Towards a lifelong personalized brain health program: empowering individuals to define, pursue, and monitor meaningful outcomes.

Incorporating person-centered outcomes into clinical trials for neurodegenerative diseases has been challenging due to a deficiency in quantitative measures. Meanwhile, the integration of personally meaningful treatment targets in clinical practice remains qualitative, failing to truly inform evaluations, therapeutic interventions and longitudinal monitoring and support. We discuss the current advances and future directions in capturing individualized brain health outcomes and present an approach to integrate person-centered outcome in a scalable manner. Our approach stems from the evidence-based electronic Person-Specific Outcome Measure (ePSOM) program which prompts an individual to define personally meaningful treatment priorities and report level of confidence in managing items that matter to the individual the most (e.g., "Do I feel confident in my ability to contribute to a conversation?"). Deployed either as a single version (person only) or a dyad version (person and care partner), our proposed tool could be used as an endpoint in clinical trials, offering proof of meaningful intervention benefits and in clinical practice, by establishing an anchor for the therapeutic objectives sought by the individual.

Dysexecutive difficulty and subtle everyday functional disabilities: the digital Trail Making Test.

Background: Digital neuropsychological tests reliably capture real-time, process-based behavior that traditional paper/pencil tests cannot detect, enabling earlier detection of neurodegenerative illness. We assessed relations between informant-based subtle and mild functional decline and process-based features extracted from the digital Trail Making Test-Part B (dTMT-B). Methods: A total of 321 community-dwelling participants (56.0% female) were assessed with the Functional Activities Questionnaire (FAQ) and the dTMT-B. Three FAQ groups were constructed: FAQ = 0 (unimpaired); FAQ = 1-4 (subtle impairment); FAQ = 5-8 (mild impairment). Results: Compared to the FAQ-unimpaired group, other groups required longer pauses inside target circles (p < 0.050) and produced more total pen strokes to complete the test (p < 0.016). FAQ-subtle participants required more time to complete the entire test (p < 0.002) and drew individual lines connecting successive target circles slower (p < 0.001) than FAQ-unimpaired participants. Lines connecting successive circle targets were less straight among FAQ-mild, compared to FAQ-unimpaired participants (p < 0.044). Using stepwise nominal regression (reference group = FAQ-unimpaired), pauses inside target circles classified other participants into their respective groups (p < 0.015, respectively). Factor analysis using six dTMT-B variables (oblique rotation) yielded a two-factor solution related to impaired motor/cognitive operations (48.96% variance explained) and faster more efficient motor/cognitive operations (28.88% variance explained). Conclusion: Digital assessment technology elegantly quantifies occult, nuanced behavior not previously appreciated, operationally defines critical underlying neurocognitive constructs related to functional abilities, and yields selected process-based scores that outperform traditional paper/pencil test scores for participant classification. When brought to scale, the dTMT-B test could be a sensitive tool to detect subtle-to-mild functional deficits in emergent neurodegenerative illnesses.

Clinical classification of memory and cognitive impairment with multimodal digital biomarkers.

INTRODUCTION: Early detection of Alzheimer's disease and cognitive impairment is critical to improving the healthcare trajectories of aging adults, enabling early intervention and potential prevention of decline. METHODS: To evaluate multi-modal feature sets for assessing memory and cognitive impairment, feature selection and subsequent logistic regressions were used to identify the most salient features in classifying Rey Auditory Verbal Learning Test-determined memory impairment. RESULTS: Multimodal models incorporating graphomotor, memory, and speech and voice features provided the stronger classification performance (area under the curve = 0.83; sensitivity = 0.81, specificity = 0.80). Multimodal models were superior to all other single modality and demographics models. DISCUSSION: The current research contributes to the prevailing multimodal profile of those with cognitive impairment, suggesting that it is associated with slower speech with a particular effect on the duration, frequency, and percentage of pauses compared to normal healthy speech.

Digital Clock and Recall is superior to the Mini-Mental State Examination for the detection of mild cognitive impairment and mild dementia.

BACKGROUND: Disease-modifying treatments for Alzheimer's disease highlight the need for early detection of cognitive decline. However, at present, most primary care providers do not perform routine cognitive testing, in part due to a lack of access to practical cognitive assessments, as well as time and resources to administer and interpret the tests. Brief and sensitive digital cognitive assessments, such as the Digital Clock and Recall (DCR™), have the potential to address this need. Here, we examine the advantages of DCR over the Mini-Mental State Examination (MMSE) in detecting mild cognitive impairment (MCI) and mild dementia. METHODS: We studied 706 participants from the multisite Bio-Hermes study (age mean ± SD = 71.5 ± 6.7; 58.9% female; years of education mean ± SD = 15.4 ± 2.7; primary language English), classified as cognitively unimpaired (CU; n = 360), mild cognitive impairment (MCI; n = 234), or probable mild Alzheimer's dementia (pAD; n = 111) based on a review of medical history with selected cognitive and imaging tests. We evaluated cognitive classifications (MCI and early dementia) based on the DCR and the MMSE against cohorts based on the results of the Rey Auditory Verbal Learning Test (RAVLT), the Trail Making Test-Part B (TMT-B), and the Functional Activities Questionnaire (FAQ). We also compared the influence of demographic variables such as race (White vs. Non-White), ethnicity (Hispanic vs. Non-Hispanic), and level of education (≥ 15 years vs. < 15 years) on the DCR and MMSE scores. RESULTS: The DCR was superior on average to the MMSE in classifying mild cognitive impairment and early dementia, AUC = 0.70 for the DCR vs. 0.63 for the MMSE. DCR administration was also significantly faster (completed in less than 3 min regardless of cognitive status and age). Among 104 individuals who were labeled as "cognitively unimpaired" by the MMSE (score ≥ 28) but actually had verbal memory impairment as confirmed by the RAVLT, the DCR identified 84 (80.7%) as impaired. Moreover, the DCR score was significantly less biased by ethnicity than the MMSE, with no significant difference in the DCR score between Hispanic and non-Hispanic individuals. CONCLUSIONS: DCR outperforms the MMSE in detecting and classifying cognitive impairment-in a fraction of the time-while being not influenced by a patient's ethnicity. The results support the utility of DCR as a sensitive and efficient cognitive assessment in primary care settings. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04733989.

Shortened Motor Evoked Potential Latency in the Epileptic Hemisphere of Children With Focal Epilepsy.

PURPOSE: Motor evoked potential (MEP) amplitude and latency are acquired routinely during neuronavigated transcranial magnetic stimulation, a method of functional mapping of the motor cortex before epilepsy surgery. Although MEP amplitude is routinely used to generate a motor map, MEP latency in patients with focal epilepsy has not been studied systematically. Given that epilepsy may alter myelination, we tested whether intrinsic hand muscle MEPs obtained from the hemisphere containing a seizure focus differ in latency from MEPs collected from the opposite hemisphere. METHODS: Latencies of abductor pollicis brevis MEPs were obtained during routine motor mapping by neuronavigated transcranial magnetic stimulation in children with intractable, unihemispheric focal epilepsy. The primary motor cortex was stimulated bilaterally in all cases. Only data from patients without a lesion involving the corticospinal tract were included. We tested whether abductor pollicis brevis MEP latency varied as a function of seizure focus lateralization. RESULTS: In the 17 patients who met the inclusion criteria, the mean latency of MEPs with amplitudes in the top and bottom quartiles was shorter in the epileptic hemisphere. Interhemispheric latency difference was greater in patients with lesional epilepsy than in those with nonlesional epilepsy (0.7 ± 0.4 vs. 0.1 ± 0.6 milliseconds, P = 0.02). CONCLUSIONS: Motor evoked potential latency was shortened in the epileptic hemisphere of children with focal epilepsy.

Assessing the mechanisms of brain plasticity by transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is a non-invasive technique for focal brain stimulation based on electromagnetic induction where a fluctuating magnetic field induces a small intracranial electric current in the brain. For more than 35 years, TMS has shown promise in the diagnosis and treatment of neurological and psychiatric disorders in adults. In this review, we provide a brief introduction to the TMS technique with a focus on repetitive TMS (rTMS) protocols, particularly theta-burst stimulation (TBS), and relevant rTMS-derived metrics of brain plasticity. We then discuss the TMS-EEG technique, the use of neuronavigation in TMS, the neural substrate of TBS measures of plasticity, the inter- and intraindividual variability of those measures, effects of age and genetic factors on TBS aftereffects, and then summarize alterations of TMS-TBS measures of plasticity in major neurological and psychiatric disorders including autism spectrum disorder, schizophrenia, depression, traumatic brain injury, Alzheimer's disease, and diabetes. Finally, we discuss the translational studies of TMS-TBS measures of plasticity and their therapeutic implications.

N-acetylcysteine treatment mitigates loss of cortical parvalbumin-positive interneuron and perineuronal net integrity resulting from persistent oxidative stress in a rat TBI model.

Traumatic brain injury (TBI) increases cerebral reactive oxygen species production, which leads to continuing secondary neuronal injury after the initial insult. Cortical parvalbumin-positive interneurons (PVIs; neurons responsible for maintaining cortical inhibitory tone) are particularly vulnerable to oxidative stress and are thus disproportionately affected by TBI. Systemic N-acetylcysteine (NAC) treatment may restore cerebral glutathione equilibrium, thus preventing post-traumatic cortical PVI loss. We therefore tested whether weeks-long post-traumatic NAC treatment mitigates cortical oxidative stress, and whether such treatment preserves PVI counts and related markers of PVI integrity and prevents pathologic electroencephalographic (EEG) changes, 3 and 6 weeks after fluid percussion injury in rats. We find that moderate TBI results in persistent oxidative stress for at least 6 weeks after injury and leads to the loss of PVIs and the perineuronal net (PNN) that surrounds them as well as of per-cell parvalbumin expression. Prolonged post-TBI NAC treatment normalizes the cortical redox state, mitigates PVI and PNN loss, and - in surviving PVIs - increases per-cell parvalbumin expression. NAC treatment also preserves normal spectral EEG measures after TBI. We cautiously conclude that weeks-long NAC treatment after TBI may be a practical and well-tolerated treatment strategy to preserve cortical inhibitory tone post-TBI.

Estimating dementia risk in an African American population using the DCTclock.

The prevalence of Alzheimer's disease (AD) and related dementias (ADRD) is increasing. African Americans are twice as likely to develop dementia than other ethnic populations. Traditional cognitive screening solutions lack the sensitivity to independently identify individuals at risk for cognitive decline. The DCTclock is a 3-min AI-enabled adaptation of the well-established clock drawing test. The DCTclock can estimate dementia risk for both general cognitive impairment and the presence of AD pathology. Here we performed a retrospective analysis to assess the performance of the DCTclock to estimate future conversion to ADRD in African American participants from the Rush Alzheimer's Disease Research Center Minority Aging Research Study (MARS) and African American Clinical Core (AACORE). We assessed baseline DCTclock scores in 646 participants (baseline median age = 78.0 ± 6.4, median years of education = 14.0 ± 3.2, 78% female) and found significantly lower baseline DCTclock scores in those who received a dementia diagnosis within 3 years. We also found that 16.4% of participants with a baseline DCTclock score less than 60 were significantly more likely to develop dementia in 5 years vs. those with the highest DCTclock scores (75-100). This research demonstrates the DCTclock's ability to estimate the 5-year risk of developing dementia in an African American population. Early detection of elevated dementia risk using the DCTclock could provide patients, caregivers, and clinicians opportunities to plan and intervene early to improve cognitive health trajectories. Early detection of dementia risk can also enhance participant selection in clinical trials while reducing screening costs.

Challenges and prerequisites of risk management program in the operating rooms of Iranian hospitals: A qualitative study.

BACKGROUND: The World Health Organization (WHO) considers a safe operating room as one of the necessities of hospitals that support patients. Achieving safety in surgical operations in all countries of the world is the basic goal of healthcare centers and organizations; hence, the present study investigated the challenges and prerequisites for the implementation of an active risk management program in the operating rooms of Iranian hospitals. MATERIALS AND METHODS: This qualitative-phenomenological study was conducted in 2022. Data were collected using semi-structured interviews, targeted sampling, and the participation of 20 experts (health policy and management experts and academic officials and faculty members of universities) and executive staff (nurses and operating room technicians, doctors and surgical specialists, and officials of surgical departments) and were analyzed using the framework analysis method. RESULTS: In the resulting qualitative study, the challenges and prerequisites for active risk management in the operating room from the point of view of experts and executive staff were divided into three sub-themes. These three themes include managerial challenges and prerequisites, organizational resources (financial resources, human resources, equipment, and facilities), and cultural issues. CONCLUSION: Considering managerial prerequisites, organizational resources (financial, human, equipment, and facilities), cultural issues, and removing challenges, an active risk management program in the operating room can be implemented correctly. With the correct implementation of this program, injuries in the operating room for personnel and patients will be greatly reduced, and the satisfaction of beneficiaries and the productivity of the hospital will be greatly increased.

Discrepant expressive language lateralization in children and adolescents with epilepsy.

Neuronavigated transcranial magnetic stimulation (nTMS) has emerged as a presurgical language mapping tool distinct from the widely used functional magnetic resonance imaging (fMRI). We report fMRI and nTMS language-mapping results in 19 pediatric-epilepsy patients and compare those to definitive testing by electrical cortical stimulation, Wada test, and/or neuropsychological testing. Most discordant results occurred when fMRI found right-hemispheric language. In those cases, when nTMS showed left-hemispheric or bilateral language representation, left-hemispheric language was confirmed by definitive testing. Therefore, we propose nTMS should be considered for pediatric presurgical language-mapping when fMRI shows right-hemispheric language, with nTMS results superseding fMRI results in those scenarios.

Corticomotor plasticity as a predictor of response to high frequency transcranial magnetic stimulation treatment for major depressive disorder.

BACKGROUND: Many patients with treatment-resistant depression (TRD) respond to repetitive transcranial magnetic stimulation (rTMS) treatment. This study aimed to investigate whether modulation of corticomotor excitability by rTMS predicts response to rTMS treatment for TRD in 10 Hz and intermittent theta-burst stimulation (iTBS) protocols. METHODS: Thirteen TRD patients underwent two evaluations of corticomotor plasticity-assessed as the post-rTMS (10 Hz, iTBS) percent change (%∆) in motor evoked potential (MEP) amplitude elicited by single-pulse TMS. Following corticomotor plasticity evaluations, patients subsequently underwent a standard 6-week course of 10 Hz rTMS (4 s train, 26 s inter-train interval, 3000 total pulses, 120% of motor threshold) to the left dorsolateral prefrontal cortex. Treatment efficacy was assessed by the Beck Depression Inventory II (BDI-II) and Hamilton Depression Rating Scale (HAM-D). The change in MEPs was compared between 10 Hz and iTBS conditions and related to the change in BDI-II and HAM-D scores. RESULTS: Analyses of variance revealed that across all time-points, higher post-10 Hz MEP change was a significant predictor of greater improvement on the BDI-II (p < 0.001) and HAM-D (p = 0.022). This relationship was not observed with iTBS (p-values≥0.100). Post-hoc tests revealed the MEP change 20 min post-10 Hz was the strongest predictor of BDI-II improvement. LIMITATIONS: Cortical excitability was measured from the motor cortex, rather than the dorsolateral prefrontal cortex, where treatment is applied. The 10 Hz and iTBS protocols were performed at different intensities consistent with common practice. CONCLUSIONS: Modulation of corticomotor excitability by 10 Hz can predict response to rTMS treatment with 10 Hz rTMS.

Dynamic inhibitory control prevents salience-driven capture of visual attention.

The salience-driven selection theory is comprised of three main tenets: (a) the most salient stimulus within a monitored region of the visual field captures attention, (b) the only way to prevent salience-driven distraction is by narrowly focusing attention elsewhere, and (c) all other goal-driven processes are possible only after the most salient item has been attended. Evidence for and against this theory has been provided from two experimental paradigms. Here, event-related potentials (ERPs) recorded in a novel Go/No-Go paradigm disconfirmed all three of tenets of the theory. Participants were instructed to search cyan-item displays for a salient orientation singleton (Go trials) and to ignore randomly intermixed yellow-item displays that could also contain an orientation singleton (No-Go trials). ERP components associated with attentional orienting (posterior contralateral N2; N2pc), distractor suppression (distractor positivity; PD), and stimulus relevance (P2a) were isolated to test predictions stemming from the salience-driven selection theory. On No-Go trials, the salient oddball elicited a PD rather than an N2pc, indicating that it was suppressed, not attended. Moreover, a P2a emerged before the N2pc on Go trials, demonstrating that observers first evaluated the global color of each display and then decided to search for the oddball (Go trials) or to ignore it (No-Go trials). We conclude that goal-driven processes can lead to the prevention of salience-driven attention capture by salient visual objects within the attentional window. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Biomarkers Obtained by Transcranial Magnetic Stimulation in Neurodevelopmental Disorders.

SUMMARY: Transcranial magnetic stimulation (TMS) is a method for focal brain stimulation that is based on the principle of electromagnetic induction where small intracranial electric currents are generated by a powerful fluctuating magnetic field. Over the past three decades, TMS has shown promise in the diagnosis, monitoring, and treatment of neurological and psychiatric disorders in adults. However, the use of TMS in children has been more limited. We provide a brief introduction to the TMS technique; common TMS protocols including single-pulse TMS, paired-pulse TMS, paired associative stimulation, and repetitive TMS; and relevant TMS-derived neurophysiological measurements including resting and active motor threshold, cortical silent period, paired-pulse TMS measures of intracortical inhibition and facilitation, and plasticity metrics after repetitive TMS. We then discuss the biomarker applications of TMS in a few representative neurodevelopmental disorders including autism spectrum disorder, fragile X syndrome, attention-deficit hyperactivity disorder, Tourette syndrome, and developmental stuttering.

Large-scale analysis of interindividual variability in single and paired-pulse TMS data.

OBJECTIVE: This study brought together over 60 transcranial magnetic stimulation (TMS) researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of factors driving response variability. METHODS: Authors of previously published studies were contacted and asked to share deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to variability in response to single and paired-pulse TMS data. RESULTS: 687 healthy participant's data were pooled across 35 studies. Target muscle, pulse waveform, neuronavigation use, and TMS machine significantly predicted an individual's single-pulse TMS amplitude. Baseline motor evoked potential amplitude, motor cortex hemisphere, and motor threshold (MT) significantly predicted short-interval intracortical inhibition response. Baseline motor evoked potential amplitude, test stimulus intensity, interstimulus interval, and MT significantly predicted intracortical facilitation response. Age, hemisphere, and TMS machine significantly predicted MT. CONCLUSIONS: This large-scale analysis has identified a number of factors influencing participants' responses to single and paired-pulse TMS. We provide specific recommendations to minimise interindividual variability in single and paired-pulse TMS data. SIGNIFICANCE: This study has used large-scale analyses to give clarity to factors driving variance in TMS data. We hope that this ongoing collaborative approach will increase standardisation of methods and thus the utility of single and paired-pulse TMS.

Reproducibility of cortical response modulation induced by intermittent and continuous theta-burst stimulation of the human motor cortex.

BACKGROUND: Over the past decade, the number of experimental and clinical studies using theta-burst-stimulation (TBS) protocols of transcranial magnetic stimulation (TMS) to modulate brain activity has risen substantially. The use of TBS is motivated by the assumption that these protocols can reliably and lastingly modulate cortical excitability despite their short duration and low number of stimuli. However, this assumption, and thus the experimental validity of studies using TBS, is challenged by recent work showing large inter- and intra-subject variability in response to TBS protocols. OBJECTIVES: To date, the reproducibility of TBS effects in humans has been exclusively assessed with motor evoked potentials (MEPs), which provide an indirect and limited measure of cortical excitability. Here we combined TMS with electroencephalography (TMS-EEG) and report the first comprehensive investigation of (1) direct TMS-evoked cortical responses to intermittent (iTBS) and continuous TBS (cTBS) of the human motor cortex, and (2) reproducibility of both iTBS- and cTBS-induced cortical response modulation against a robust sham control across repeat visits with commonly used cortical responsivity metrics. RESULTS: We show that although single pulse TMS generates stable and reproducible cortical responses across visits, the modulatory effects of TBS vary substantially both between and within individuals. Overall, at the group level, most measures of the iTBS and cTBS-induced effects were not significantly different from sham-TBS. Most importantly, none of the significant TBS-induced effects observed in visit-1 were reproduced in visit-2. CONCLUSIONS: Our findings suggest that the generally accepted mechanisms of TBS-induced neuromodulation, i.e. through changes in cortical excitability, may not be accurate. Future research is needed to determine the mechanisms underlying the established therapeutic effects of TBS in neuropsychiatry and examine reproducibility of TBS-induced neuromodulation through oscillatory response dynamics.

Personality in Autism Spectrum Disorder: Associations With Face Memory Deficit and Theory of Mind.

OBJECTIVE: To examine the personality profiles of adults with autism spectrum disorder (ASD) using a standard personality assessment and to investigate the association between personality, ASD-related face memory deficit (FMD), and theory of mind (ToM). In a broader context, to examine whether there are distinct clinical phenotypes in the ASD population that have implications for personality development and treatment. METHOD: Fifty-five adults with ASD and 22 neurotypical (NT) adults underwent a battery of neuropsychological tests, including measures of personality, face memory, and ToM. We compared ASD and NT groups in terms of their Personality Assessment Inventory (PAI) profiles. Additional analyses focused on the association between specific PAI scales and FMD. Performance on the Eyes Test was compared across groups and was examined in relation to FMD. RESULTS: Adults with ASD demonstrated significant elevations on several PAI scales compared with NT adults. The presence of FMD was associated with differing PAI profiles among the ASD adults. The ASD adults with FMD scored significantly higher on scales that are sensitive to positive impression management and treatment rejection and significantly lower on scales that are sensitive to borderline personality, anxiety, depression, schizophrenia, and stress. There was a significant association between performance on the Eyes Test and FMD in the ASD group. CONCLUSION: Adults with ASD have a unique personality profile. Further, ASD adults with FMD have reduced insight into their difficulties with emotional processing and may not be as sensitive as ASD adults without FMD to the emotions of others.

Modulation of motor cortical excitability by continuous theta-burst stimulation in adults with autism spectrum disorder.

OBJECTIVE: To test whether change in motor evoked potential (ΔMEP) induced by continuous theta-burst stimulation (cTBS) of motor cortex (M1) distinguishes adults with autism spectrum disorder (ASD) from neurotypicals, and to explore the contribution of two common polymorphisms related to neuroplasticity. METHODS: 44 adult neurotypical (NT) participants (age 21-65, 34 males) and 19 adults with ASD (age 21-58, 17 males) prospectively underwent M1 cTBS. Their data were combined with previously obtained results from 35 NT and 35 ASD adults. RESULTS: ΔMEP at 15 minutes post-cTBS (T15) was a significant predictor of diagnosis (p = 0.04) in the present sample (n=63). T15 remained a significant predictor in a larger sample (n=91) and when partially imputed based on T10-T20 from a yet-greater sample (N=133). T15 also remained a significant predictor of diagnosis among brain-derived neurotrophic factor (BDNF) Met+ and apolipoprotein E (APOE) ε4- subjects (p's < 0.05), but not among Met- or ε4+ subjects (p's > 0.19). CONCLUSIONS: ΔMEP at T15 post-cTBS is a significant biomarker for adults with ASD, and its utility is modulated by BDNF and APOE polymorphisms. SIGNIFICANCE: M1 cTBS response is a physiologic biomarker for adults with ASD in large samples, and controlling for BDNF and APOE polymorphisms can improve its diagnostic utility.

EEG markers predictive of epilepsy risk in pediatric cerebral malaria - A feasibility study.

OBJECTIVE: Cerebral malaria (CM) affects 500,000 million children annually, 10% whom develop epilepsy within two years. Acute identification of biomarkers for post-CM epilepsy would allow for follow-up of the highest risk populations in resource-limited regions. We investigated the utility of electroencephalogram (EEG) and clinical metrics obtained during acute CM infection for predicting epilepsy. METHODS: We analyzed 70 EEGs recorded within 24 h of admission for CM hospitalization obtained during the Blantyre Malaria Project Epilepsy Study (2005-2007), a prospective cohort study of pediatric CM survivors. While all studies underwent spectral analyses for comparisons of mean power band frequencies, a subset of EEGs from the 10 subjects who developed epilepsy and 10 age- and sex-matched controls underwent conventional visual analysis. Findings were tested for relationships to epilepsy outcomes. RESULTS: Ten of the 70 subjects developed epilepsy. There were no significant differences between groups that were analyzed via visual EEG review; however, spectral EEG analyses revealed a significantly higher gamma-delta power ratio in CM survivors who developed epilepsy (0.23 ±â€¯0.10) than in those who did not (0.16 ±â€¯0.06), p = 0.003. Excluding potential confounders, multivariable logistic-regression analyses found relative gamma power (p = 0.003) and maximum temperature during admission (p = 0.03) significant and independent predictors of post-CM epilepsy, with area under receiver operating characteristics (AUROC) curve of 0.854. CONCLUSIONS: We found that clinical and EEG metrics acquired during acute CM presentation confer risk of post-CM epilepsy. Further studies are required to investigate the utility of gamma activity as a potential biomarker of epileptogenesis and study this process over time. Additionally, resource limitations currently prevent follow-up of all CM cases to surveil for epilepsy, and identification of acute biomarkers in this population would offer the opportunity to allocate resources more efficiently.

Large-scale analysis of interindividual variability in theta-burst stimulation data: Results from the 'Big TMS Data Collaboration'.

BACKGROUND: Many studies have attempted to identify the sources of interindividual variability in response to theta-burst stimulation (TBS). However, these studies have been limited by small sample sizes, leading to conflicting results. OBJECTIVE/HYPOTHESIS: This study brought together over 60 TMS researchers to form the 'Big TMS Data Collaboration', and create the largest known sample of individual participant TBS data to date. The goal was to enable a more comprehensive evaluation of factors driving TBS response variability. METHODS: 118 corresponding authors of TMS studies were emailed and asked to provide deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to iTBS and cTBS response variability. RESULTS: 430 healthy participants' TBS data was pooled across 22 studies (mean age = 41.9; range = 17-82; females = 217). Baseline MEP amplitude, age, target muscle, and time of day significantly predicted iTBS-induced plasticity. Baseline MEP amplitude and timepoint after TBS significantly predicted cTBS-induced plasticity. CONCLUSIONS: This is the largest known study of interindividual variability in TBS. Our findings indicate that a significant portion of variability can be attributed to the methods used to measure the modulatory effects of TBS. We provide specific methodological recommendations in order to control and mitigate these sources of variability.

Targeting Gamma-Related Pathophysiology in Autism Spectrum Disorder Using Transcranial Electrical Stimulation: Opportunities and Challenges.

A range of scalp electroencephalogram (EEG) abnormalities correlates with the core symptoms of autism spectrum disorder (ASD). Among these are alterations of brain oscillations in the gamma-frequency EEG band in adults and children with ASD, whose origin has been linked to dysfunctions of inhibitory interneuron signaling. While therapeutic interventions aimed to modulate gamma oscillations are being tested for neuropsychiatric disorders such as schizophrenia, Alzheimer's disease, and frontotemporal dementia, the prospects for therapeutic gamma modulation in ASD have not been extensively studied. Accordingly, we discuss gamma-related alterations in the setting of ASD pathophysiology, as well as potential interventions that can enhance gamma oscillations in patients with ASD. Ultimately, we argue that transcranial electrical stimulation modalities capable of entraining gamma oscillations, and thereby potentially modulating inhibitory interneuron circuitry, are promising methods to study and mitigate gamma alterations in ASD. Autism Res 2020, 13: 1051-1071. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Brain functions are mediated by various oscillatory waves of neuronal activity, ranging in amplitude and frequency. In certain neuropsychiatric disorders, such as schizophrenia and Alzheimer's disease, reduced high-frequency oscillations in the "gamma" band have been observed, and therapeutic interventions to enhance such activity are being explored. Here, we review and comment on evidence of reduced gamma activity in ASD, arguing that modalities used in other disorders may benefit individuals with ASD as well.