A potential neuromodulation target for PTSD in Veterans derived from focal brain lesions.

Neuromodulation trials for PTSD have yielded mixed results, and the optimal neuroanatomical target remains unclear. We analyzed three datasets to study brain circuitry causally linked to PTSD in military Veterans. After penetrating traumatic brain injury (n=193), lesions that reduced probability of PTSD were preferentially connected to a circuit including the medial prefrontal cortex (mPFC), amygdala, and anterolateral temporal lobe (cross-validation p=0.01). In Veterans without lesions (n=180), PTSD was specifically associated with connectivity within this circuit (p<0.01). Connectivity change within this circuit correlated with PTSD improvement after transcranial magnetic stimulation (TMS) (n=20) (p<0.01), even though the circuit was not directly targeted. Finally, we directly targeted this circuit with fMRI-guided accelerated TMS, leading to rapid resolution of symptoms in a patient with severe lifelong PTSD. All results were independent of depression severity. This lesion-based PTSD circuit may serve as a neuromodulation target for Veterans with PTSD.

Brain network entropy, depression, and quality of life in people with traumatic brain injury and seizure disorders.

OBJECTIVE: Traumatic brain injury (TBI) often precedes the onset of epileptic (ES) or psychogenic nonepileptic seizures (PNES) with depression being a common comorbidity. The relationship between depression severity and quality of life (QOL) may be related to resting-state network complexity. We investigated these relationships in adults with TBI-only, TBI + ES, or TBI + PNES using Sample Entropy (SampEn), a measure of physiologic signals complexity. METHODS: Adults with TBI-only (n = 60), TBI + ES (n = 21), or TBI + PNES (n = 56) completed the Beck Depression Inventory-II (BDI-II; depression symptom severity) and QOL in Epilepsy (QOLIE-31) assessments and underwent resting-state functional magnetic resonance imaging (rs-fMRI). SampEn values derived from six resting state functional networks were calculated per participant. Effects of group, network, and group-by-network-interactions for SampEn were investigated with a mixed-effects model. We examined relationships between BDI-II, QOL, and SampEn of each of the networks. RESULTS: Groups did not differ in age, but there was a higher proportion of women with TBI + PNES (p = 0.040). TBI + ES and TBI-only groups did not differ in BDI-II or QOLIE-31 scores, while the TBI + PNES group scored worse on both measures. The fixed effects of the model revealed significant differences in SampEn values across networks (lower SampEn for the frontoparietal network compared to other networks). The likelihood ratio test for group-by-network-interactions was significant (p = 0.033). BDI-II was significantly negatively associated with Overall QOL scale scores in all groups, and significantly negatively associated with network SampEn values only in the TBI + PNES group. SIGNIFICANCE: Only TBI + PNES had significant relationships between depression symptom severity and network SampEn values indicating that the resting state network complexity is related to depression severity in this group but not in TBI + ES or TBI-only. PLAIN LANGUAGE SUMMARY: The brain has a complex network of internal connections. How well these connections work may be affected by TBI and seizures and may underlie mental health symptoms including depression; the worse the depression, the worse the quality of life. Our study compared brain organization in people with TBI, people with epilepsy after TBI, and people with nonepileptic seizures after TBI. Only people with nonepileptic seizures after TBI showed a relationship between how organized their brain connections were and how bad was their depression. We need to better understand these relationships to develop more impactful, effective treatments.

Virtual Reality and Transcranial Direct Current Stimulation for Posttraumatic Stress Disorder: A Randomized Clinical Trial.

Importance: Posttraumatic stress disorder (PTSD) is a common psychiatric disorder that is particularly difficult to treat in military veterans. Noninvasive brain stimulation has significant potential as a novel treatment to reduce PTSD symptoms. Objective: To test whether active transcranial direct current stimulation (tDCS) plus virtual reality (VR) is superior to sham tDCS plus VR for warzone-related PTSD. Design, Setting, and Participants: This double-blind randomized clinical trial was conducted among US military veterans enrolled from April 2018 to May 2023 at a secondary care Department of Veterans Affairs hospital and included 1- and 3-month follow-up visits. Participants included US military veterans with chronic PTSD and warzone-related exposure, recruited via referral and advertisement. Patients in psychiatric treatment had to be on a stable regimen for at least 6 weeks to be eligible for enrollment. Data were analyzed from May to September 2023. Intervention: Participants were randomly assigned to receive 2-mA anodal tDCS or sham tDCS targeted to the ventromedial prefrontal cortex, during six 25-minute sessions of standardized warzone VR exposure, delivered over 2 to 3 weeks. Main Outcomes and Measures: The co-primary outcomes were self-reported PTSD symptoms, measured via the PTSD checklist for DSM-5 (PCL-5), alongside quality of life. Other outcomes included psychophysiological arousal, clinician-assessed PTSD, depression, and social/occupational function. Results: A total of 54 participants (mean [SD] age, 45.7 [10.5] years; 51 [94%] males) were assessed, including 26 in the active tDCS group and 28 in the sham tDCS group. Participants in the active tDCS group reported a superior reduction in self-reported PTSD symptom severity at 1 month (t = -2.27, P = .02; Cohen d = -0.82). There were no significant differences in quality of life between active and sham tDCS groups. Active tDCS significantly accelerated psychophysiological habituation to VR events between sessions compared with sham tDCS (F5,7689.8 = 4.65; P < .001). Adverse effects were consistent with the known safety profile of the corresponding interventions. Conclusions and Relevance: These findings suggest that combined tDCS plus VR may be a promising strategy for PTSD reduction and underscore the innovative potential of these combined technologies. Trial Registration: ClinicalTrials.gov Identifier: NCT03372460.

Impulsivity and Psychiatric Diagnoses as Mediators of Suicidal Ideation and Suicide Attempts Among Veterans With Traumatic Brain Injury.

OBJECTIVE: Traumatic brain injury (TBI) is a risk factor for suicide, but questions related to mechanisms remain unanswered. Impulsivity is a risk factor for suicide and is a common sequela of TBI. The authors explored the relationships between TBI and both suicidal ideation and suicide attempts and explored whether impulsivity and comorbid psychiatric diagnoses mediate these relationships. METHODS: This cross-sectional retrospective chart review study included 164 veterans enrolled in a previous study. Sixty-nine veterans had no TBI history, and 95 had a TBI history (mild, N=44; moderate, N=13; severe, N=12; and unclear severity, N=26). To examine the associations between TBI and suicidal ideation or suicide attempts, as well as potential mediators of these relationships, chi-square tests, t tests, and logistic regression models were used. RESULTS: Unadjusted analyses indicated that veterans with TBI were more likely to report suicidal ideation; however, in analyses controlling for mediators, this relationship was no longer significant. Among veterans with TBI, suicidal ideation was related most strongly to high impulsivity (odds ratio=15.35, 95% CI=2.43-96.79), followed by depression (odds ratio=5.73, 95% CI=2.53-12.99) and posttraumatic stress disorder (odds ratio=2.57, 95% CI=1.03-6.42). TBI was not related to suicide attempts, yet suicide attempts were related to high impulsivity (odds ratio=6.95, 95% CI=1.24-38.75) and depression (odds ratio=3.89, 95% CI=1.56-9.40). CONCLUSIONS: These findings suggest that impulsivity, followed by psychiatric diagnoses, most strongly mediate the relationships between TBI and both suicidal ideation and suicide attempts. Impulsivity may be mechanistically related to, and serve as a future treatment target for, suicidality among veterans with TBI.

Effectiveness of Prefrontal Transcranial Magnetic Stimulation for Depression in Older US Military Veterans.

OBJECTIVE: While typical aging is associated with decreased cortical volume, major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) likely exacerbates this process. Cerebral atrophy leads to increased coil-to-cortex distance and when using transcranial magnetic stimulation (TMS), potentially reducing effectiveness in older adults. METHODS: Data from a large-scale quality improvement project was used. Included veterans eligible for TMS and completed TMS treatment. Age was assessed as a predictive factor of depression outcomes after TMS treatment among veterans. Secondary analyses examined the impact of age on 1) MDD response and remission and 2) MDD change within MDD-only verses comorbid MDD and PTSD groups. RESULTS: The entire sample included 471 veterans. Primary analysis revealed age as a negative predictor of depression outcomes (p = 0.019). Secondary analyses found age to be a significant predictor of remission (p = 0.004), but not clinical response. Age was not a predictive factor in depression outcomes between those with MDD-only compared to MDD+PTSD. CONCLUSIONS: Increased age predicts greater MDD symptom reduction after TMS. Although age did not predict response rates, it did predict increased rates of remission in veterans. Age did not differentially predict depression outcomes between those with or without PTSD. The sample size was sufficient to discern a difference in efficaciousness, and limitations were those inherent to registry studies in veterans. This data indicates that TMS can be an important treatment option for older individuals.

Accelerated TMS - moving quickly into the future of depression treatment.

Accelerated TMS is an emerging application of Transcranial Magnetic Stimulation (TMS) aimed to reduce treatment length and improve response time. Extant literature generally shows similar efficacy and safety profiles compared to the FDA-cleared protocols for TMS to treat major depressive disorder (MDD), yet accelerated TMS research remains at a very early stage in development. The few applied protocols have not been standardized and vary significantly across a set of core elements. In this review, we consider nine elements that include treatment parameters (i.e., frequency and inter-stimulation interval), cumulative exposure (i.e., number of treatment days, sessions per day, and pulses per session), individualized parameters (i.e., treatment target and dose), and brain state (i.e., context and concurrent treatments). Precisely which of these elements is critical and what parameters are most optimal for the treatment of MDD remains unclear. Other important considerations for accelerated TMS include durability of effect, safety profiles as doses increase over time, the possibility and advantage of individualized functional neuronavigation, use of biological readouts, and accessibility for patients most in need of the treatment. Overall, accelerated TMS appears to hold promise to reduce treatment time and achieve rapid reduction in depressive symptoms, but at this time significant work remains to be done. Rigorous clinical trials combining clinical outcomes and neuroscientific measures such as electroencephalogram, magnetic resonance imaging and e-field modeling are needed to define the future of accelerated TMS for MDD.

Thalamo-cortical circuits associated with trait- and state-repetitive negative thinking in major depressive disorder.

BACKGROUND: Repetitive negative thinking (RNT), often referred to as rumination in the mood disorders literature, is a symptom dimension associated with poor prognosis and suicide in major depressive disorder (MDD). Given the transdiagnostic nature of RNT, this study aimed to evaluate the hypothesis that neurobiological substrates of RNT in MDD may share the brain mechanisms underlying obsessions, particularly those involving cortico-striatal-thalamic-cortical (CSTC) circuits. METHODS: Thirty-nine individuals with MDD underwent RNT induction during fMRI. Trait-RNT was measured by the Ruminative Response Scale (RRS) and state-RNT was measured by a visual analogue scale. We employed a connectome-wide association analysis examining the association between RNT intensity with striatal and thalamic connectivity. RESULTS: A greater RRS score was associated with hyperconnectivity of the right mediodorsal thalamus with prefrontal cortex, including lateral orbitofrontal cortex, along with Wernicke's area and posterior default mode network nodes (t = 4.66-6.70). A greater state-RNT score was associated with hyperconnectivity of the right laterodorsal thalamus with bilateral primary sensory and motor cortices, supplementary motor area, and Broca's area (t = 4.51-6.57). Unexpectedly, there were no significant findings related to the striatum. CONCLUSIONS: The present results suggest RNT in MDD is subserved by abnormal connectivity between right thalamic nuclei and cortical regions involved in both visceral and higher order cognitive processing. Emerging deep-brain neuromodulation methods may be useful to establish causal relationships between dysfunction of right thalamic-cortical circuits and RNT in MDD.

Suicidal thoughts and behaviours among military veterans: protocol for a prospective, observational, neuroimaging study.

INTRODUCTION: This study's overarching goal is to examine the relationship between brain circuits and suicidal thoughts and behaviours (STBs) in a transdiagnostic sample of US military veterans. Because STBs have been linked with maladaptive decision-making and disorders linked to impulsivity, this investigation focuses on valence and inhibitory control circuits. METHODS AND ANALYSIS: In this prospective, observational study, we will collect functional MRI (fMRI), cognitive and clinical data from 136 veterans (target sample size) recruited from the Providence VA Health System (PVAHS): 68 with STBs and 68 matched controls. Behavioural data will be collected using standardised measures of STBs, psychiatric symptoms, cognition, functioning and medical history. Neuroimaging data will include structural, task and resting fMRI. We will conduct follow-up interviews and assessments at 6, 12 and 24 months post-enrolment. Primary analyses will compare data from veterans with and without STBs and will also evaluate whether activation and connectivity within circuits of valence and inhibition covary with historical and prospective patterns of suicidal ideation and behaviour. ETHICS AND DISSEMINATION: The PVAHS Institutional Review Board approved this study (2018-051). Written informed consent will be obtained from all participants. Findings from this study will be published in peer-reviewed journals and presented at local, regional, national and international conferences.Nauder Namaky, Ph.D.* nauder_namaky@brown.edu.

Retention of older veterans with serious mental illness in a clinical exercise program.

Older adults with serious mental illness (SMI) have compromised physical function that could be improved with exercise; however, retention in exercise programs is a challenge. This study was a retrospective analysis of retention for the 150 older veterans with SMI that enrolled in Gerofit, a clinical exercise program offered in the Veterans Health Administration. Chi-square and t-tests were conducted to evaluate baseline differences between those that were and were not retained at six and 12 months. Retention was 33% and better health-related quality of life and endurance were related to retention. Future work is needed to improve exercise program retention in this population.

Transcranial direct current stimulation impairs updating of avoidance-based associative learning.

Introduction: Exposure-based psychotherapies for the treatment of anxiety- and fear-based disorders rely on "corrective" associative learning. Namely the repeated confrontation with feared stimuli in the absence of negative outcomes allows the formation of new, corrected associations of safety, indicating that such stimuli no longer need to be avoided. Unfortunately, exposure-facilitated corrective learning tends to be bound by context and often poorly generalizes. One brain structure, the prefrontal cortex, is implicated in context-guided behavior and may be a relevant target for improving generalization of safety learning. Here, we tested whether inhibition of the left prefrontal cortex causally impaired updating of context-bound associations specifically or, alternatively, impaired updating of learned associations irrespective of contextual changes. Additionally, we tested whether prefrontal inhibition during corrective learning influenced subsequent generalization of associations to a novel context. Methods: In two separate experiments, participants received either 10 min of 2 mA cathodal transcranial direct current stimulation (tDCS) over EEG coordinate F3 (Experiment 1 n = 9, Experiment 2 n = 22) or sham stimulation (Experiment 1 n = 10, Experiment 2 n = 22) while previously learned associations were reversed in the same or a different context from initial learning. Next, to assess generalization of learning, participants were asked to indicate which of the previously seen images they preferred in a novel, never seen before context. Results: Results indicate that tDCS significantly impaired reversal irrespective of context in Experiment 2 only. When taking learning rate across trials into account, both experiments suggest that participants who received sham had the greatest learning rate when reversal occurred in a different context, as expected, whereas participants who received active tDCS in this condition had the lowest learning rate. However, active tDCS was associated with preferring the originally disadvantageous, but then neural stimulus after stimulus after reversal occurred in a different context in Experiment 1 only. Discussion: These results support a causal role for the left prefrontal cortex in the updating of avoidance-based associations and encourage further inquiry investigating the use of non-invasive brain stimulation on flexible updating of learned associations.

Modeling the antidepressant treatment response to transcranial magnetic stimulation using an exponential decay function.

Recovery from depression often demonstrates a nonlinear pattern of treatment response, where the largest reduction in symptoms is observed early followed by smaller improvements. This study investigated whether this exponential pattern could model the antidepressant response to repetitive transcranial magnetic stimulation (TMS). Symptom ratings from 97 patients treated with TMS for depression were collected at baseline and after every five sessions. A nonlinear mixed-effects model was constructed using an exponential decay function. This model was also applied to group-level data from several published clinical trials of TMS for treatment-resistant depression. These nonlinear models were compared to corresponding linear models. In our clinical sample, response to TMS was well modeled with the exponential decay function, yielding significant estimates for all parameters and demonstrating superior fit compared to a linear model. Similarly, when applied to multiple studies comparing TMS modalities as well as to previously identified treatment response trajectories, the exponential decay models yielded consistently better fits compared to linear models. These results demonstrate that the antidepressant response to TMS follows a nonlinear pattern of improvement that is well modeled with an exponential decay function. This modeling offers a simple and useful framework to inform clinical decisions and future studies.

Examining the neural mechanisms of rTMS: a naturalistic pilot study of acute and serial effects in pharmacoresistant depression.

Introduction: Previous studies have demonstrated the effectiveness of therapeutic repetitive transcranial magnetic stimulation (rTMS) to treat pharmacoresistant depression. Nevertheless, these trials have primarily focused on the therapeutic and neurophysiological effects of rTMS following a long-term treatment course. Identifying brain-based biomarkers of early rTMS therapeutic response remains an important unanswered question. In this pilot study, we examined the effects of rTMS on individuals with pharmacoresistant depression using a graph-based method, called Functional Cortical Networks (FCN), and serial electroencephalography (EEG). We hypothesized that changes in brain activity would occur early in treatment course. Methods: A total of 15 patients with pharmacoresistant depression underwent five rTMS sessions (5Hz over the left dorsolateral prefrontal cortex, 120%MT, up to 4,000 pulses/session). Five participants received additional rTMS treatment, up to 40 sessions. Resting EEG activity was measured at baseline and following every five sessions, using 64-channel EEG, for 10 minutes with eyes closed. An FCN model was constructed using time-varying graphs and motif synchronization. The primary outcome was acute changes in weighted-node degree. Secondary outcomes included serial FFT-based power spectral analysis and changes in depressive symptoms measured by the 9-Item Patient Health Questionnaire (PHQ-9) and the 30-item Inventory of Depressive Symptoms-Self Report (IDS-SR). Results: We found a significant acute effect over the left posterior area after five sessions, as evidenced by an increase in weighted-node degree of 37,824.59 (95% CI, 468.20 to 75,180.98) and a marginal enhancement in the left frontal region (t (14) = 2.0820, p = 0.056). One-way repeated measures ANOVA indicated a significant decrease in absolute beta power over the left prefrontal cortex (F (7, 28) = 2.37, p = 0.048) following ten rTMS sessions. Furthermore, a significant clinical improvement was observed following five rTMS sessions on both PHQ-9 (t (14) = 2.7093, p = 0.017) and IDS-SR (t (14) = 2.5278, p = 0.024) and progressed along the treatment course. Discussion: Our findings suggest that FCN models and serial EEG may contribute to a deeper understanding of mechanisms underlying rTMS treatment. Additional research is required to investigate the acute and serial effects of rTMS in pharmacoresistant depression and assess whether early EEG changes could serve as predictors of therapeutic rTMS response.

Repeatability of neurite orientation dispersion and density imaging in patients with traumatic brain injury.

BACKGROUND AND PURPOSE: The aim of this study was to assess the repeatability of neurite orientation dispersion and density imaging in healthy controls (HCs) and traumatic brain injury (TBI). METHODS: Seventeen HCs and 48 TBI patients were scanned twice over 18 weeks with diffusion imaging. Orientation dispersion (ODI), neurite density (NDI), and the fraction of isotropic diffusion (F-ISO) were quantified in regions of interest (ROIs) from a gray matter, subcortical, and white matter atlas and compared using the coefficient of variation for repeated measures (CVrep ), which quantifies the expected percent change on repeated measurement. We used a modified signed likelihood ratio test (M-SLRT) to compare the CVrep between groups in each ROI while correcting for multiple comparisons. RESULTS: NDI exhibited excellent repeatability in both groups; the only group difference was found in the fusiform gyrus, where HCs exhibited better repeatability (M-SLRT = 9.463, p = .0021). ODI also had excellent repeatability in both groups, although repeatability was significantly better in HCs in 16 cortical ROIs (p < .0022) and in the bilateral white matter and bilateral cortex (p < .0027). F-ISO exhibited relatively poor repeatability in both groups, with few group differences. CONCLUSION: Overall, the repeatability of the NDI, ODI, and F-ISO metrics over an 18-week period is acceptable for assessing the effects of behavioral or pharmacological interventions, though caution is advised when assessing F-ISO changes over time.

White Matter Changes after Neurobehavioral Therapy for Functional Seizures.

OBJECTIVE: We aimed to prospectively quantify changes in white matter morphology after neurobehavioral therapy (NBT) for functional seizures (FS) using neurite orientation dispersion and density imaging (NODDI). We hypothesized that patients with FS would exhibit white matter plasticity in the uncinate fasciculus, fornix/stria terminalis, cingulum, and corticospinal tract following NBT that would correlate with improvements in affective symptoms, postconcussive symptoms, and quality of life (QOL). METHODS: Forty-two patients with traumatic brain injury (TBI) and FS (TBI+FS) underwent NBT and provided pre-/postintervention neuroimaging and behavioral data; 47 controls with TBI without FS (TBI-only) completed the same measures but did not receive NBT. Changes in neurite density, orientation dispersion (orientation dispersion index [ODI]), and extracellular free water (FW) were compared between groups. RESULTS: Significant ODI increases in the left uncinate fasciculus in TBI+FS (mean difference = 0.017, p = 0.039) correlated with improvements in posttraumatic symptoms (r = -0.395, p = 0.013), QOL (r = 0.474, p = 0.002), emotional well-being (r = 0.524, p < 0.001), and energy (r = 0.474, p = 0.002). In TBI-only, ODI decreased (mean difference = -0.008, p = 0.047) and FW increased (mean difference = 0.011, p = 0.003) in the right cingulum. FW increases correlated with increased psychological problems (r = 0.383, p = 0.013). In TBI+FS, NBT resulted in FS decreases of 3.5 seizures per week. None of the imaging changes correlated with FS frequency. INTERPRETATION: We identified white matter changes after NBT in patients with FS that were associated with improved psychosocial functioning. NODDI could be incorporated into future mechanistic assessments of interventions in patients with FS. ANN NEUROL 2023;94:350-365.

Fronto-central resting-state 15-29 Hz transient beta events change with therapeutic transcranial magnetic stimulation for posttraumatic stress disorder and major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD) and shows promise for posttraumatic stress disorder (PTSD), yet effectiveness varies. Electroencephalography (EEG) can identify rTMS-associated brain changes. EEG oscillations are often examined using averaging approaches that mask finer time-scale dynamics. Recent advances show some brain oscillations emerge as transient increases in power, a phenomenon termed "Spectral Events," and that event characteristics correspond with cognitive functions. We applied Spectral Event analyses to identify potential EEG biomarkers of effective rTMS treatment. Resting 8-electrode EEG was collected from 23 patients with MDD and PTSD before and after 5 Hz rTMS targeting the left dorsolateral prefrontal cortex. Using an open-source toolbox ( https://github.com/jonescompneurolab/SpectralEvents ), we quantified event features and tested for treatment associated changes. Spectral Events in delta/theta (1-6 Hz), alpha (7-14 Hz), and beta (15-29 Hz) bands occurred in all patients. rTMS-induced improvement in comorbid MDD PTSD were associated with pre- to post-treatment changes in fronto-central electrode beta event features, including frontal beta event frequency spans and durations, and central beta event maxima power. Furthermore, frontal pre-treatment beta event duration correlated negatively with MDD symptom improvement. Beta events may provide new biomarkers of clinical response and advance the understanding of rTMS.

Physical Function Assessment of Older Veterans With Serious Mental Illness.

OBJECTIVE: To characterize the physical function of older veterans with serious mental illness (SMI) across endurance, strength, and mobility domains. DESIGN: Retrospective analysis of clinical performance data. SETTING: Gerofit program, a national outpatient supervised exercise program for older veterans, delivered in Veterans Health Administration sites. PARTICIPANTS: Older veterans aged 60 and older (n = 166 with SMI, n = 1,441 without SMI) enrolled across eight national Gerofit sites between 2010 and 2019. MEASUREMENTS: Performance measures of physical function covering endurance (6-minute walk test), strength (chair stands, arm curls), and mobility (10-m walk, 8-foot-up-and-go), were administered at Gerofit enrollment. Baseline data from these measures were analyzed to characterize the functional profiles of older veterans with SMI. One sample t tests were examined to compare functional performance of older veterans with SMI to age- and sex-based reference scores. Propensity score matching (1:3) and linear mixed effects models were used to evaluate differences in function between veterans with and without SMI. RESULTS: Older veterans with SMI performed worse on all measures of function (chair stands, arm curls, 10-m walk, 6-minute walk test, 8-foot-up-and-go) compared to age- and sex-based reference scores with statistically significant differences present in the male sample. Functional performance of those with SMI was also worse compared to propensity-score matched older veterans without SMI with statistically significant differences on chair stands, 6-minute walk test, and 10-m walk. CONCLUSION: Older veterans with SMI have compromised strength, mobility, and endurance. Physical function should be a core component of screening and treatment for this population.

Fronto-central resting-state 15-29Hz transient beta events change with therapeutic transcranial magnetic stimulation for posttraumatic stress disorder and major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD) and shows promise for posttraumatic stress disorder (PTSD), yet effectiveness varies. Electroencephalography (EEG) can identify rTMS-associated brain changes. EEG oscillations are often examined using averaging approaches that mask finer time-scale dynamics. Recent advances show some brain oscillations emerge as transient increases in power, a phenomenon termed "Spectral Events," and that event characteristics correspond with cognitive functions. We applied Spectral Event analyses to identify potential EEG biomarkers of effective rTMS treatment. Resting 8-electrode EEG was collected from 23 patients with MDD and PTSD before and after 5Hz rTMS targeting the left dorsolateral prefrontal cortex. Using an open-source toolbox ( https://github.com/jonescompneurolab/SpectralEvents ), we quantified event features and tested for treatment associated changes. Spectral Events in delta/theta (1-6 Hz), alpha (7-14 Hz), and beta (15-29 Hz) bands occurred in all patients. rTMS-induced improvement in comorbid MDD PTSD were associated with pre-to post-treatment changes in fronto-central electrode beta event features, including frontal beta event frequency spans and durations, and central beta event maxima power. Furthermore, frontal pre-treatment beta event duration correlated negatively with MDD symptom improvement. Beta events may provide new biomarkers of clinical response and advance the understanding of rTMS.