Effects of transcranial magnetic stimulation on the human brain recorded with intracranial electrocorticography.

Transcranial magnetic stimulation (TMS) is increasingly used as a noninvasive technique for neuromodulation in research and clinical applications, yet its mechanisms are not well understood. Here, we present the neurophysiological effects of TMS using intracranial electrocorticography (iEEG) in neurosurgical patients. We first evaluated safety in a gel-based phantom. We then performed TMS-iEEG in 22 neurosurgical participants with no adverse events. We next evaluated intracranial responses to single pulses of TMS to the dorsolateral prefrontal cortex (dlPFC) (N = 10, 1414 electrodes). We demonstrate that TMS is capable of inducing evoked potentials both locally within the dlPFC and in downstream regions functionally connected to the dlPFC, including the anterior cingulate and insular cortex. These downstream effects were not observed when stimulating other distant brain regions. Intracranial dlPFC electrical stimulation had similar timing and downstream effects as TMS. These findings support the safety and promise of TMS-iEEG in humans to examine local and network-level effects of TMS with higher spatiotemporal resolution than currently available methods.

Large-scale lesion symptom mapping of depression identifies brain regions for risk and resilience.

Understanding neural circuits that support mood is a central goal of affective neuroscience, and improved understanding of the anatomy could inform more targeted interventions in mood disorders. Lesion studies provide a method of inferring the anatomical sites causally related to specific functions, including mood. Here, we performed a large-scale study evaluating the location of acquired, focal brain lesions in relation to symptoms of depression. Five hundred and twenty-six individuals participated in the study across two sites (356 male, average age 52.4 ± 14.5 years). Each subject had a focal brain lesion identified on structural imaging and an assessment of depression using the Beck Depression Inventory-II, both obtained in the chronic period post-lesion (>3 months). Multivariate lesion-symptom mapping was performed to identify lesion sites associated with higher or lower depression symptom burden, which we refer to as 'risk' versus 'resilience' regions. The brain networks and white matter tracts associated with peak regional findings were identified using functional and structural lesion network mapping, respectively. Lesion-symptom mapping identified brain regions significantly associated with both higher and lower depression severity (r = 0.11; P = 0.01). Peak 'risk' regions include the bilateral anterior insula, bilateral dorsolateral prefrontal cortex and left dorsomedial prefrontal cortex. Functional lesion network mapping demonstrated that these 'risk' regions localized to nodes of the salience network. Peak 'resilience' regions include the right orbitofrontal cortex, right medial prefrontal cortex and right inferolateral temporal cortex, nodes of the default mode network. Structural lesion network mapping implicated dorsal prefrontal white matter tracts as 'risk' tracts and ventral prefrontal white matter tracts as 'resilience' tracts, although the structural lesion network mapping findings did not survive correction for multiple comparisons. Taken together, these results demonstrate that lesions to specific nodes of the salience network and default mode network are associated with greater risk versus resiliency for depression symptoms in the setting of focal brain lesions.

The Neuropsychiatric Approach to the Assessment of Patients in Neurology.

Neuropsychiatry is a clinical neuroscience specialty focused on the evaluation and treatment of patients who present with symptoms at the intersection of neurology and psychiatry. Neuropsychiatrists assess and manage the cognitive, affective, behavioral, and perceptual manifestations of disorders of the central nervous system. Although fellowship training in behavioral neurology-neuropsychiatry exists in the United States and several other countries internationally, the need for neuropsychiatric expertise greatly outweighs the number of specialists in practice or training. This article serves as a primer for both neurologists and psychiatrists seeking to improve or refresh their knowledge of the neuropsychiatric assessment, including detailing aspects of the history-taking, physical exam, psychometric testing, and associated diagnostic work-up. In doing so, we urge the next generation of neurologists and psychiatrists to take on both the opportunity and challenge to work at the intersection of both clinical neuroscience specialties using an integrated neuropsychiatric perspective.

National Network of Depression Centers' Recommendations on Harmonizing Clinical Documentation of Electroconvulsive Therapy.

ABSTRACT: Electroconvulsive therapy (ECT) is a highly therapeutic and cost-effective treatment for severe and/or treatment-resistant major depression. However, because of the varied clinical practices, there is a great deal of heterogeneity in how ECT is delivered and documented. This represents both an opportunity to study how differences in implementation influence clinical outcomes and a challenge for carrying out coordinated quality improvement and research efforts across multiple ECT centers. The National Network of Depression Centers, a consortium of 26+ US academic medical centers of excellence providing care for patients with mood disorders, formed a task group with the goals of promoting best clinical practices for the delivery of ECT and to facilitate large-scale, multisite quality improvement and research to advance more effective and safe use of this treatment modality. The National Network of Depression Centers Task Group on ECT set out to define best practices for harmonizing the clinical documentation of ECT across treatment centers to promote clinical interoperability and facilitate a nationwide collaboration that would enable multisite quality improvement and longitudinal research in real-world settings. This article reports on the work of this effort. It focuses on the use of ECT for major depressive disorder, which accounts for the majority of ECT referrals in most countries. However, most of the recommendations on clinical documentation proposed herein will be applicable to the use of ECT for any of its indications.

Developing Precision Invasive Neuromodulation for Psychiatry.

Psychiatric conditions are common and often disabling. Although great strides have been made in alleviating symptoms with pharmacotherapy and psychotherapeutic approaches, many patients continue to have severe disease burden despite the best therapies available. One of the pervasive challenges to improving treatment is that present diagnostic and therapeutic strategies lag behind our modern conceptualization of the pathophysiology of these disorders. Psychiatric symptoms manifest through activity in specific neural circuits; thus, therapies capable of modulating these circuits are attractive. The investigators reviewed recent advances that facilitate treating medically refractory psychiatric disorders with intracranial neuromodulation in a way that intervenes more directly with the underlying pathophysiology. Specifically, they reviewed the prospects for using intracranial multielectrode arrays to record brain activity with high spatiotemporal resolution and identify circuit-level electrophysiological correlates of symptoms. A causal relationship of circuit electrophysiology to symptoms could then be established by modulating the circuits to disrupt the symptoms. Personalized therapeutic neuromodulation strategies can then proceed in a rational manner with stimulation protocols informed by the underlying circuit-based pathophysiology of the most bothersome symptoms. This strategy would enhance current methods in neurotherapeutics by identifying individualized anatomical targets with symptom-specific precision, circumventing many of the limitations inherent in modern psychiatric nosology and treatment.

Cerebellar Theta Frequency Transcranial Pulsed Stimulation Increases Frontal Theta Oscillations in Patients with Schizophrenia.

Cognitive dysfunction is a pervasive and disabling aspect of schizophrenia without adequate treatments. A recognized correlate to cognitive dysfunction in schizophrenia is attenuated frontal theta oscillations. Neuromodulation to normalize these frontal rhythms represents a potential novel therapeutic strategy. Here, we evaluate whether noninvasive neuromodulation of the cerebellum in patients with schizophrenia can enhance frontal theta oscillations, with the future goal of targeting the cerebellum as a possible therapy for cognitive dysfunction in schizophrenia. We stimulated the midline cerebellum using transcranial pulsed current stimulation (tPCS), a noninvasive transcranial direct current that can be delivered in a frequency-specific manner. A single 20-min session of theta frequency stimulation was delivered in nine patients with schizophrenia (cathode on right shoulder). Delta frequency tPCS was also delivered as a control to evaluate for frequency-specific effects. EEG signals from midfrontal electrode Cz were analyzed before and after cerebellar tPCS while patients estimated the passage of 3- and 12-s intervals. Theta oscillations were significantly larger following theta frequency cerebellar tPCS in the midfrontal region, which was not seen with delta frequency stimulation. As previously reported, patients with schizophrenia showed a baseline reduction in accuracy estimating 3- and 12-s intervals relative to control subjects, which did not significantly improve following a single-session theta or delta frequency cerebellar tPCS. These preliminary results suggest that single-session theta frequency cerebellar tPCS may modulate task-related oscillatory activity in the frontal cortex in a frequency-specific manner. These preliminary findings warrant further investigation to evaluate whether multiple sessions delivered daily may have an impact on cognitive performance and have therapeutic implications for schizophrenia.

Individualized Connectome-Targeted Transcranial Magnetic Stimulation for Neuropsychiatric Sequelae of Repetitive Traumatic Brain Injury in a Retired NFL Player.

OBJECTIVE: The recent advent of individualized resting-state network mapping (RSNM) has revealed substantial interindividual variability in anatomical localization of brain networks identified by using resting-state functional MRI (rsfMRI). RSNM enables personalized targeting of focal neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS). rTMS is believed to exert antidepressant efficacy by modulating connectivity between the stimulation site, the default mode network (DMN), and the subgenual anterior cingulate cortex (sgACC). Personalized rTMS may be particularly useful after repetitive traumatic brain injury (TBI), which is associated with neurodegenerative tauopathy in medial temporal limbic structures. These degenerative changes are believed to be related to treatment-resistant neurobehavioral disturbances observed in many retired athletes. METHODS: The authors describe a case in which RSNM was successfully used to target rTMS to treat these neuropsychiatric disturbances in a retired NFL defensive lineman whose symptoms were not responsive to conventional treatments. RSNM was used to identify left-right dorsolateral prefrontal rTMS targets with maximal difference between dorsal attention network and DMN correlations. These targets were spatially distinct from those identified by prior methods. Twenty sessions of left-sided excitatory and right-sided inhibitory rTMS were administered at these targets. RESULTS: Treatment led to improvement in Montgomery-Åsberg Depression Rating Scale (72%), cognitive testing, and headache scales scores. Compared with healthy individuals and subjects with TBI-associated depression, baseline rsfMRI revealed substantially elevated DMN connectivity with the medial temporal lobe (MTL). Serial rsfMRI scans revealed gradual improvement in MTL-DMN connectivity and stimulation site connectivity with sgACC. CONCLUSIONS: These results highlight the possibility of individualized neuromodulation and biomarker-based monitoring for neuropsychiatric sequelae of repetitive TBI.

Neurostimulation Therapies.

Depression is one of the most disabling conditions in the world. In many cases patients continue to suffer with depressive disorders despite a series of adequate trials of medication and psychotherapy. Neuromodulation treatments offer a qualitatively different modality of treatment that can frequently prove efficacious in these treatment-refractory patients. The field of neuromodulation focuses on the use of electrical/electromagnetic energy, both invasively and noninvasively, to interface with and ultimately alter activity within the human brain for therapeutic purposes. These treatments provide another set of options to offer patients when clinically indicated, and knowledge of their safety, risks and benefits, and appropriate clinical application is essential for modern psychiatrists and other mental health professionals. Although neuromodulation techniques hold tremendous promise, only three such treatments are currently approved by the United States Food and Drug Administration (FDA) for the treatment of major depressive disorder: electroconvulsive therapy (ECT), vagus nerve stimulation (VNS), and repetitive transcranial magnetic stimulation (rTMS). Additionally, numerous other neurostimulation modalities (deep brain stimulation [DBS], magnetic seizure therapy [MST], transcranial electric stimulation [tES], and trigeminal nerve stimulation [TNS]), though currently experimental, show considerable therapeutic promise. Researchers are actively looking for ways to optimize outcomes and clinical benefits by making neuromodulation treatments safer, more efficacious, and more durable.

Crossover to Bilateral Repetitive Transcranial Magnetic Stimulation: A Potential Strategy When Patients Are Not Responding to Unilateral Left-Sided High-Frequency Repetitive Transcranial Magnetic Stimulation.

Clinical trials using left-sided repetitive transcranial magnetic stimulation (rTMS) report remission rates of 14% to 32.6%. A large percentage of patients would not achieve remission with standard rTMS treatment. The question of what clinicians should do when a patient is not responding to standard high-frequency (HF) left-sided rTMS remains unanswered. This prospective case series examines whether crossover to bilateral stimulation enhances antidepressant outcomes in patients not responding to unilateral rTMS. Patients in a major depressive episode received an rTMS clinical protocol of 4 to 6 weeks' duration. Stimulation began with HF rTMS (10 Hz) over the left dorsolateral prefrontal cortex (range, 3000-5000 pulses per session). A total of 17 patients without sufficient clinical improvement early in their rTMS course received 1-Hz rTMS (range, 600-1200 pps) over the right dorsolateral prefrontal cortex (added to the HF left-sided stimulation). Hamilton Depression Rating Scale scores decreased from 13.9 ± 3.9 (mean ± SD) from the start of augmentation to 12.2 ± 5.8 at the end of acute treatment, a 1.7-point change, Cohen d effect size = -0.35, 95% confidence interval, -1.01 to - 0.34, suggesting improvement. Remission rate in this sample was 24% (4/17). This case series indicates that crossover to bilateral stimulation is a feasible and potentially effective strategy when patients are not improving with standard rTMS. A randomized controlled trial comparing crossover versus standard rTMS is needed to determine the efficacy of this paradigm.

Noninvasive Brain Stimulation: Challenges and Opportunities for a New Clinical Specialty.

Noninvasive brain stimulation refers to a set of technologies and techniques with which to modulate the excitability of the brain via transcranial stimulation. Two major modalities of noninvasive brain stimulation are transcranial magnetic stimulation (TMS) and transcranial current stimulation. Six TMS devices now have approved uses by the U.S. Food and Drug Administration and are used in clinical practice: five for treating medication refractory depression and the sixth for presurgical mapping of motor and speech areas. Several large, multisite clinical trials are currently underway that aim to expand the number of clinical applications of noninvasive brain stimulation in a way that could affect multiple clinical specialties in the coming years, including psychiatry, neurology, pediatrics, neurosurgery, physical therapy, and physical medicine and rehabilitation. In this article, the authors review some of the anticipated challenges facing the incorporation of noninvasive brain stimulation into clinical practice. Specific topics include establishing efficacy, safety, economics, and education. In discussing these topics, the authors focus on the use of TMS in the treatment of medication refractory depression when possible, because this is the most widely accepted clinical indication for TMS to date. These challenges must be thoughtfully considered to realize the potential of noninvasive brain stimulation as an emerging specialty that aims to enhance the current ability to diagnose and treat disorders of the brain.

Corrigendum: Early improvement predicts clinical outcomes similarly in 10 Hz rTMS and iTBS therapy for depression.

[This corrects the article DOI: 10.3389/fpsyt.2022.863225.].

TMS provokes target-dependent intracranial rhythms across human cortical and subcortical sites.

BACKGROUND: Transcranial magnetic stimulation (TMS) is believed to alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological effects of TMS have been extensively studied with scalp electroencephalography (EEG), this approach generally evaluates low-frequency neural activity at the cortical surface. However, TMS can be safely used in patients with intracranial electrodes (iEEG), allowing for direct assessment of deeper and more localized oscillatory responses across the frequency spectrum. OBJECTIVE/HYPOTHESIS: Our study used iEEG to understand the effects of TMS on human neural activity in the spectral domain. We asked (1) which brain regions respond to cortically-targeted TMS, and in what frequency bands, (2) whether deeper brain structures exhibit oscillatory responses, and (3) whether the neural responses to TMS reflect evoked versus induced oscillations. METHODS: We recruited 17 neurosurgical patients with indwelling electrodes and recorded neural activity while patients underwent repeated trials of single-pulse TMS at either the dorsolateral prefrontal cortex (DLPFC) or parietal cortex. iEEG signals were analyzed using spectral methods to understand the oscillatory responses to TMS. RESULTS: Stimulation to DLPFC drove widespread low-frequency increases (3-8 Hz) in frontolimbic cortices and high-frequency decreases (30-110 Hz) in frontotemporal areas, including the hippocampus. Stimulation to parietal cortex specifically provoked low-frequency responses in the medial temporal lobe. While most low-frequency activity was consistent with phase-locked evoked responses, anterior frontal regions exhibited induced theta oscillations following DLPFC stimulation. CONCLUSIONS: By combining TMS with intracranial EEG recordings, our results suggest that TMS is an effective means to perturb oscillatory neural activity in brain-wide networks, including deeper structures not directly accessed by stimulation itself.

Amygdala lesions are associated with improved mood after epilepsy surgery.

Neuroimaging studies in healthy and clinical populations strongly associate the amygdala with emotion, especially negative emotions. The consequences of surgical resection of the amygdala on mood are not well characterized. We tested the hypothesis that amygdala resection would result in mood improvement. In this study, we evaluated a cohort of 52 individuals with medial temporal lobectomy for intractable epilepsy who had resections variably involving the amygdala. All individuals achieved good post-surgical seizure control and had pre- and post-surgery mood assessment with the Beck Depression Inventory (BDI) ratings. We manually segmented the surgical resection cavities and performed multivariate lesion-symptom mapping of change in BDI. Our results showed a significant improvement in average mood ratings from pre- to post-surgery across all patients. In partial support of our hypothesis, resection of the right amygdala was significantly associated with mood improvement (r = 0.5, p = 0.008). The lesion-symptom map also showed that resection of the right hippocampus and para-hippocampal gyrus was associated with worsened post-surgical mood. Future studies could evaluate this finding prospectively in larger samples while including other neuropsychological outcome measures.

A randomized trial comparing beam F3 and 5.5 cm targeting in rTMS treatment of depression demonstrates similar effectiveness.

BACKGROUND: The Beam F3 and 5.5 cm methods are the two most common targeting strategies for localizing the left dorsolateral prefrontal cortex (DLPFC) treatment site in repetitive transcranial magnetic stimulation (rTMS) protocols. This prospective, randomized, double-blind comparative effectiveness trial assesses the clinical outcomes for these two methods in a naturalistic sample of patients with major depressive disorder (MDD) undergoing clinical rTMS treatment. METHODS: 105 adult patients with MDD (mean age = 43.2; range = 18-73; 66% female) were randomized to receive rTMS to the Beam F3 (n = 58) or 5.5 cm (n = 47) target. Between group differences from pre-to post-treatment were evaluated with the Patient Health Questionnaire-9 (PHQ-9) [primary outcome measure], Generalized Anxiety Disorder-7 (GAD-7), and clinician-administered Montgomery-Åsberg Depression Scale (MADRS). Primary treatment endpoint was completion of daily treatment series. RESULTS: Per-protocol analyses showed no statistically significant differences on any measure between the 5.5 cm and F3 groups (all p ≥ 0.50), including percent improvement (PHQ-9: 39% vs. 39%; GAD-7: 34% vs. 27%; MADRS: 40% vs. 38%), response rate (PHQ-9: 37% vs. 43%; GAD-7: 27% vs. 30%; MADRS: 43% vs. 43%), and remission rate (PHQ-9: 22% vs. 21%; MADRS: 20% vs. 19%). Post hoc analysis of anxiety symptom change while controlling for depression severity suggested more favorable anxiolytic effects with 5.5 cm targeting (p = 0.03). CONCLUSIONS: Similar antidepressant effects were observed with DLFPC rTMS using either the Beam F3 or 5.5 cm targeting method, supporting clinical equipoise in MDD patients with head circumference ≤ 60 cm. Comparison to MRI-based targeting and differential effects on anxiety symptoms require further investigation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03378570.

TMS provokes target-dependent intracranial rhythms across human cortical and subcortical sites.

Transcranial magnetic stimulation (TMS) is increasingly deployed in the treatment of neuropsychiatric illness, under the presumption that stimulation of specific cortical targets can alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological effects of TMS have been extensively studied with scalp electroencephalography (EEG), this approach is most useful for evaluating low-frequency neural activity at the cortical surface. As such, little is known about how TMS perturbs rhythmic activity among deeper structures - such as the hippocampus and amygdala - and whether stimulation can alter higher-frequency oscillations. Recent work has established that TMS can be safely used in patients with intracranial electrodes (iEEG), allowing for direct neural recordings at sufficient spatiotemporal resolution to examine localized oscillatory responses across the frequency spectrum. To that end, we recruited 17 neurosurgical patients with indwelling electrodes and recorded neural activity while patients underwent repeated trials of single-pulse TMS at several cortical sites. Stimulation to the dorsolateral prefrontal cortex (DLPFC) drove widespread low-frequency increases (3-8Hz) in frontolimbic cortices, as well as high-frequency decreases (30-110Hz) in frontotemporal areas, including the hippocampus. Stimulation to parietal cortex specifically provoked low-frequency responses in the medial temporal lobe. While most low-frequency activity was consistent with brief evoked responses, anterior frontal regions exhibited induced theta oscillations following DLPFC stimulation. Taken together, we established that non-invasive stimulation can (1) provoke a mixture of low-frequency evoked power and induced theta oscillations and (2) suppress high-frequency activity in deeper brain structures not directly accessed by stimulation itself.

Individualized precision targeting of dorsal attention and default mode networks with rTMS in traumatic brain injury-associated depression.

At the group level, antidepressant efficacy of rTMS targets is inversely related to their normative connectivity with subgenual anterior cingulate cortex (sgACC). Individualized connectivity may yield better targets, particularly in patients with neuropsychiatric disorders who may have aberrant connectivity. However, sgACC connectivity shows poor test-retest reliability at the individual level. Individualized resting-state network mapping (RSNM) can reliably map inter-individual variability in brain network organization. Thus, we sought to identify individualized RSNM-based rTMS targets that reliably target the sgACC connectivity profile. We used RSNM to identify network-based rTMS targets in 10 healthy controls and 13 individuals with traumatic brain injury-associated depression (TBI-D). These "RSNM targets" were compared with consensus structural targets and targets based on individualized anti-correlation with a group-mean-derived sgACC region ("sgACC-derived targets"). The TBI-D cohort was also randomized to receive active (n = 9) or sham (n = 4) rTMS to RSNM targets with 20 daily sessions of sequential high-frequency left-sided stimulation and low-frequency right-sided stimulation. We found that the group-mean sgACC connectivity profile was reliably estimated by individualized correlation with default mode network (DMN) and anti-correlation with dorsal attention network (DAN). Individualized RSNM targets were thus identified based on DAN anti-correlation and DMN correlation. These RSNM targets showed greater test-retest reliability than sgACC-derived targets. Counterintuitively, anti-correlation with the group-mean sgACC connectivity profile was also stronger and more reliable for RSNM-derived targets than for sgACC-derived targets. Improvement in depression after RSNM-targeted rTMS was predicted by target anti-correlation with the portions of sgACC. Active treatment also led to increased connectivity within and between the stimulation sites, the sgACC, and the DMN. Overall, these results suggest that RSNM may enable reliable individualized rTMS targeting, although further research is needed to determine whether this personalized approach can improve clinical outcomes.

Supra-second interval timing in bipolar disorder: examining the role of disorder sub-type, mood, and medication status.

Background : Widely reported by bipolar disorder (BD) patients, cognitive symptoms, including deficits in executive function, memory, attention, and timing are under-studied. Work suggests that individuals with BD show impairments in interval timing tasks, including supra-second, sub-second, and implicit motor timing compared to the neuronormative population. However, how time perception differs within individuals with BD based on BD sub-type (BDI vs II), mood, or antipsychotic medication-use has not been thoroughly investigated. The present work administered a supra-second interval timing task concurrent with electroencephalography (EEG) to patients with BD and a neuronormative comparison group. As this task is known to elicit frontal theta oscillations, signal from the frontal (Fz) lead was analyzed at rest and during the task. Results : Results suggest that individuals with BD show impairments in supra-second interval timing and reduced frontal theta power compared during the task to neuronormative controls. However, within BD sub-groups, neither time perception nor frontal theta differed in accordance with BD sub-type, mood, or antipsychotic medication use. Conclusions : his work suggests that BD sub-type, mood status or antipsychotic medication use does not alter timing profile or frontal theta activity. Together with previous work, these findings point to timing impairments in BD patients across a wide range of modalities and durations indicating that an altered ability to assess the passage of time may be a fundamental cognitive abnormality in BD.

Supra-second interval timing in bipolar disorder: examining the role of disorder sub-type, mood, and medication status.

BACKGROUND: Widely reported by bipolar disorder (BD) patients, cognitive symptoms, including deficits in executive function, memory, attention, and timing are under-studied. Work suggests that individuals with BD show impairments in interval timing tasks, including supra-second, sub-second, and implicit motor timing compared to the neuronormative population. However, how time perception differs within individuals with BD based on disorder sub-type (BDI vs II), depressed mood, or antipsychotic medication-use has not been thoroughly investigated. The present work administered a supra-second interval timing task concurrent with electroencephalography (EEG) to patients with BD and a neuronormative comparison group. As this task is known to elicit frontal theta oscillations, signal from the frontal (Fz) lead was analyzed at rest and during the task. RESULTS: Results suggest that individuals with BD show impairments in supra-second interval timing and reduced frontal theta power during the task compared to neuronormative controls. However, within BD sub-groups, neither time perception nor frontal theta differed in accordance with BD sub-type, depressed mood, or antipsychotic medication use. CONCLUSIONS: This work suggests that BD sub-type, depressed mood status or antipsychotic medication use does not alter timing profile or frontal theta activity. Together with previous work, these findings point to timing impairments in BD patients across a wide range of modalities and durations indicating that an altered ability to assess the passage of time may be a fundamental cognitive abnormality in BD.

Neuroimaging Correlates of Post-Traumatic Stress Disorder in Traumatic Brain Injury: A Systematic Review of the Literature.

Neuroimaging is widely utilized in studying traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). The risk for PTSD is greater after TBI than after non-TBI trauma, and PTSD is associated with worse outcomes after TBI. Studying the neuroimaging correlates of TBI-related PTSD may provide insights into the etiology of both conditions and help identify those TBI patients most at risk of developing persistent symptoms. The objectives of this systematic review were to examine the current literature on neuroimaging in TBI-related PTSD, summarize key findings, and highlight strengths and limitations to guide future research. A Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) compliant literature search was conducted in PubMed (MEDLINE®), PsycINFO, Embase, and Scopus databases prior to January 2022. The database query yielded 4486 articles, which were narrowed based on specified inclusion criteria to a final cohort of 16 studies, composed of 854 participants with TBI. There was no consensus regarding neuroimaging correlates of TBI-related PTSD among the included articles. A small number of studies suggest that TBI-related PTSD is associated with white matter tract changes, particularly in frontotemporal regions, as well as changes in whole-brain networks of resting-state connectivity. Future studies hoping to identify reliable neuroimaging correlates of TBI-related PTSD would benefit from ensuring consistent case definition, preferably with clinician-diagnosed TBI and PTSD, selection of comparable control groups, and attention to imaging timing post-injury. Prospective studies are needed and should aim to further differentiate predisposing factors from sequelae of TBI-related PTSD.