Cognition and Ventral Attention Network Connectivity: Associations With Treatment Response in Posttraumatic Stress Disorder.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is a highly heterogeneous disorder, which makes it difficult to link clinical phenotypes with biomarkers to improve treatment outcomes. Findings from previous studies suggest that cognitive measures such as verbal memory or attention paired with within-ventral attention network (VAN) or salience network resting-state functional connectivity may predict treatment response among individuals with PTSD. METHODS: In a sample comprising 20 individuals with PTSD and 10 healthy control group individuals, the investigators subtyped individuals by using both discriminant function analysis and standardized norms for a single measure of memory and neuropsychological batteries of memory, attention, and executive functioning; attempted to replicate previous findings of lower within-VAN connectivity among individuals with cognitive impairment; and explored whether within-VAN connectivity paired with cognitive impairment predicted treatment outcomes. RESULTS: PTSD patients with cognitive impairment (defined by using a discriminant function analysis with verbal memory performance) had greater within-VAN resting-state functional connectivity compared with control group individuals and cognitively intact PTSD patients at a level that fell short of statistical significance (F=3.41; df=2, 21; ηp2=0.237). The interaction between verbal memory performance and within-VAN connectivity also predicted treatment-related change in PTSD symptoms at a level that also fell short of statistical significance (ß=-0.442). CONCLUSIONS: These findings somewhat support the clinical utility of identifying cognitive phenotypes within PTSD (by using discriminant function analysis and verbal memory performance) to predict treatment outcomes.

Telemedicine-Based Cognitive Examinations During COVID-19 and Beyond: Perspective of the Massachusetts General Hospital Behavioral Neurology & Neuropsychiatry Group.

Telehealth and telemedicine have encountered explosive growth since the beginning of the COVID-19 pandemic, resulting in increased access to care for patients located far from medical centers and clinics. Subspecialty clinicians in behavioral neurology & neuropsychiatry (BNNP) have implemented the use of telemedicine platforms to perform cognitive examinations that were previously office based. In this perspective article, BNNP clinicians at Massachusetts General Hospital (MGH) describe their experience performing cognitive examinations via telemedicine. The article reviews the goals, prerequisites, advantages, and potential limitations of performing a video- or telephone-based telemedicine cognitive examination. The article shares the approaches used by MGH BNNP clinicians to examine cognitive and behavioral areas, such as orientation, attention and executive functions, language, verbal learning and memory, visual learning and memory, visuospatial function, praxis, and abstract abilities, as well as to survey for neuropsychiatric symptoms and assess activities of daily living. Limitations of telemedicine-based cognitive examinations include limited access to and familiarity with telecommunication technologies on the patient side, limitations of the technology itself on the clinician side, and the limited psychometric validation of virtual assessments. Therefore, an in-person examination with a BNNP clinician or a formal in-person neuropsychological examination with a neuropsychologist may be recommended. Overall, this article emphasizes the use of standardized cognitive and behavioral assessment instruments that are either in the public domain or, if copyrighted, are nonproprietary and do not require a fee to be used by the practicing BNNP clinician.

Neurobiological Mechanisms Of Depression Following Traumatic Brain Injury.

OBJECTIVE: Depression is among the most pervasive and debilitating neuropsychiatric sequelae experienced by patients following a traumatic brain injury (TBI). While the individual mechanisms underlying depression and TBI have been widely studied, the neurobiological bases of depression after TBI remain largely unknown. This article highlights the potential mechanisms of action implicated in depression after TBI. RESULTS: We review putative mechanisms of action including neuroinflammation, neuroendocrine dysregulation, metabolic abnormalities, and neurotransmitter and circuitry dysfunction. We also identify the current limitations in the field and propose directions for future research. CONCLUSION: An improved understanding of the underlying mechanisms will aid the development of precision-guided and personalized treatments for patients suffering from depression after TBI.

Associations between residual hyperarousal and insomnia symptoms in veterans following a 2-week intensive outpatient program for posttraumatic stress disorder.

Many returning military service members and veterans who were deployed following the September 11, 2001, terrorist attacks (9/11) suffer from posttraumatic stress disorder (PTSD) and insomnia. Although intensive treatment programs for PTSD have shown promise in the treatment of PTSD symptoms, recent research has demonstrated that sleep disturbance shows little improvement following intensive trauma-focused treatment. The aim of the present study was to evaluate changes in self-reported insomnia symptoms among veterans and service members following participation in a 2-week intensive program for PTSD. We further aimed to investigate if residual PTSD symptoms, specifically hyperarousal, were associated with residual insomnia symptoms. Participants (N = 326) completed self-report assessments of insomnia, PTSD symptoms, and depressive symptoms at pre- and posttreatment. At pretreatment, 73.9% of participants (n = 241) met the criteria for moderate or severe insomnia, whereas at posttreatment 67.7% of participants (n = 203) met the criteria. Results of paired t tests demonstrated statistically significant differences between pre- and posttreatment Insomnia Severity Index scores; however, the effect size was small, d = 0.34. Analyses revealed that posttreatment hyperarousal symptoms were associated with posttreatment insomnia. These findings suggest that although an intensive program for service members and veterans with PTSD may significantly reduce insomnia symptoms, clinically meaningful residual insomnia symptoms remain. Further research is warranted to elucidate the association between residual hyperarousal and insomnia symptoms following intensive trauma-focused treatment.

Levodopa-Induced Dyskinesia Are Mediated by Cortical Gamma Oscillations in Experimental Parkinsonism.

BACKGROUND: Levodopa is the most efficacious drug in the symptomatic therapy of motor symptoms in Parkinson's disease (PD); however, long-term treatment is often complicated by troublesome levodopa-induced dyskinesia (LID). Recent evidence suggests that LID might be related to increased cortical gamma oscillations. OBJECTIVE: The objective of this study was to test the hypothesis that cortical high-gamma network activity relates to LID in the 6-hydroxydopamine model and to identify new biomarkers for adaptive deep brain stimulation (DBS) therapy in PD. METHODS: We recorded and analyzed primary motor cortex (M1) electrocorticogram data and motor behavior in freely moving 6-OHDA lesioned rats before and during a daily treatment with levodopa for 3 weeks. The results were correlated with the abnormal involuntary movement score (AIMS) and used for generalized linear modeling (GLM). RESULTS: Levodopa reverted motor impairment, suppressed beta activity, and, with repeated administration, led to a progressive enhancement of LID. Concurrently, we observed a highly significant stepwise amplitude increase in finely tuned gamma (FTG) activity and gamma centroid frequency. Whereas AIMS and FTG reached their maximum after the 4th injection and remained on a stable plateau thereafter, the centroid frequency of the FTG power continued to increase thereafter. Among the analyzed gamma activity parameters, the fraction of longest gamma bursts showed the strongest correlation with AIMS. Using a GLM, it was possible to accurately predict AIMS from cortical recordings. CONCLUSIONS: FTG activity is tightly linked to LID and should be studied as a biomarker for adaptive DBS. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Baseline Cognitive Performance and Treatment Outcomes From Cognitive-Behavioral Therapies for Posttraumatic Stress Disorder: A Naturalistic Study.

OBJECTIVE: Approximately 5%-20% of U.S. troops returning from Iraq and Afghanistan have posttraumatic stress disorder (PTSD), and another 11%-23% have traumatic brain injury (TBI). Cognitive-behavioral therapies (CBTs) are empirically validated treatment strategies for PTSD. However, cognitive limitations may interfere with an individual's ability to adhere to as well as benefit from such therapies. Comorbid TBI has not been systematically taken into consideration in PTSD outcome research or in treatment planning guidance. The authors hypothesized that poorer pretreatment cognitive abilities would be associated with poorer treatment outcomes from CBTs for PTSD. METHODS: This study was designed as a naturalistic examination of treatment as usual in an outpatient clinic that provides manualized CBTs for PTSD to military service members and veterans. Participants were 23 veterans, aged 18-50 years, with combat-related PTSD and a symptom duration of more than 1 year. Of these, 16 participants had mild TBI (mTBI). Predictor variables were well-normed objective tests of cognitive ability measured at baseline. Outcome variables were individual slopes of change of the PTSD Checklist for DSM-5 (PCL-5) and the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) over weeks of treatment, and of pretreatment-to-posttreatment change in PCL-5 and CAPS-5 (ΔPCL-5 and ΔCAPS-5, respectively). RESULTS: Contrary to prediction, neither pretreatment cognitive performance nor the presence of comorbid mTBI predicted poorer response to CBTs for PTSD. CONCLUSIONS: These results discourage any notion of excluding patients with PTSD and poorer cognitive ability from CBTs.

Telemedicine in Behavioral Neurology-Neuropsychiatry: Opportunities and Challenges Catalyzed by COVID-19.

Coronavirus 2019 (COVID-19) has profoundly impacted the well-being of society and the practice of medicine across health care systems worldwide. As with many other subspecialties, the clinical paradigm in behavioral neurology and neuropsychiatry (BN-NP) was transformed abruptly, transitioning to real-time telemedicine for the assessment and management of the vast majorities of patient populations served by our subspecialty. In this commentary, we outline themes from the BN-NP perspective that reflect the emerging lessons we learned using telemedicine during the COVID-19 pandemic. Positive developments include the ability to extend consultations and management to patients in our high-demand field, maintenance of continuity of care, enhanced ecological validity, greater access to a variety of well-reimbursed telemedicine options (telephone and video) that help bridge the digital divide, and educational and research opportunities. Challenges include the need to adapt the mental state examination to the telemedicine environment, the ability to perform detailed motor neurologic examinations in patients where motor features are important diagnostic considerations, appreciating nonverbal cues, managing acute safety and behavioral concerns in less controlled environments, and navigating intervention-based (neuromodulation) clinics requiring in-person contact. We hope that our reflections help to catalyze discussions that should take place within the Society for Behavioral and Cognitive Neurology, the American Neuropsychiatric Association, and allied organizations regarding how to optimize real-time telemedicine practices for our subspecialty now and into the future.

Cognitive Impairment and Predicting Response to Treatment in an Intensive Clinical Program for Post-9/11 Veterans With Posttraumatic Stress Disorder.

OBJECTIVE: This study examined whether objectively measured pretreatment cognitive impairment predicted worse response to treatment for posttraumatic stress disorder. Participants were 113 veterans and active duty service members who participated in a new multidisciplinary 2-week intensive clinical program that included individual trauma-focused cognitive-behavioral therapy, group psychotherapy, psychoeducation, skills-building groups, and complementary and alternative medicine treatments (mean age: 39.7 years [SD=8.5]; 20% women). METHODS: Prior to treatment, participants completed a brief computerized cognitive battery (CNS Vital Signs) and were operationalized as having cognitive impairment if they scored in the ≤5th percentile on two or more of five core cognitive domains. Participants completed measures of traumatic stress, depression, cognitive self-efficacy, and satisfaction with their ability to participate in social roles before and after treatment. RESULTS: There were no significant correlations between pretreatment individual cognitive test scores and change in the clinical outcome measures. One-half of the study sample (49.6%) met criteria for cognitive impairment. In a mixed multivariate analysis of variance, the interaction between cognitive impairment and time was not significant (F=0.83, df=4, 108, p=0.51), indicating that the pre- to posttreatment changes in outcome scores were not significantly different for the cognitively impaired group compared with the cognitively intact group. The multivariate main effect for time was significant (F=36.75, df=4, 108, p<0.001). Follow-up univariate tests revealed significant improvement in traumatic stress, depression, cognitive self-efficacy, and satisfaction with social roles after treatment. CONCLUSIONS: Cognitive impairment was not associated with worse response to treatment in veterans with severe and complex mental health problems. Veterans with and without cognitive impairment reported large improvements in symptoms and functioning after treatment.

Cortical thickness alterations linked to somatoform and psychological dissociation in functional neurological disorders.

BACKGROUND: Links between dissociation and functional neurological disorder (FND)/conversion disorder are well-established, yet the pathophysiology of dissociation remains poorly understood. This MRI study investigated structural alterations associated with somatoform and psychological dissociation in FND. We hypothesized that multimodal, paralimbic cingulo-insular regions would relate to the severity of somatoform dissociation in patients with FND. METHODS: FreeSurfer cortical thickness and subcortical volumetric analyses were performed in 26 patients with motor FND and 27 matched healthy controls. Patients with high dissociation as measured by the Somatoform Dissociation Questionnaire-20 (SDQ) or Dissociative Experiences Scale (DES) were compared to controls in stratified analyses. Within-group analyses were also performed with SDQ and DES scores in patients with FND. All cortical thickness analyses were whole-brain corrected at the cluster-wise level. RESULTS: Patients with FND and high somatoform dissociation (SDQ > 35) showed reduced left caudal anterior cingulate cortex (ACC) cortical thickness compared to controls. In within-group analyses, SDQ scores inversely correlated with left caudal ACC cortical thickness in patients with FND. Depersonalization/derealization scores positively correlated with right lateral occipital cortical thickness. Both within-group findings remained statistically significant controlling for trait anxiety/depression, borderline personality disorder and post-traumatic stress disorder, adverse life events, and motor FND subtypes in post-hoc analyses. CONCLUSION: Using complementary between-group and within-group analyses, an inverse association between somatoform dissociation and left caudal ACC cortical thickness was observed in patients with FND. A positive relationship was also appreciated between depersonalization/derealization severity and cortical thickness in visual association areas. These findings advance our neuropathobiological understanding of dissociation in FND. Hum Brain Mapp 39:428-439, 2018. © 2017 Wiley Periodicals, Inc.

Sleep Patterns and Neuropsychiatric Symptoms in Hospitalized Patients With Dementia.

The authors examined 28 dementia inpatients receiving treatment as usual. Beginning-to-end differences in neuropsychiatric symptoms and actigraphic sleep patterns were measured. Using a mixed-model, the authors regressed neuropsychiatric symptoms on average sleep minutes (between-subjects effect) and each night's deviation from average (within-subject effect). Sleep did not significantly differ from beginning to end of participation, whereas neuropsychiatric symptoms did. Average sleep minutes predicted average neuropsychiatric symptoms (p=0.002), but each night's deviation from the average did not predict next day's symptoms (p=0.90). These findings raise questions about the immediate benefits of treating sleep-wake disturbances on neuropsychiatric symptoms in hospitalized inpatients with dementias.

Positive Association Between Nightmares and Heart Rate Response to Loud Tones: Relationship to Parasympathetic Dysfunction in PTSD Nightmares.

Seventy-three women with posttraumatic stress disorder (PTSD) resulting from rape or physical assault participated in a loud-tone procedure, while skin conductance (SC), heart rate, and electromyogram responses were recorded. Pearson correlations were examined between each psychophysiological response and Clinician-Administered PTSD Scale (CAPS) symptom scores. Significant correlations were adjusted for each remaining individual PTSD symptom score. Heart rate response (HRR) significantly correlated with CAPS total score and with CAPS nightmares. The relationship between HRR and nightmares remained significant after controlling for each of the other 16 individual PTSD symptoms, for the remaining reexperiencing cluster, and for CAPS total score. The zero-order correlations between SC response and nightmares and between electromyography response and nightmares were both not significant. The association of nightmares with larger HRR in the absence of an association with larger SC response likely reflects reduced parasympathetic tone. Thus, our findings indirectly support a role for reduced parasympathetic tone in PTSD nightmares.

Mixed-Handedness in Identical Twins Discordant for Combat Exposure in Vietnam: Relationship to Posttraumatic Stress Disorder.

This study evaluated the degree of mixed-handedness in predominantly right-handed Vietnam combat veteran twins and their identical, combat-unexposed cotwins. The "high-risk" cotwins of combat veterans with combat-related posttraumatic stress disorder (PTSD) had more mixed-handedness (i.e., less right-handedness) than the "low-risk" cotwins of combat veterans without PTSD. Self-reported combat exposure in combat-exposed twins was a mediator of the association between handedness in their unexposed cotwins and PTSD in the twins themselves. We conclude that mixed-handedness is a familial risk factor for combat-related PTSD. This risk may be mediated in part by a proclivity for mixed-handed soldiers and Marines to experience heavier combat.

Evaluation and treatment of migraine in the emergency department: a review.

Head pain is the fifth most common reason for emergency department (ED) visits. It is second only to focal weakness as the most common reason for neurological consultation in the ED. This manuscript reviews how patients with migraine, the most common primary headache disorder for which patients seek medical treatment, are managed in the ED. We discuss existing guidelines for head imaging in patients with migraine, recommended pharmacologic treatments, and current treatment trends. We also review studies evaluating the discharge care of migraine patients in the ED. With the goal of standardizing, streamlining, and optimizing ED-based migraine care, we offer ideas for future research to improve the evaluation, treatment, and discharge care of patients who present to an ED with acute migraine.

PTSD and TBI co-morbidity: scope, clinical presentation and treatment options.

PRIMARY OBJECTIVE: To summarize the literature on post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) and their co-morbidity, focusing on diagnosis, clinical symptoms and treatment issues relevant to the clinician. RESEARCH DESIGN: Review of the literature. METHODS AND PROCEDURES: Pubmed searches were performed using the terms post-traumatic stress disorder, traumatic brain injury, sleep, cognitive, depression, anxiety, treatment and combinations of these terms. Those articles relevant to the objective were included. MAIN OUTCOMES AND RESULTS: This study presents pathophysiological, neuroimaging and clinical data on co-morbid PTSD and TBI. It reviews associated conditions, emphasizing the impact of cognitive and sleep problems. It summarizes the emerging literature on treatment effectiveness for co-morbid PTSD and TBI, including psychotherapy, pharmacotherapy and cognitive rehabilitation. CONCLUSIONS: Both PTSD and TBI commonly occur in the general population, both share some pathophysiological characteristics and both are associated with cognitive impairment and sleep disruption. PTSD and TBI present with a number of overlapping symptoms, which can lead to over-diagnosis or misdiagnosis. Both conditions are associated with co-morbidities important in diagnosis and treatment planning. More research is needed to elucidate what treatments are effective in PTSD and TBI co-morbidity and on factors predictive of treatment success.

Stress, PTSD, and dementia.

The physiological consequences of acute and chronic stress on a range of organ systems have been well documented after the pioneering work of Hans Selye more than 70 years ago. More recently, an association between exposure to stressful life events and the development of later-life cognitive dysfunction has been proposed. Several plausible neurohormonal pathways and genetic mechanisms exist to support such an association. However, many logistical and methodological barriers must be overcome before a defined causal linkage can be firmly established. Here the authors review recent studies of the long-term cognitive consequences of exposures to cumulative ordinary life stressors as well as extraordinary traumatic events leading to posttraumatic stress disorder. Suggestive effects have been demonstrated for the role of life stress in general, and posttraumatic stress disorder in particular, on a range of negative cognitive outcomes, including worse than normal changes with aging, Alzheimer's disease, and vascular dementia. However, given the magnitude of the issue, well-controlled studies are relatively few in number, and the effects they have revealed are modest in size. Moreover, the effects have typically only been demonstrated on a selective subset of measures and outcomes. Potentially confounding factors abound and complicate causal relationships despite efforts to contain them. More well-controlled, carefully executed longitudinal studies are needed to confirm the apparent association between stress and dementia, clarify causal relationships, develop reliable antemortem markers, and delineate distinct patterns of risk in subsets of individuals.

Pharmacologic Management of the Sequelae of Traumatic Brain Injuries.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.Prim Care Companion CNS Disord 2024;26(4):23f03670. Author affiliations are listed at the end of this article.

Longitudinal changes in the PTSD symptom network following trauma-focused treatment in military populations: Identifying central symptoms and the role of military sexual trauma.

Posttraumatic stress disorder (PTSD) is a debilitating condition affecting military populations, with a higher prevalence compared to the general population. Despite the development of first-line trauma-focused treatments such as Cognitive Processing Therapy (CPT) and Prolonged Exposure Therapy (PE), a significant proportion of patients continue to experience persistent PTSD symptoms following treatment. This study utilized network analysis to explore the PTSD symptom network's dynamics pre- and post- trauma-focused treatment and investigated the role of military sexual trauma (MST) history in shaping the network. Network analysis is a novel approach that can guide treatment target areas. The sample was comprised of 1648 service members and veterans who participated in a two-week intensive PTSD treatment program, which included completion of evidenced-based individual therapy as well as skill-building focused group therapy. PTSD severity was assessed using the PTSD Checklist for DSM-5 at baseline and post-treatment. Network analyses revealed strong connections within symptom clusters, with negative emotions emerging as one of the most central symptoms. Interestingly, the symptom network's overall structure remained stable following treatment, whereas global strength significantly increased. MST history did not significantly impact the network's structure or its change relative to treatment. Future research should further examine whether targeting negative emotions optimizes PTSD treatment outcomes for military populations.

Traumatic Brain Injuries: Manifestations, Evaluation, Management, and Outcomes.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.Prim Care Companion CNS Disord 2024;26(3):23f03667. Author affiliations are listed at the end of this article.

Innovative outpatient treatment for veterans and service members and their family members.

In 2009, Massachusetts General Hospital and the Red Sox Foundation launched Home Base, a nonprofit dedicated to providing care to veterans, service members, and their loved ones who struggle with the invisible wounds of war free of charge. Significant needs exist for mental health services in each of these populations, and a need for innovative approaches to address shortcomings in existing treatment models. Three inventive components of our programming are highlighted herein: a Veteran Outreach Team, which helps to engage patients in care, programming, and services specifically for family members, and an intensive outpatient substance use treatment program. More than 4,000 patients, 3,031 veterans and service members, and 1,025 family members have engaged in treatment at Home Base. Patients were asked to complete post-treatment self-measures, including a satisfaction questionnaire via an electronic data collection system. The vast majority of individuals who engaged in our treatment model were satisfied with the care they received (>92%) and would refer their peers to the Home Base program (>75%). Data from 78 individuals who completed the dual diagnosis services demonstrated large effect sizes in reductions in alcohol use and comorbid mental health symptoms. These data suggest that novel components to the standard outpatient mental health model might provide substantive benefits for the patients served. While internal data is prone to a lack of generalizability, these additional offerings help ameliorate patients' expressed shortcomings with existing models; present literature that describes the benefits that these additions provide is also reviewed. The lessons learned and limitations are discussed.

Comparison of autonomic reactivity to trauma and nightmare imagery: A Pilot Study.

Study Objectives: Trauma-related nightmares (TRNs) are a hallmark symptom of PTSD and are highly correlated with PTSD severity and poor sleep quality. Given the salience and arousal associated with TRNs, they might be an effective target for imaginal exposures during Prolonged Exposure (PE) therapy. As a first step in this line of research, the current study compared participants' emotional reactivity during recollection of TRNs to their recollection of the index traumatic event. Methods: Seventeen trauma-exposed participants with clinical or sub-clinical PTSD who reported frequent TRNs engaged in script-driven imagery using scripts depicting their index trauma and their most trauma-like TRN. Heart rate (HRR), skin conductance (SCR), corrugator EMG (EMGR) responses, and emotional ratings were recorded. Results: HRR, SCR, and EMGR did not differ significantly between trauma-related and TRN scripts. Bayesian analyses confirmed support for the null hypothesis, indicating no differences. With the exception of "Sadness," for which TRNs elicited significantly lower ratings than trauma scripts, individual emotion ratings showed no significant differences, suggesting likely parity between the emotionality of trauma-related and TRN recollections. Conclusions: Together, TRN content elicited psychophysiological reactivity similar to that of the index trauma in this pilot study. Upon replication, studies testing TRNs as potential targets for imaginal exposures during PE may be warranted.