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Background: Electroconvulsive therapy (ECT) is the most effective treatment for treatment-resistant depression (TRD), especially for acute suicidal ideation, but the associated cognitive adverse effects and negative stigma limit its use. Another seizure therapy under development is magnetic seizure therapy (MST), which could potentially overcome the restrictions associated with ECT with similar efficacy. The neurophysiological targets and mechanisms of seizure therapy, however, remain poorly understood., Methods/design: This neurophysiological study protocol is published as a companion to the overall Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST) protocol that describes our two-site, double-blind, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. Our aim for the neurophysiological component of the study is to evaluate two biomarkers, one to predict remission of suicidal ideation (primary outcome) and the other to predict cognitive impairment (secondary outcome). Suicidal ideation will be assessed through cortical inhibition, which according to our preliminary studies, correlates with remission of suicidal ideation. Cortical inhibition will be measured with simultaneous transcranial magnetic stimulation (TMS) and electroencephalography (EEG), TMS-EEG, which measures TMS-evoked EEG activity. Cognitive adverse effects associated with seizure therapy, on the contrary, will be evaluated via multiscale entropy analysis reflecting the complexity of ongoing resting-state EEG activity., Discussion: ECT and MST are known to influence cortical inhibition associated with depression, suicidal ideation severity, and clinical outcome. Therefore, evaluating cortical inhibition and brain temporal dynamics will help understand the pathophysiology of depression and suicidal ideation and define new biological targets that could aid clinicians in diagnosing and selecting treatments. Resting-state EEG complexity was previously associated with the degree of cognitive side effects after a seizure therapy. This neurophysiological metric may help clinicians assess the risk for adverse effects caused by these useful and effective treatments., Trial Registration: ClinicalTrials.gov NCT03191058 . Registered on June 19, 2017., (© 2021. The Author(s).)

Despite the importance of the developing cerebellum on cognition, the associations between physical fitness and cerebellar volume in adolescents remain unclear. We explored the associations of physical fitness with gray matter (GM) volume of VI, VIIb and Crus I & II, which are cerebellar lobules related to cognition, in 40 (22 females; 17.9 ± 0.8 year‐old) adolescents, and whether the associations were sex‐specific. Peak oxygen uptake (V̇O2peak) and power were assessed by maximal ramp test on a cycle ergometer, muscular strength with standing long jump (SLJ), speed‐agility with the shuttle‐run test (SRT), coordination with the Box and Block Test (BBT) and neuromuscular performance index (NPI) as the sum of SLJ, BBT and SRT z‐scores. Body composition was measured using a dual‐energy X‐ray absorptiometry. Cerebellar volumes were assessed by magnetic resonance imaging. V̇O2peak relative to lean mass was inversely associated with the GM volume of the cerebellum (standardized regression coefficient (β) = −0.038, 95% confidence interval (CI) ‐0.075 to 0.001, p = 0.044). Cumulative NPI was positively associated with the GM volume of Crus I (β = 0.362, 95% CI 0.045 to 0.679, p = 0.027). In females, better performance in SRT was associated with a larger GM volume of Crus I (β = −0.373, 95% CI ‐0.760 to −0.028, p = 0.036). In males, cumulative NPI was inversely associated with the GM volume of Crus II (β = −0.793, 95% CI ‐1.579 to −0.008 p = 0.048). Other associations were nonsignificant. In conclusion, cardiorespiratory fitness, neuromuscular performance and speed‐agility were associated with cerebellar GM volume, and the strength and direction of associations were sex‐specific. [ABSTRACT FROM AUTHOR]

Loud sounds have been demonstrated to increase motor cortex excitability when transcranial magnetic stimulation (TMS) is synchronized with auditory evoked N100 potential measured from electroencephalography (EEG). The N100 potential is generated by an afferent response to sound onset and feature analysis, and upon novel sound it is also related to the arousal reaction. The arousal reaction is known to originate from the ascending reticular activating system of the brain stem and to modulate neuronal activity throughout the central nervous system. In this study we investigated the difference in motor evoked potentials (MEPs) when deviant and novelty stimuli were randomly interspersed in a train of standard tones. Twelve healthy subjects participated in this study. Three types of sound stimuli were used: 1) standard stimuli (800 Hz), 2) deviant stimuli (560 Hz), and 3) novelty stimuli (12 different sounds). In each stimulus sequence 600 stimuli were given. Of these, 90 were deviant stimuli randomly placed between the standard stimuli. Each of 12 novel sounds was presented once in pseudorandomized order. TMS was randomly mixed with the sound stimuli so that it was either synchronized with the individual N100 or trailed the sound onset by 200 ms. All sounds elicited an increase in motor cortex excitability. The type of sound had no significant effect. We also demonstrated that TMS timed at 200-ms intervals caused a significant increment of MEPs. This contradicted our hypothesis that MEP amplitudes to TMS synchronized with N100 would be greater than those to TMS at 200 ms after a sound and remains unexplained. [ABSTRACT FROM AUTHOR]

Repetition suppression (RS) is evident as a weakened response to repeated stimuli after the initial response. RS has been demonstrated in motor-evoked potentials (MEPs) induced with transcranial magnetic stimulation (TMS). Here, we investigated the effect of inter-train interval (ITI) on the induction of RS of MEPs with the attempt to optimize the investigative protocols. Trains of TMS pulses, targeted to the primary motor cortex by neuronavigation, were applied at a stimulation intensity of 120% of the resting motor threshold. The stimulus trains included either four or twenty pulses with an inter-stimulus interval (ISI) of 1 s. The ITI was here defined as the interval between the last pulse in a train and the first pulse in the next train; the ITIs used here were 1, 3, 4, 6, 7, 12, and 17 s. RS was observed with all ITIs except with the ITI of 1 s, in which the ITI was equal to ISI. RS was more pronounced with longer ITIs. Shorter ITIs may not allow sufficient time for a return to baseline. RS may reflect a startle-like response to the first pulse of a train followed by habituation. Longer ITIs may allow more recovery time and in turn demonstrate greater RS. Our results indicate that RS can be studied with confidence at relatively short ITIs of 6 s and above. [ABSTRACT FROM AUTHOR]

Background Transcranial magnetic stimulation (TMS) can evaluate cortical excitability and integrity of motor pathways via TMS-induced responses. The responses are affected by the orientation of the stimulated neurons with respect to the direction of the TMS-induced electric field. Therefore, besides being a functional imaging tool, TMS may potentially assess the local structural properties. Yet, TMS has not been used for this purpose. New method A novel principle to evaluate the relation between function and structure of the motor cortex is presented. This functional anisotropy is evaluated by an anisotropy index (AI), based on motor evoked potential amplitudes induced with different TMS coil orientations, i.e. different electric field directions at a cortical target. To compare the AI with anatomical anisotropy in an explorative manner, diffusion tensor imaging-derived fractional anisotropy (FA) was estimated at different depths near the stimulation site. Results AI correlated inversely with cortical excitability through the TMS-induced electric field at motor threshold level. Further, there was a trend of negative correlation between AI and FA. Comparison with existing methods None of the existing methods alone can detect the relationship between direct motor cortex activation and local neuronal structure. Conclusions The AI appears to provide information on the functional neuronal anisotropy of the motor cortex by coupling neurophysiology and neuroanatomy within the stimulated cortical region. The AI could prove useful in the evaluation of neurological disorders and traumas involving concurrent structural and functional changes in the motor cortex. Further studies on patients are needed to confirm the usability of AI. [ABSTRACT FROM AUTHOR]

Highlights: [•] Transcranial magnetic stimulation induced silent period (cSP) is commonly analysed manually. [•] A new automated routine for cSP analysis was compared with manually analysed cSPs. [•] Data from a large-population of healthy subjects were reanalysed by two of the authors. [•] Inter-examiner effect in cSP analysis was found quite large. [•] Automated routine was found valid and at least as reliable as the manual analysis. [Copyright &y& Elsevier]

Objectives Unverricht-Lundborg disease, or progressive myoclonus epilepsy type 1 (EPM1), affects cortical excitability and inhibition, and neuroanatomy of the thalamocortical system. Stimulus sensitive myoclonus with potentially disabling features associates with EPM1. Our objective was to assess neurophysiological adaptation in EPM1 to further understand the role of the impaired thalamocortical system in the characteristic features of the disease. Methods Eight EPM1 patients and 10 controls were studied using navigated transcranial magnetic stimulation (nTMS). We studied adaptation of motor cortex to excitatory external stimuli using nTMS with repetition suppression (RS) study-protocol adapted from our previous study [1] . Results We found that the reactivity and adaptation to external stimuli was highly abnormal in EPM1 patients compared to healthy controls. EPM1 group exhibited no RS effect ( F = 1.07, p = 0.385), while such effect was observed in controls ( F = 53.01, p < 0.001 ). In controls, the RS effect was seen as 50–55% reduction in motor evoked potentials of the right hand after the first stimulus in RS stimulus protocol. Conclusions Neural processing of stimuli received by the motor cortex is severely impaired in EPM1. This may be due to anatomic changes seen in the thalamocortical system, potentially impairing connective control between the thalamic nuclei and the cortex. Significance The abnormal adaption to external stimuli observed in the present study may contribute to the expression of the EPM1’s motor symptoms. This study helps to further understand the neurophysiological appearance of EPM1 in common neural functions. [ABSTRACT FROM AUTHOR]