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BackgroundElectroconvulsive 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/designThis 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.DiscussionECT 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 registrationClinicalTrials.gov NCT03191058 . Registered on June 19, 2017.

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]

Background: Adolescence is a particularly vulnerable stage of development in terms of the deleterious effects of alcohol. Both lower gray matter (GM) volume and greater GABAergic activity have been associated with chronic alcohol consumption during adolescence. However, the association between these measures has not been investigated. Methods: In this exploratory study, we compared 26 young adults with a 10year history of heavy alcohol consumption with 21 controls who used little or no alcohol. Simultaneous transcranial magnetic stimulation and electroencephalography were used to assess transcranial magnetic stimulation‐evoked N45 potentials, reflecting a balance between GABAergic inhibition and N‐methyl‐D‐aspartate (NMDA) receptor‐mediated glutaminergic excitation in the brain. GM thickness was measured from magnetic resonance images and GM and N45 potentials were then correlated. Results: Cortical thickness was significantly lower in several brain regions in the heavy‐drinking group than the light‐drinking group. The N45 amplitude was significantly larger frontally in the heavy‐drinking group. Among heavy drinkers, there were several statistically significant correlations between thinner GM and larger frontal N45 amplitudes that were not detectable in the light‐drinking group. The strongest correlations were detected in the frontal and parietal lobes, especially in the left superior frontal gyrus and the left supramarginal gyrus, and in both hemispheres in the superior parietal lobes. Conclusions: These findings show that a thinner cortex and greater inhibitory neurotransmission are correlated in certain brain regions among young, long‐term heavy alcohol users. Studies are needed to explore the possible causal mechanisms underlying these effects. [ABSTRACT FROM AUTHOR]