Search

Background: Despite the connections and clear importance of the cerebellum in motor function, research utilizing cerebellar neuromodulation for treatment of movement disorders is still underdeveloped. Here we conduct a systematic review to investigate non-invasive neurostimulation of the cerebellum and its potential impact on motor systems and its function. Our aim is to give a general review of each neurostimulation study focusing on the cerebellum as a treatment target in the past five years at time of search, in order to update the field on current findings and inspire similar cerebellar neurostimulation research without unnecessary repetition. Methods: Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, our search included articles over the past five years that evaluated neurostimulation of the cerebellum (e.g., transcranial magnetic stimulation, transcranial direct current stimulation, and transcranial alternating current stimulation, etc.). Inclusion criteria included: (1) neurostimulation (repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS)) of the cerebellum; (2) only original articles, and (3) outcomes focused on motor functions. Exclusion criteria included: (1) neurostimulation with the goal of targeting any brain structure other than the cerebellum and (2) reviews and conference abstracts. Results: The search revealed 82 distinct articles relevant to the research question. Included are 17 articles concerning rTMS, 56 articles concerning tDCS, and 9 articles concerning tACS. The majority of the studies are controlled trials of varying types, with 79, with two case studies and one pilot study. Conclusions: Many studies showed significant effects on motor function and circuitry via non-invasive neurostimulation of the cerebellum. Common targets of cerebellar neurostimulation include visuomotor control, stroke rehabilitation for improvements in balance and coordination, and motor skill acquisition. The field is still exploring ideal parameters of neurostimulation for each disorder or function of interest. Future research areas should include the inclusion of individual anatomy, including functional connectivity, and improving stimulation selectivity.

Objectives: There is conflicting evidence regarding congruence between subjective cognitive decline and objective cognitive performance for individuals with a history of mild traumatic brain injury (mTBI). The current study investigated the congruity between subjective and objective cognition, particularly working memory, among veterans with an mTBI history, accounting for post-traumatic stress disorder (PTSD) and childhood trauma. Methods: Participants included 35 veterans with a history of mTBI sustained during deployment. Participants completed measures of subjective [i.e., Behavioral Inventory Rating of Executive Functioning (BRIEF)] and objective working memory (i.e., WAIS-IV working memory index). Congruity between subjective and objective working memory was examined using linear regression. Bonferroni-corrected correlations were run to explore relationships among working memory, psychiatric symptoms, mTBI severity, and childhood trauma. Results: Among Veterans with mTBI, subjective working memory and objective working memory performance were not significantly related (p > 0.05); however, the overall model was significant (p < 0.0001), and childhood trauma was a notable predictor (p = 0.02). Greater PTSD, depression, and sleep symptoms were significantly related to increased subjective working memory concerns, even after Bonferroni adjustments (ps < 0.0001). Better objective working memory was significantly related to a fewer number of childhood traumatic events; however, this did not sustain corrections. The majority of individuals (67%) endorsed significant working memory complaints, despite objectively performing within normal limits (within 1 SD and above). Conclusions: Subjective-objective working memory congruity among veterans with mTBI was limited. Subjective, but not objective, working memory concerns were associated with greater PTSD, depression, and sleep symptoms. Childhood trauma was a notable factor that contributed to both subjective and objective cognitive concerns. There remains clinical value in assessing subjective cognitive concerns given the strong relationships with psychiatric problems and, hence, a focus for intervention.

Abstract Background Although repetitive transcranial magnetic stimulation (‘TMS’) is becoming a gold standard treatment for pharmacoresistant depression, we lack neural target biomarkers for identifying who is most likely to respond to TMS and why. To address this gap in knowledge we evaluate neural targets defined by activation and functional connectivity of the dorsolateral prefrontal cortex-anchored cognitive control circuit, regions of the default mode network and attention circuit, and interactions with the subgenual anterior cingulate. We evaluate whether these targets and interactions between them change in a dose-dependent manner, whether changes in these neural targets correspond to changes in cognitive behavioral performance, and whether baseline and early change in neural target and cognitive behavioral performance predict subsequent symptom severity, suicidality, and quality of life outcomes. This study is designed as a pragmatic, mechanistic trial partnering with the National Clinical TMS Program of the Veteran’s Health Administration. Methods Target enrollment consists of 100 veterans with pharmacoresistant Major Depressive Disorder (MDD). All veterans will receive a clinical course of TMS and will be assessed at ‘baseline’ pre-TMS commencement, ‘first week’ after initiation of TMS (targeting five sessions) and ‘post-treatment’ at the completion of TMS (targeting 30 sessions). Veterans will be assessed using functional magnetic resonance imaging (fMRI), a cognitive behavioral performance battery, and established questionnaires. Multivariate linear mixed models will be used to assess whether neural targets change with TMS as a function of dose (Aim 1), whether extent and change of neural target relates to and predicts extent of behavioral performance (Aim 3), and whether extent of neural target change predicts improvement in symptom severity, suicidality, and quality of life (Aim 3). For all three aims, we will also assess the contribution of baseline moderators such as biological sex and age. Discussion To our knowledge, our study will be the first pragmatic, mechanistic observational trial to use fMRI imaging and cognitive-behavioral performance as biomarkers of TMS treatment response in pharmacoresistant MDD. The results of this trial will allow providers to select suitable candidates for TMS treatment and better predict treatment response by assessing circuit connectivity and cognitive-behavioral performance at baseline and during early treatment. Trial registration ClinicalTrials.gov NCT04663481 , December 5th, 2020, retrospectively registered. The first veteran was enrolled October 30th, 2020.

Abstract Objective Few studies have captured the neuropsychological profile of sporadic Creutzfeldt–Jakob disease (sCJD) with neuropsychological testing, and little is known about cognitive predictors of survival. We characterized baseline neuropsychological performance in sCJD and investigated associations with survival. Methods sCJD participants who completed the MMSE (n = 118), 61 sCJD of whom also completed a neuropsychological battery at baseline, and 135 age‐matched healthy controls, were included. Composite scores of global cognition, memory, executive functions, visuospatial, and language were derived. Cox proportional hazard models estimated survival time, controlling for age and education. Additional models adjusted for Barthel Index and PRNP codon 129 polymorphism. Results sCJD participants performed significantly worse than controls on all cognitive tasks and composites with most showing very large effect sizes. The three tests showing the largest group differences were delayed verbal recall (Hedges’g = 4.08, P