9/12), with latencies similar to those described previously, whereas SCM stimulation revealed only a muscle artefact with a much longer latency. A dose-response analysis showed that cervical nVNS elicited a clear vSEP response in more than 80% of the participants using an intensity of 15 V.ConclusionCervical nVNS can activate vagal afferent fibres, as evidenced by the recording of far-field vSEPs similar to those seen with iVNS and non-invasive auricular stimulation.

This study used a proportion congruency manipulation in the Stroop task in order to investigate, at the behavioral and brain substrate levels, the predictions derived from the Dual Mechanisms of Control (DMC) account of two distinct modes of cognitive control depending on the task context. Three experimental conditions were created that varied the proportion congruency: mostly incongruent (MI), mostly congruent (MC), and mostly neutral (MN) contexts. A reactive control strategy, which corresponds to transient interference resolution processes after conflict detection, was expected for the rare conflicting stimuli in the MC context, and a proactive strategy, characterized by a sustained task-relevant focus prior to the occurrence of conflict, was expected in the MI context. Results at the behavioral level supported the proactive/reactive distinction, with the replication of the classic proportion congruent effect (i.e., less interference and facilitation effects in the MI context). fMRI data only partially supported our predictions. Whereas reactive control for incongruent trials in the MC context engaged the expected fronto-parietal network including dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex, proactive control in the MI context was not associated with any sustained lateral prefrontal cortex activations, contrary to our hypothesis. Surprisingly, incongruent trials in the MI context elicited transient activation in common with incongruent trials in the MC context, especially in DLPFC, superior parietal lobe, and insula. This lack of sustained activity in MI is discussed in reference to the possible involvement of item-specific rather than list-wide mechanisms of control in the implementation of a high task-relevant focus.

Background and aimA recent sham-controlled trial showed that external trigeminal nerve stimulation (eTNS) is effective in episodic migraine (MO) prevention. However, its mechanism of action remains unknown. We performed 18-fluorodeoxyglucose positron emission tomography (FDG-PET) to evaluate brain metabolic changes before and after eTNS in episodic migraineurs.MethodsTwenty-eight individuals were recruited: 14 with MO and 20 healthy volunteers (HVs). HVs underwent a single FDG-PET, whereas patients were scanned at baseline, directly after a first prolonged session of eTNS (Cefaly®) and after three months of treatment (uncontrolled study).ResultsThe frequency of migraine attacks significantly decreased in compliant patients (N = 10). Baseline FDG-PET revealed a significant hypometabolism in fronto-temporal areas, especially in the orbitofrontal (OFC) and rostral anterior cingulate cortices (rACC) in MO patients. This hypometabolism was reduced after three months of eTNS treatment.ConclusionOur study shows that metabolic activity of OFC and rACC, which are pivotal areas in central pain and behaviour control, is decreased in migraine. This hypometabolism is reduced after three months of eTNS. eTNS might thus exert its beneficial effects via slow neuromodulation of central pain-controlling areas, a mechanism also previously reported in chronic migraine and cluster headache after percutaneous occipital nerve stimulation. However, this finding needs to be confirmed by further studies using a sham condition.

A vast body of literature exists showing functional and structural dysfunction within the brains of patients with disorders of consciousness. However, the function (fluorodeoxyglucose FDG-PET metabolism)-structure (MRI-diffusion-weighted images; DWI) relationship and how it is affected in severely brain injured patients remains ill-defined. FDG-PET and MRI-DWI in 25 severely brain injured patients (19 Disorders of Consciousness of which 7 unresponsive wakefulness syndrome, 12 minimally conscious; 6 emergence from minimally conscious state) and 25 healthy control subjects were acquired here. Default mode network (DMN) function-structure connectivity was assessed by fractional anisotropy (FA) and metabolic standardized uptake value (SUV). As expected, a profound decline in regional metabolism and white matter integrity was found in patients as compared with healthy subjects. Furthermore, a function-structure relationship was present in brain-damaged patients between functional metabolism of inferior-parietal, precuneus, and frontal regions and structural integrity of the frontal-inferiorparietal, precuneus-inferiorparietal, thalamo-inferioparietal, and thalamofrontal tracts. When focusing on patients, a stronger relationship between structural integrity of thalamoinferiorparietal tracts and thalamic metabolism in patients who have emerged from the minimally conscious state as compared with patients with disorders of consciousness was found. The latter finding Additional Supporting Information may be found in the online version of this article.

Masked prime tasks have shown that sensory information that has not been consciously perceived can nevertheless modulate behavior. The neuronal correlates of behavioral manifestations of visuomotor priming remain debated, particularly with respect to the distribution and direction (i.e. increase or decrease) of activity changes in medial frontal areas. Here, we predicted that these discrepant results could be accounted for by two automatic and unconscious processes embedded in this task: response conflict and facilitation. We used event-related functional magnetic resonance imaging (fMRI), as 24 healthy participants had to respond, as fast as possible, to a target arrow presented immediately after a subliminal masked prime arrow. There were three experimental conditions defined by the prime-target relationship: compatible, incompatible, and neutral. The classical visuomotor priming effect was reproduced, with relatively longer reaction times (RTs) in incompatible trials. Longer RTs in incompatible than in neutral trials were specifically associated with stronger blood oxygen level-dependent (BOLD) activity in a conflict-related network comprising the anterior cingulate cortex and right frontal associative areas. Motor response facilitation as shown by shorter RTs in compatible than in neutral trials was associated with reduced activation in a motor preparation network including the medial and lateral premotor cortices, as a result of the repetition suppression of the fMRI BOLD signal. The present results provide new insights into automatic and unconscious visuomotor priming processes, suggesting an involvement of either a cognitive or motor network, depending on the prime-target relationship.