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Behavioral and emotional dyscontrol commonly occur following traumatic brain injury (TBI). Neuroimaging and electrophysiological correlates of dyscontrol have not been systematically summarized in the literature to date.To complete a systematic review of the literature examining neuroimaging and electrophysiological findings related to behavioral and emotional dyscontrol due to TBI.A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant literature search was conducted in PubMed (MEDLINE), PsycINFO, EMBASE, and Scopus databases prior to May 2019. The database query yielded 4392 unique articles. These articles were narrowed based on specific inclusion criteria (e.g., clear TBI definition, statistical analysis of the relationship between neuroimaging and dyscontrol).A final cohort of 24 articles resulted, comprising findings from 1552 patients with TBI. Studies included civilian (n = 12), military (n = 10), and sport (n = 2) samples with significant variation in the severity of TBI incorporated. Global and region-based structural imaging was more frequently used to study dyscontrol than functional imaging or diffusion tensor imaging. The prefrontal cortex was the most common neuroanatomical region associated with behavioral and emotional dyscontrol, followed by other frontal and temporal lobe findings.Frontal and temporal lesions are most strongly implicated in the development of postinjury dyscontrol symptoms although they are also the most frequently investigated regions of the brain for these symptom categories. Future studies can make valuable contributions to the field by (1) emphasizing consistent definitions of behavioral and emotional dyscontrol, (2) assessing premorbid dyscontrol symptoms in subjects, (3) utilizing functional or structural connectivity-based imaging techniques, or (4) restricting analyses to more focused brain regions.

Examining depression following neurological injury is useful for understanding post-lesion depression and depression more generally. The extant literature shows variability in the incidence and severity of depression post-lesion, likely due to heterogeneity in study methodology, patient samples, measures of depression, and time of assessment. Here, we aim to characterize depression symptoms and their demographic correlates in a large sample of individuals in the chronic epoch following a focal brain lesion.We sampled 492 individuals who had focal, stable brain lesions and were in the chronic epoch (≥3 months post-onset). Demographic (gender, years of education), temporal (age at lesion onset, time since lesion onset), and lesion (lesion laterality, lesion etiology, lesion volume) factors were used to predict depression symptoms measured by the Beck Depression Inventory (BDI).We found that on average, neurological patients exhibited elevated levels of depression symptoms (although not clinically significant) relative to a community sample, and the neurological patients showed higher rates of mild and moderate depression symptoms than are typical in a community sample. Gender and lesion etiology were predictive of depression symptoms, whereby women and patients with ischemic stroke had higher levels of depression symptoms.Our results suggest that depression symptom severity may be elevated following a focal brain lesion. Moreover, some individuals may be more likely to develop depression symptoms post-lesion than others. This may be mediated by individual factors such as gender and lesion etiology. The findings have important implications for the diagnosis, prognosis, and treatment of depression in neurological patients.

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.

BACKGROUND. Results reported in the existing literature have shown intermittent theta burst stimulation (iTBS) to be non-inferior to 10 Hz repetitive transcranial magnetic stimulation (rTMS) in treating major depressive disorder (MDD) when targeted at the left dorsolateral prefrontal cortex. The goal of this naturalistic observational study was to further explore potential differences between these 2 treatment modalities in treating depression in a real-world cohort. METHODS. The participants were 105 patients 18 years of age or older with a diagnosis of MDD who received standard clinical 10 Hz rTMS or iTBS treatment between 2016 and 2020. Clinical outcomes of depression treatment were assessed on the basis of changes in scores on the Patient Health Questionnaire-9 (PHQ-9) and on the Montgomery–Åsberg Depression Rating Scale (MADRS). RESULTS. Reduction in depression symptoms was measured with the PHQ-9 and MADRS depression rating scales from baseline to end of treatment, and no discernible differences in percent change, response, remission, or minimum clinically important difference (MCID) were found between the 10 Hz rTMS and iTBS treatment groups. CONCLUSIONS. Findings in an observational, real-world clinical sample showed no significant differences in outcomes between 10 Hz rTMS and iTBS targeted at the left dorsolateral prefrontal cortex in the treatment of MDD. Because of the shorter treatment time involved, the choice of iTBS may reduce hospital exposure and increase savings and the treatment capacity of clinics without sacrificing effectiveness.

Background Traumatic brain injury (TBI) can precipitate new-onset psychiatric symptoms or worsen existing psychiatric conditions. To elucidate specific mechanisms for this interaction, neuroimaging is often used to study both psychiatric conditions and TBI. This systematic review aims to synthesize the existing literature of neuroimaging findings among patients with anxiety after TBI. Methods We conducted a Preferred Reporting Items for Systematic Review and Meta-Analyses–compliant literature search via PubMed (MEDLINE), PsychINFO, EMBASE, and Scopus databases before May, 2019. We included studies that clearly defined TBI, measured syndromic anxiety as a primary outcome, and statistically analyzed the relationship between neuroimaging findings and anxiety symptoms. Results A total of 5982 articles were retrieved from the systematic search, of which 65 studied anxiety and 13 met eligibility criteria. These studies were published between 2004 and 2017, collectively analyzing 764 participants comprised of 470 patients with TBI and 294 non-TBI controls. Imaging modalities used included magnetic resonance imaging, functional magnetic resonance imaging, diffusion tensor imaging, electroencephalogram, magnetic resonance spectrometry, and magnetoencephalography. Eight of 13 studies presented at least one significant finding and together reflect a complex set of changes that lead to anxiety in the setting of TBI. The left cingulate gyrus in particular was found to be significant in 2 studies using different imaging modalities. Two studies also revealed perturbances in functional connectivity within the default mode network. Conclusions This is the first systemic review of neuroimaging changes associated with anxiety after TBI, which implicated multiple brain structures and circuits, such as the default mode network. Future research with consistent, rigorous measurements of TBI and syndromic anxiety, as well as attention to control groups, previous TBIs, and time interval between TBI and neuroimaging, are warranted. By understanding neuroimaging correlates of psychiatric symptoms, this work could inform future post-TBI screening and surveillance, preventative efforts, and early interventions to improve neuropsychiatric outcomes.

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

ObjectivesThough widely reported by patients, cognitive symptoms associated with bipolar disorder (BD), including deficits in executive function, memory, attention, and timing are under-studied. Work suggests that individuals with BD show impairments in sub-second interval timing tasks (ITT), however, results have been inconclusive regarding supra-second time perception in BD patients. Additionally, the effects of mood or medication status on time perception in BD patients are debated in the literature.MethodsTo address this, the present work administered a supra-second ITT concurrent with electroencephalographic (EEG) recordings to patients with BD and neuronormative controls. As this task is known to elicit frontal theta oscillations, which can be abnormal in psychiatric populations, signal from the Fz lead was analyzed at rest and during the task.Results & ConclusionsAs hypothesized, results suggest that individuals with BD show impairments in supra-second ITT performance compared to neuronormative controls. Frontal theta power was also reduced compared to controls during the ITT but not during rest. Finally, timing impairments remain detectible in BD patients independent of mood state and use of antipsychotic medication. This suggests that supra-second interval timing deficits are a key characteristic observed in BD. Together with previous work, these findings point to critical timing impairments in BD patients across a wide range of timing modalities and durations.

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.

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.

Background No consensus exists in the clinical transcranial magnetic stimulation (TMS) field as to the best method for targeting the left dorsolateral prefrontal cortex (DLPFC) for depression treatment. Two common targeting methods are the Beam F3 method and the 5.5 cm rule. Objective Evaluate the anatomical reliability of technician-identified DLPFC targets and obtain consensus average brain and scalp MNI152 coordinates. Methods Three trained TMS technicians performed repeated targeting using both the Beam F3 method and 5.5 cm rule in ten healthy subjects (n = 162). Average target locations were plotted on 7T structural MRIs to compare inter- and intra-rater reliability, respectively. Results (1) Beam F3 inter- and intra-rater reliability was superior to 5.5 cm targeting (p = 0.0005 and 0.0035). (2) The average Beam F3 location was 2.6±1.0 cm anterolateral to the 5.5 cm method. Conclusions Beam F3 targeting demonstrates greater precision and reliability than the 5.5 cm method and identifies a different anatomical target.

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.

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 first in-human study evaluating the 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 20 neurosurgical participants with no adverse events. Next, we evaluated brain-wide intracranial responses to single pulses of TMS to the dorsolateral prefrontal cortex (dlPFC) (N=10, 1414 electrodes). We demonstrate that TMS preferentially induces neuronal responses locally within the dlPFC at sites with higher electric field strength. Evoked responses were also noted downstream in the anterior cingulate and anterior insular cortex, regions functionally connected to the dlPFC. 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.

Background 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. Objective To identify individualized RSNM-based rTMS targets that reliably target the sgACC connectivity profile. Methods 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 (“anti-group-mean sgACC targets”). The TBI-D cohort was randomized to receive active (n=9) or sham (n=4) rTMS to RSNM targets. Results 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 then identified based on DAN anti-correlation and DMN correlation. Counterintuitively, anti-correlation with the group-mean sgACC connectivity profile was stronger and more reliable for RSNM-derived targets than for “anti-group-mean sgACC targets”. Improvement in depression after RSNM-targeted rTMS was predicted by target anti-correlation with the portions of sgACC. Active treatment led to increased connectivity within and between several relevant regions. Conclusions RSNM may enable reliable individualized rTMS targeting, although further research is needed to determine whether this personalized approach can improve clinical outcomes.

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.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.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.These results highlight the possibility of individualized neuromodulation and biomarker-based monitoring for neuropsychiatric sequelae of repetitive TBI.

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 non-invasive transcranial direct current that can be delivered in a frequency specific manner. A single 20-minute session of theta frequency stimulation was delivered in 9 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 second 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 second 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.

Smoking cessation treatment outcomes may be heavily influenced by genetic variations among smokers. Therefore, identifying specific variants that affect response to different pharmacotherapies is of major interest to the field. In the current study, we systematically review all studies published in or after the year 1990 which examined one or more gene–drug interactions for smoking cessation treatment. Out of 644 citations, 46 articles met the inclusion criteria for the systematic review. We summarize evidence on several genetic polymorphisms (CHRNA5-A3-B4, CYP2A6, DBH, CHRNA4, COMT, DRD2, DRD4 and CYP2B6) and their potential moderating pharamacotherarpy effects on patient cessation efficacy rates. These findings are promising and call for further research to demonstrate the effectiveness of genetic testing in personalizing treatment decision-making and improving outcome.

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.

Background Accurate identification of cranial midline structures is essential for many targeting techniques that use repetitive transcranial magnetic stimulation (rTMS), including the Beam F3 method used for depression treatment. Objective Evaluate whether a novel, laser-sighted device will assist with more accurate identification of the cranial midline relative to standard scalp-based measurement procedures. Methods Three trained TMS technicians performed repeated scalp-based measurements to identify the inion and vertex on five subjects (n = 54 measurements). Measurements were compared to points identified with the midline localizer device and the true midline as defined by MRI midline structures. Results Use of the midline localizer was more accurate for midline identification than technician measurement (p = 0.00025) and the ratio of localizing the midline within 5 mm was higher (78% versus 54%, p = 0.008). Conclusion Use of a laser-sighted midline localizer device can improve the accuracy of scalp measurements associated with target localization for rTMS treatment protocols.

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.

Objective To complete a systematic review of the literature examining neuroimaging findings unique to co-occurring syndromal depression in the setting of TBI. Methods A PRISMA compliant literature search was conducted in PubMed (MEDLINE), PsychINFO, EMBASE, and Scopus databases for articles published prior to April of 2022. The database query yielded 4447 unique articles. These articles were narrowed based on specific inclusion criteria (e.g., clear TBI definition, clear depression construct commenting on the syndrome of major depressive disorder, conducted empirical analyses comparing neuroimaging correlates in TBI subjects with depression versus TBI subjects without depression, controlled for the time interval between TBI occurrence and acquisition of neuroimaging). Results A final cohort of 10 articles resulted, comprising the findings from 423 civilians with brain injury, 129 of which developed post-TBI depression. Four articles studied mild TBI, three mild/moderate, one moderate/severe, and two all-comers, with nine articles focusing on single TBI and one including both single and recurrent injuries. Spatially convergent structural abnormalities in individuals with TBI and co-occurring syndromal depression were identified primarily in bilateral frontal regions, particularly in those with damage to the left frontal lobe and prefrontal cortices, as well as temporal regions including bilateral temporal lobes, the left superior temporal gyrus, and bilateral hippocampi. Various parietal regions and the nucleus accumbens were also implicated. EEG studies showed supporting evidence of functional changes in frontal regions. Conclusion Additional inquiry with attention to TBI without depression control groups, consistent TBI definitions, previous TBI, clinically diagnosed syndromal depression, imaging timing post-injury, acute prospective design, functional neuroimaging, and well-defined neuroanatomical regions of interest is crucial to extrapolating finer discrepancies between primary and TBI-related depression.

Objectives Postictal confusion is encountered among most patients following electro-convulsive therapy (ECT). This study aimed to test the capabilities of a point-of-care electroencephalography (EEG) method to quantitatively measure and monitor postictal confusion immediately following ECT. We evaluated whether a two-channel frontal EEG device may provide a purely quantitative measure of the postictal state that could aid in the continuous, clinical monitoring of patients following ECT. Methods 50 patients receiving ECT at the University of Iowa Hospitals and Clinics were recruited for this study. Subsequently, we obtained 5 min of frontal bispectral EEG (BSEEG) recording from a hand-held EEG device at baseline and 10–20 min following ECT. We performed power spectral density analysis to yield a “BSEEG” score and to capture the difference between patients at baseline and after ECT. Results The BSEEG score was demonstrated to be a significant indicator of postictal confusion compared to baseline. For 5 patients, we also obtained continuous EEG recordings following ECT to determine the time course required for a patient's BSEEG score to return to baseline. In this subset of patients, it took between 2 and 3 h in duration for the BSEEG score to return to the baseline range. Conclusions In this pilot study, we showed that BSEEG score was able to distinguish between baseline condition and postictal confusion in patients treated with ECT, and assess the duration for recovery from postictal confusion following ECT. BSEEG may provide a more sensitive measure of arousal in patients following ECT compared to traditional survey-based methods.

Repetitive transcranial magnetic stimulation (rTMS) has demonstrated antidepressant efficacy but has limited evidence in depression associated with traumatic brain injury (TBI). Here, we investigate the use of rTMS targeted with individualized resting-state network mapping (RSNM) of dorsal attention network (DAN) and default mode network (DMN) in subjects with treatment-resistant depression associated with concussive or moderate TBI. The planned sample size was 50 with first interim analysis planned at 20, but only 15 were enrolled before the study was terminated for logistical reasons. Subjects were randomized to 20 sessions of bilateral rTMS (4000 left-sided excitatory pulses, 1000 right-sided inhibitory pulses) or sham. Treatment was targeted to the dorsolateral prefrontal cluster with maximal difference between DAN and DMN correlations based on resting-state functional magnetic resonance imaging with individualized RSNM. Mean improvement in the primary outcome, Montgomery-Asberg Depression Rating Scale (MADRS), was 56% ± 14% (n = 9) with active treatment and 27% ± 25% (n = 5) with sham (Cohen's d = 1.43). One subject randomized to sham withdrew before starting treatment. There were no seizures or other significant adverse events. MADRS improvement was inversely correlated with functional connectivity between the right-sided stimulation site and the subgenual anterior cingulate cortex (sgACC; r = -0.68, 95% confidence interval 0.03-0.925). Active treatment led to increased sgACC-DMN connectivity (d = 1.55) and increased sgACC anti-correlation with the left- and right-sided stimulation sites (d = -1.26 and -0.69, respectively). This pilot study provides evidence that RSNM-targeted rTMS is feasible in TBI patients with depression. Given the dearth of existing evidence-based treatments for depression in this patient population, these preliminarily encouraging results indicate that larger controlled trials are warranted.

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.