A conceptual framework for a neurophysiological basis of art therapy for PTSD.

Post-traumatic stress disorder (PTSD) is a heterogeneous condition that affects many civilians and military service members. Lack of engagement, high dropout rate, and variable response to psychotherapy necessitates more compelling and accessible treatment options that are based on sound neuroscientific evidence-informed decision-making. Art therapy incorporates elements proven to be effective in psychotherapy, such as exposure, making it a potentially valuable treatment option. This conceptual paper aims to inform the neurophysiological rationale for the use of art therapy as a therapeutic approach for individuals with PTSD. A narrative synthesis was conducted using literature review of empirical research on the neurophysiological effects of art therapy, with supporting literature on neuroaesthetics and psychotherapies to identify art therapy factors most pertinent for PTSD. Findings were synthesized through a proposed framework based on the triple network model considering the network-based dysfunctions due to PTSD. Art therapy's active components, such as concretization and metaphor, active art engagement, emotion processing and regulation, perspective taking and reframing, and therapeutic alliance, may improve symptoms of PTSD and prompt adaptive brain functioning. Given the scarcity of rigorous studies on art therapy's effectiveness and mechanisms of alleviating PTSD symptoms, the suggested framework offers a neurophysiological rationale and a future research agenda to investigate the impact of art therapy as a therapeutic approach for individuals with PTSD.

Temporal Profile of Serum Neurofilament Light (NF-L) and Heavy (pNF-H) Level Associations With 6-Month Cognitive Performance in Patients With Moderate-Severe Traumatic Brain Injury.

OBJECTIVE: Identification of biomarkers of cognitive recovery after traumatic brain injury (TBI) will inform care and improve outcomes. This study assessed the utility of neurofilament (NF-L and pNF-H), a marker of neuronal injury, informing cognitive performance following moderate-to-severe TBI (msTBI). SETTING: Level 1 trauma center and outpatient via postdischarge follow-up. PARTICIPANTS: N = 94. Inclusion criteria: Glasgow Coma Scale score less than 13 or 13-15 with clinical evidence of moderate-to-severe injury traumatic brain injury on clinical imaging. Exclusion criteria: neurodegenerative condition, brain death within 3 days after injury. DESIGN: Prospective observational study. Blood samples were collected at several time points post-injury. Cognitive testing was completed at 6 months post-injury. MAIN MEASURES: Serum NF-L (Human Neurology 4-Plex B) pNF-H (SR-X) as measured by SIMOA Quanterix assay. Divided into 3 categorical time points at days post-injury (DPI): 0-15 DPI, 16-90 DPI, and >90 DPI. Cognitive composite comprised executive functioning measures derived from 3 standardized neuropsychological tests (eg, Delis-Kaplan Executive Function System: Verbal Fluency, California Verbal Learning Test, Second Edition, Wechsler Adult Intelligence Scale, Third Edition). RESULTS: pNF-H at 16-90 DPI was associated with cognitive outcomes including a cognitive-executive composite score at 6 months (ß = -.430, t34 = -3.190, P = .003). CONCLUSIONS: Results suggest that "subacute" elevation of serum pNF-H levels may be associated with protracted/poor cognitive recovery from msTBI and may be a target for intervention. Interpretation is limited by small sample size and including only those who were able to complete cognitive testing.

Parallel Cerebrospinal Fluid and Serum Temporal Profile Assessment of Axonal Injury Biomarkers Neurofilament-Light Chain and Phosphorylated Neurofilament-Heavy Chain: Associations With Patient Outcome in Moderate-Severe Traumatic Brain Injury.

Neurofilament-light chain (NF-L) and phosphorylated neurofilament-heavy chain (pNF-H) are axonal proteins that have been reported as potential diagnostic and prognostic biomarkers in traumatic brain injury (TBI). However, detailed temporal profiles for these proteins in blood, and interrelationships in the acute and chronic time periods post-TBI have not been established. Our objectives were: 1) to characterize acute-to-chronic serum NF-L and pNF-H profiles after moderate-severe TBI, as well as acute cerebrospinal fluid (CSF) levels; 2) to evaluate CSF and serum NF-L and pNF-H associations with each other; and 3) to assess biomarker associations with global patient outcome using both the Glasgow Outcome Scale-Extended (GOS-E) and Disability Rating Scale (DRS). In this multi-cohort study, we measured serum and CSF NF-L and pNF-H levels in samples collected from two clinical cohorts (University of Pittsburgh [UPITT] and Baylor College of Medicine [BCM]) of individuals with moderate-severe TBI. The UPITT cohort includes 279 subjects from an observational cohort study; we obtained serum (n = 277 unique subjects) and CSF (n = 95 unique subjects) daily for 1 week, and serum every 2 weeks for 6 months. The BCM cohort included 103 subjects from a previous randomized clinical trial of erythropoietin and blood transfusion threshold after severe TBI, which showed no effect on neurological outcome between treatment arms; serum (n = 99 unique subjects) and CSF (n = 54 unique subjects) NF-L and pNF-H levels were measured at least daily during Days (D) 0-10 post-injury. GOS-E and DRS were assessed at 6 months (both cohorts) and 12 months (UPITT cohort only). Results show serum NF-L and pNF-H gradually rise during the first 10 days and peak at D20-30 post-injury. In the UPITT cohort, acute (D0-6) NF-L and pNF-H levels correlate within CSF and serum (Spearman r = 0.44-0.48; p < 0.05). In the UPITT cohort, acute NF-L CSF and serum levels, as well as chronic (Months [M]2-6) serum NF-L levels, were higher among individuals with unfavorable GOS-E and worse DRS at 12 months (p < 0.05, all comparisons). In the BCM cohort, higher acute serum NF-L levels were also associated with unfavorable GOS-E. Higher pNF-H serum concentrations (D0-6 and M2-6), but not CSF pNF-H, were associated with unfavorable GOS-E and worse DRS (p < 0.05, all comparisons) in the UPITT cohort. Relationships between biomarker levels and favorable outcome persisted after controlling for age, sex, and Glasgow Coma Scale. This study shows for the first time that serum levels of NF-L and pNF-H peak at D20-30 post-TBI. Serum NF-L levels, and to a lesser extent pNF-H levels, are robustly associated with global patient outcomes and disability after moderate-severe TBI. Further studies on clinical utility as prognosis and treatment-response indicators are needed.

Preliminary evidence of transcutaneous vagus nerve stimulation effects on sleep in veterans with post-traumatic stress disorder.

Sleep problems are common among veterans with post-traumatic stress disorder and closely associated with hyperarousal symptoms. Transcutaneous vagus nerve stimulation (tVNS) may have potential to improve sleep quality in veterans with PTSD through effects on brain systems relevant to hyperarousal and sleep-wake regulation. The current pilot study examines the effect of 1 h of tVNS administered at "lights out" on sleep architecture, microstructure, and autonomic activity. Thirteen veterans with PTSD completed two nights of laboratory-based polysomnography during which they received 1 h of either active tVNS (tragus) or sham stimulation (earlobe) at "lights out" with randomised order. Sleep staging and stability metrics were derived from polysomnography data. Autonomic activity during sleep was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (RSAP-B ). Paired t-tests revealed a small decrease in the total sleep time (d = -0.31), increase in N3 sleep (d = 0.23), and a small-to-moderate decrease in REM sleep (d = -0.48) on nights of active tVNS relative to sham stimulation. tVNS was also associated with a moderate reduction in cyclic alternating pattern (CAP) rate (d = -0.65) and small-to-moderate increase in RSAP-B during NREM sleep. Greater NREM RSAP-B was associated with a reduced CAP rate and NREM alpha power. This pilot study provides preliminary evidence that tVNS may improve sleep depth and stability in veterans with PTSD, as well as increase parasympathetically mediated nocturnal autonomic activity. These results warrant continued investigation into tVNS as a potential tool for treating sleep disturbance in veterans with PTSD.

Presurgical microstructural coherence predicts cognitive change for bariatric surgery patients.

OBJECTIVE: This observational study examined the relationship between presurgical white matter microstructural coherence and cognitive change after weight loss. It was hypothesized that higher baseline fractional anisotropy (FA) would predict greater baseline and change cognition. METHODS: A sample of 24 adults (BMI ≥ 35 kg/m2 ) underwent neuropsychological assessment at baseline and 12 weeks after bariatric surgery. A magnetic resonance imaging brain scan was administered at baseline and processed through Tract-Based Spatial Statistics to compute FA in white matter tracts of interest. Composite scores for attention, learning, processing speed, executive function, verbal fluency, working memory, and overall cognition were calculated. RESULTS: As expected, FA in some tracts of interest was significantly (p < 0.05) positively associated with change in cognition. Inverse relationships were observed between baseline FA and presurgical cognition, which may be explained by increased medial and radial diffusivity and preserved axonal diffusivity. Cognition generally improved after surgery; however, relative but clinically nonsignificant deterioration was observed on learning measures. Poorer baseline cognitive performance was associated with greater postsurgical cognitive improvement. CONCLUSIONS: Presurgical microstructural coherence is associated with magnitude of cognitive change after weight loss. An observed reduction in learning suggests that bariatric surgery may lead to negative outcomes in some cognitive domains, at least temporarily.

Effects of sleep disturbance on trauma-focused psychotherapy outcomes in posttraumatic stress disorder: A systematic review.

This study aimed to synthesize existing research on the effects of sleep disturbances on trauma-focused psychotherapy outcomes in adults with posttraumatic stress disorder (PTSD). A systematic review using PubMed, PsycINFO, Embase, Web of Science, and PTSDpubs was performed up to April 2021. Two independent reviewers screened articles for inclusion, performed data extraction, and assessed risk of bias and certainty of the evidence. Narrative synthesis was conducted based on the type of sleep disorder symptom assessed. Sixteen primary studies were included in this review, the majority of which had a high overall risk of bias. Results suggested that sleep disorder symptoms were associated with higher overall PTSD severity across treatment; however, they did not interfere with treatment effectiveness, with the exception of sleep-disordered breathing. Improvements in insomnia, sleep duration, and sleep quality during treatment were associated with greater treatment gains. Certainty of the evidence ranged from low to very low. These results suggest that it may not be necessary to address sleep disorder symptoms prior to initiating trauma-focused psychotherapy. Instead, concurrent treatment of sleep- and trauma-related symptoms may be most beneficial. Continued research is needed to clarify the mechanistic relationship between sleep and treatment outcomes and to guide clinical decision-making.

Change in medial frontal cerebral metabolite concentrations following bariatric surgery.

Obesity is associated with adverse effects on brain health, including an increased risk of neurodegenerative diseases. Changes in cerebral metabolism may underlie or precede structural and functional brain changes. While bariatric surgery is known to be effective in inducing weight loss and improving obesity-related medical comorbidities, few studies have examined whether it may be able to improve brain metabolism. In the present study, we examined changes in cerebral metabolite concentrations in participants with obesity who underwent bariatric surgery. Thirty-five patients with obesity (body mass index ≥ 35 kg/m2 ) were recruited from a bariatric surgery candidate nutrition class. They completed single voxel proton magnetic resonance spectroscopy at baseline (presurgery) and within 1 year postsurgery. Spectra were obtained from a large medial frontal brain region using a PRESS sequence on a 3-T Siemens Verio scanner. The acquisition parameters were TR = 3000 ms and TE = 37 ms. Tissue-corrected metabolite concentrations were determined using Osprey. Paired t-tests were used to examine within-subject change in metabolite concentrations, and correlations were used to relate these changes to other health-related outcomes, including weight loss and glycated hemoglobin (HbA1c ), a measure of blood sugar levels. Bariatric surgery was associated with a reduction in cerebral choline-containing compounds (Cho; t [34] = - 3.79, p < 0.001, d = -0.64) and myo-inositol (mI; t [34] = - 2.81, p < 0.01, d = -0.47) concentrations. There were no significant changes in N-acetyl-aspartate, creatine, or glutamate and glutamine concentrations. Reductions in Cho were associated with greater weight loss (r = 0.40, p < 0.05), and reductions in mI were associated with greater reductions in HbA1c (r = 0.44, p < 0.05). In conclusion, participants who underwent bariatric surgery exhibited reductions in cerebral Cho and mI concentrations, which were associated with improvements in weight loss and glycemic control. Given that elevated levels of Cho and mI have been implicated in neuroinflammation, reduction in these metabolites after bariatric surgery may reflect amelioration of obesity-related neuroinflammatory processes. As such, our results provide evidence that bariatric surgery may improve brain health and metabolism in individuals with obesity.

Resting-state network functional connectivity before and after bariatric surgery.

BACKGROUND: Bariatric surgery is an increasingly popular treatment for patients with severe obesity and related health issues (e.g., diabetes, cardiovascular disease). Studies have identified alterations in functional connectivity both in obesity and following surgical treatment for severe obesity. OBJECTIVE: This study aimed to assess brain function via resting-state within-network connectivity in bariatric surgery patients with severe obesity. SETTING: University hospital. METHODS: Thirty-four bariatric surgery patients completed functional neuroimaging at baseline and postoperatively (goal, 12 weeks; actual, 16 weeks, on average). They also self-reported health information. Baseline resting-state functional connectivity (RSFC) was predicted by baseline age, body mass index (BMI), continuous positive airway pressure use, and reported history of rheumatoid arthritis and type 2 diabetes. Change in RSFC was assessed using the same predictors. This model was run with and without controlling for baseline RSFC. RESULTS: Higher baseline BMI predicted lower baseline RSFC in 3 networks. Lower baseline RSFC also was related to rheumatoid arthritis and type 2 diabetes. Difference between baseline and follow-up RSFC was strongly negatively associated with baseline RSFC. Controlling for baseline RSFC, type 2 diabetes negatively predicted RSFC difference. CONCLUSIONS: RSFC may reflect brain dysfunction in patients with obesity and related diseases. That less connectivity at baseline predicted greater positive change suggests that RSFC may be a biomarker of neurocognitive improvement following bariatric surgery. Diseases more prevalent in patients with obesity (e.g., rheumatoid arthritis and type 2 diabetes) along with elevated BMI negatively affect RSFC likely through inflammatory pathways.

The Effects of Transcutaneous Vagus Nerve Stimulation on Functional Connectivity Within Semantic and Hippocampal Networks in Mild Cognitive Impairment.

Better treatments are needed to improve cognition and brain health in people with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Transcutaneous vagus nerve stimulation (tVNS) may impact brain networks relevant to AD through multiple mechanisms including, but not limited to, projection to the locus coeruleus, the brain's primary source of norepinephrine, and reduction in inflammation. Neuropathological data suggest that the locus coeruleus may be an early site of tau pathology in AD. Thus, tVNS may modify the activity of networks that are impaired and progressively deteriorate in patients with MCI and AD. Fifty patients with MCI (28 women) confirmed via diagnostic consensus conference prior to MRI (sources of info: Montreal Cognitive Assessment Test (MOCA), Clinical Dementia Rating scale (CDR), Functional Activities Questionnaire (FAQ), Hopkins Verbal Learning Test - Revised (HVLT-R) and medical record review) underwent resting state functional magnetic resonance imaging (fMRI) on a Siemens 3 T scanner during tVNS (left tragus, n = 25) or sham control conditions (left ear lobe, n = 25). During unilateral left tVNS, compared with ear lobe stimulation, patients with MCI showed alterations in functional connectivity between regions of the brain that are important in semantic and salience functions including regions of the temporal and parietal lobes. Furthermore, connectivity from hippocampi to several cortical and subcortical clusters of ROIs also demonstrated change with tVNS compared with ear lobe stimulation. In conclusion, tVNS modified the activity of brain networks in which disruption correlates with deterioration in AD. These findings suggest afferent target engagement of tVNS, which carries implications for the development of noninvasive therapeutic intervention in the MCI population.

Regional associations of white matter integrity and neurological, post-traumatic stress disorder and autonomic symptoms in Veterans with and without history of loss of consciousness in mild TBI.

Background: Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) share overlapping symptom presentations and are highly comorbid conditions among Veteran populations. Despite elevated presentations of PTSD after mTBI, mechanisms linking the two are unclear, although both have been associated with alterations in white matter and disruptions in autonomic regulation. The present study aimed to determine if there is regional variability in white matter correlates of symptom severity and autonomic functioning in a mixed sample of Veterans with and without PTSD and/or mTBI (N = 77). Methods: Diffusion-weighted images were processed to extract fractional anisotropy (FA) values for major white matter structures. The PTSD Checklist-Military version (PCL-M) and Neurobehavioral Symptom Inventory (NSI) were used to determine symptom domains within PTSD and mTBI. Autonomic function was assessed using continuous blood pressure and respiratory sinus arrythmia during a static, standing angle positional test. Mixed-effect models were used to assess the regional specificity of associations between symptom severity and white matter, with FA, global symptom severity (score), and white matter tract (tract) as predictors. Additional interaction terms of symptom domain (i.e., NSI and PCL-M subscales) and loss of consciousness (LoC) were added to evaluate potential moderating effects. A parallel analysis was conducted to explore concordance with autonomic functioning. Results: Results from the two-way Score × Tract interaction suggested that global symptom severity was associated with FA in the cingulum angular bundle (positive) and uncinate fasciculus (negative) only, without variability by symptom domain. We also found regional specificity in the relationship between FA and autonomic function, such that FA was positively associated with autonomic function in all tracts except the cingulum angular bundle. History of LoC moderated the association for both global symptom severity and autonomic function. Conclusions: Our findings are consistent with previous literature suggesting that there is significant overlap in the symptom presentation in TBI and PTSD, and white matter variability associated with LoC in mTBI may be associated with increased PTSD-spectra symptoms. Further research on treatment response in patients with both mTBI history and PTSD incorporating imaging and autonomic assessment may be valuable in understanding the role of brain injury in treatment outcomes and inform treatment design.

Psychometric properties of the Autonomic Symptoms Checklist in the Lewy body disease module of the uniform dataset.

INTRODUCTION: Autonomic dysfunction is an important feature of Lewy Body Dementia (DLB), but measurement of autonomic symptoms has been limited in both previous research and clinical practice. Accurate measurement of autonomic dysfunction has the potential to improve our understanding of the course and progression of DLB, given that autonomic symptoms typically precede cognitive impairment and are associated with functional impairment. The primary aim of this study was to examine the psychometric properties of the two versions (3.0 and 3.1) of the NACC LBD-module Autonomic Symptom Checklist (ASC). METHODS: Psychometric analyses of the ASC (internal consistency, reliability, factor structure, and validity) were conducted on data acquired from 245 individuals with DLB from the NACC database. ASC V3.0 was contrasted on these attributes to V3.1. RESULTS: Results suggested an underlying factor structure for the ASC, and confirmatory factor analysis (CFA) revealed 3 factors, which generally aligned with discrete autonomic systems. The ASC V3.0 and CFA-identified scales were comparable in terms of reliability, which were both improved relative to the ASC V3.1. In terms of ecological validity, CFA-identified items related to gastrointestinal/thermoregulation symptoms were significantly more associated with functional outcomes compared to the unitary ASC. CONCLUSION: Findings underscore the importance of differentiation within the autonomic system. Future research into autonomic symptom classes and lab-based pathophysiological measurement of autonomic dysfunction in DLB has the potential to support early identification and inform treatment planning.

Functional connectivity of brain networks during semantic processing in older adults.

The neural systems underlying semantic processing have been characterized with functional neuroimaging in young adults. Whether the integrity of these systems degrade with advanced age remains unresolved. The current study examined functional connectivity during abstract and concrete word processing. Thirty-eight adults, aged 55-91, engaged in semantic association decision tasks during a mixed event-related block functional magnetic resonance imaging (fMRI) paradigm. During the semantic trials, the task required participants to make a judgment as to whether pairs were semantically associated. During the rhyme trials, the task required participants to determine if non-word pairs rhymed. Seeds were placed in putative semantic hubs of the left anterior middle temporal gyrus (aMTG) and the angular gyrus (AG), and also in the left inferior frontal gyrus (IFG), an area considered important for semantic control. Greater connectivity between aMTG, AG, and IFG and multiple cortical areas occurred during semantic processing. Connectivity from the three seeds differed during semantic processing: the left AG and aMTG were strongly connected with frontal, parietal, and occipital areas bilaterally, whereas the IFG was most strongly connected with other frontal cortical areas and the AG in the ipsilateral left hemisphere. Notably, the strength and extent of connectivity differed for abstract and concrete semantic processing; connectivity from the left aMTG and AG to bilateral cortical areas was greater during abstract processing, whereas IFG connectivity with left cortical areas was greater during concrete processing. With advanced age, greater connectivity occurred only between the left AG and supramarginal gyrus during the processing of concrete word-pairs, but not abstract word-pairs. Among older adults, robust functional connectivity of the aMTG, AG, and IFG to widely distributed bilateral cortical areas occurs during abstract and concrete semantic processing in a manner consistent with reports from past studies of young adults. There was not a significant degradation of functional connectivity during semantic processing between the ages of 55 and 85 years. As the study focused on semantic functioning in older adults, a comparison group of young adults was not included, limiting generalizability. Future longitudinal neuroimaging studies that compare functional connectivity of young and older adults under different semantic demands will be valuable.

Vertical pseudoneglect: Sensory-attentional versus action-intentional.

INTRODUCTION: Healthy persons demonstrate an upward bias on the vertical-line bisection test (vertical or "altitudinal" pseudoneglect). This bias might be sensory-attentional or action-intentional in origin. To test the action-intention hypothesis, we analyze whether the direction of action has an effect on altitudinal pseudoneglect. METHODS: Twenty-four healthy right-handed adults performed vertical-line bisection on an apparatus designed to distinguish the effects of sensory-attention and action-intention. Depending on hand placement, participants estimated line midpoints with a marker that moved in the same (congruent) or opposite (incongruent) direction as their hand movements. Two binary factors - hand movement in the upward versus downward direction and congruent vs incongruent hand movements - produced four conditions. RESULTS: There was upward deviation from the midline across all conditions. Bisections in the incongruent condition were higher than in the congruent condition. Bisections were also higher with upward hand movements than with downward hand movements. There was not a significant interaction between these factors. CONCLUSIONS: These results suggest that vertical pseudoneglect is primarily influenced by the allocation of allocentric attention, rather than action-intention. However, action-perceptual spatial incongruence increased this deviation. Perhaps the incongruent condition requires greater allocation of attention, but further exploration is needed. Additionally, these results suggest that visual attention follows the direction of motor action. Future studies of visual attention should consider the potential influence of this factor.

Music, Mind, Mood, and Mingling in Alzheimer's Disease and Related Dementias: A Scoping Review.

BACKGROUND: Music-based interventions may help to alleviate neuropsychiatric symptoms of dementia and promote prosocial interactions between individuals living with dementia and their caregivers. However, current literature does not combine these evidence bases toward explanation of how music-based interventions may alleviate symptoms and promote prosocial interactions. OBJECTIVE: We conducted a scoping review to address the following question: what do the evidence bases suggest toward how music therapy or music-based therapeutic interventions might promote prosocial interactions between individuals living with dementia and their caregivers? METHODS: In this review we focused on: 1) quantitative and qualitative evidence of music-based therapies promoting prosocial behaviors in individuals living with dementia, and 2) potential neurobehavioral mechanisms associated with the processes involved with how music may promote prosocial interactions. Databases included PubMed, EBSCOhost's CINAHL and PsycINFO, Cochrane Library (sub-search conducted using ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group), Web of Science, clinicaltrials.gov, ProQuest's Biological Science Collection, the Journal of Music Therapy, Nordic Journal of Music Therapy, and Google Scholar. RESULTS: Sixteen original research studies were included for evidence synthesis. This scoping review reveals the need to define and clarify mechanisms of prosocial interactions between individuals living with dementia and their caregivers considering biological and social factors. These mechanisms may include dynamic interactions between preserved brain regions associated with music-evoked autobiographical memory recall and shifts from negative to positive mood states. CONCLUSION: Defining and clarifying how and to what extent music may promote prosocial behaviors using well-designed and well-controlled mixed-methods studies may positively influence the design of interventions to promote prosocial interactions with caregivers.

Hemodialyzed Individuals' Left Spatial Attentional Bias Is Normalized Following Successful Kidney Transplantation.

BACKGROUND: Healthy people have a leftward spatial attentional bias, called pseudoneglect. Individuals with end-stage renal disease (ESRD) who are receiving hemodialysis often demonstrate an increase in their leftward spatial attentional bias. Whereas a successful kidney transplant often improves the cognitive functions of individuals who previously received hemodialysis, the effect of a kidney transplant on this abnormal allocation of spatial attention has not been investigated. OBJECTIVE: To investigate the effects of kidney transplant on individuals who were being treated with dialysis and had an increase in their left spatial attentional bias. METHOD: The performance of 20 hemodialyzed individuals with ESRD on the line bisection test was compared to that of 17 demographically matched individuals with ESRD, who had received a kidney transplant, and 23 demographically matched healthy controls (HC). RESULTS: All of the participants exhibited a left spatial bias on the line bisection task. When compared with the HC, the hemodialyzed individuals demonstrated a significantly greater left spatial bias. There was, however, no difference in spatial bias between the HC and the individuals who had received a kidney transplant. CONCLUSION: A successful kidney transplant can improve patients' abnormal leftward allocation of spatial attention. However, future studies are needed to better understand the mechanisms of this spatial attentional bias in hemodialyzed individuals and the normalization of bias following transplantation.

Posttraumatic Stress Disorder and Anxiety-Related Conditions.

PURPOSE OF REVIEW: This article provides a synopsis of current assessment and treatment considerations for posttraumatic stress disorder (PTSD) and related anxiety disorder characteristics. Epidemiologic and neurobiological data are reviewed as well as common associated symptoms, including sleep disruption, and treatment approaches to these conditions. RECENT FINDINGS: PTSD is no longer considered an anxiety-related disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition classification and instead is associated with trauma/stressor-related disorders. PTSD symptoms are clustered into four domains including intrusive experiences, avoidance, mood, and arousal symptoms. Despite this reclassification, similarities exist in consideration of diagnosis, treatment, and comorbidities with anxiety disorders. PTSD and anxiety-related disorders are heterogeneous, which is reflected by the neural circuits involved in the genesis of symptoms that may vary across symptom domains. Treatment is likely to benefit from consideration of this heterogeneity.Research in animal models of fear and anxiety, as well as in humans, suggests that patients with PTSD and generalized anxiety disorder have difficulty accurately determining safety from danger and struggle to suppress fear in the presence of safety cues.Empirically supported psychotherapies commonly involved exposure (fear extinction learning) and are recommended for PTSD. Cognitive-behavioral therapy has been shown to be effective in other anxiety-related disorders. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly used in the treatment of PTSD and anxiety disorders in which pharmacologic intervention is supported. Treating sleep disruption including sleep apnea (continuous positive airway pressure [CPAP]), nightmares, and insomnia (preferably via psychotherapy) may improve symptoms of PTSD, as well as improve mood in anxiety disorders. SUMMARY: PTSD has a lifetime prevalence that is close to 10% and shares neurobiological features with anxiety disorders. Anxiety disorders are the most common class of mental conditions and are highly comorbid with other disorders; treatment considerations typically include cognitive-behavioral therapy and pharmacologic intervention. Developing technologies show some promise as treatment alternatives in the future.

The Allocation of Vertical Attention in Patients with End-Stage Renal Disease Receiving Dialysis.

Objectives: Alterations of spatial attention can have adverse effects, such a greater probability of accidents. Patients with end-stage renal disease (ESRD) receiving dialysis have stronger left-sided spatial attentional bias, suggesting that this disorder or treatment alters the brain networks that mediate spatial attention. The hemispheric networks that mediate the allocation of horizontal attention may also influence the allocation of vertical attention. However, the allocation of vertical spatial attention has not been studied in ESRD patients. Methods: Twenty-three ESRD patients receiving dialysis and 23 healthy right-handed controls performed line bisections using 24 vertical lines (24 cm long and 2 mm thick) aligned with the intersection of their midsagittal and coronal planes. Results: Hemodialyzed ESRD patients had a significantly greater upward bias than healthy controls. The magnitude of this bias was correlated with the duration of the kidney disease. Conclusions: The reason why upward attentional bias is increased in hemodialyzed ESRD patients is not known. Further research is needed to better understand the brain mechanism that might account for this bias, as well as its treatment. However, hemodialyzed ESRD patients and their families-caregivers should be made aware of this disorder to avoid accidents such as tripping.

Circulating Cytokines Predict 1H-Proton MRS Cerebral Metabolites in Healthy Older Adults.

Background: Changes in both circulating cytokines and neurochemical concentrations have been observed in aging. Patterns of change across these factors are associated with age-related pathologies, including neurodegenerative disease. More evidence to define patterns of change that are characteristic of healthy aging is needed, as is an investigation into how age-related changes in blood cytokines and brain neurochemicals may relate to one another in a healthy older adult population. Methods: Single voxel 1H-proton magnetic resonance spectroscopy was collected in medial frontal and medial parietal regions. Phosphocholine and glycerophosphocholine (Cho), myo-inositol (MI), N-acetylaspertate and N-acetylasperglutamate (NAA), creatine and phosphocreatine (Cr), and glutamate and glutamine (Glx) were measured in a sample of 83 healthy, cognitively normal adults aged 52-89. Blood data were collected to quantify 12 cytokines: interleukins (IL-) 2, 5, 6, 7, 8, 10, 12, 13, IL-1 ß, tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), and IL-17 α. Correlation analyses were performed to assess age relationships between each of these factors. Backward linear regressions were performed. Cytokine data and age were used as predictors of each cerebrospinal fluid (CSF)-corrected metabolite concentration in both voxels. Results: Associations were identified between a variety of cytokines and concentrations of frontal NAA, Cr, and Glx, and of parietal MI, Cho, NAA, and Cr. In the frontal voxel, NAA was predicted by more IL-1B and less TNF-α, Cr by less TNF-α and more IL-5, and Glx by less TNF-α. In the parietal voxel, MI was predicted by more IL-10 and IL-8 and less IL-2, Cho by more TNF-α and less IL-2, NAA by more IL-1B and TNF-α and less IL-13, IL-2, and IL-7, and Cr by more IL-10 and less IL-2. Conclusions: Associations were identified between circulating cytokines and neurometabolite concentrations in this sample of older adults. The present results serve as the initial evidence of relationships between circulating cytokines and neurophysiology. Findings invite further investigation to understand the physiological consequences of aging, and how peripheral inflammatory markers may relate to neurochemical concentrations in healthy aging.

Hyperarousal symptoms and decreased right hemispheric frontolimbic white matter integrity predict poorer sleep quality in combat-exposed veterans.

OBJECTIVE: Disrupted sleep is common following combat deployment. Contributors to risk include posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI); however, the mechanisms linking PTSD, mTBI, and sleep are unclear. Both PTSD and mTBI affect frontolimbic white matter tracts, such as the uncinate fasciculus. The current study examined the relationship between PTSD symptom presentation, lateralized uncinate fasciculus integrity, and sleep quality. METHOD: Participants include 42 combat veterans with and without PTSD and mTBI. Freesurfer and Tracula were used to establish specific white matter ROI integrity via 3-T MRI. The Pittsburgh Sleep Quality Index and PTSD Checklist were used to assess sleep quality and PTSD symptoms. RESULTS: Decreased fractional anisotropy in the right uncinate fasciculus (ß = -1.11, SE = 0.47, p < .05) and increased hyperarousal symptom severity (ß = 3.50, SE = 0.86, p < .001) were associated with poorer sleep quality. CONCLUSION: Both right uncinate integrity and hyperarousal symptom severity are associated withsleep quality in combat veterans. The right uncinate is a key regulator of limbic behavior and sympathetic nervous system reactivity, a core component of hyperarousal. Damage to this pathway may be one mechanism by which mTBI and/or PTSD could create vulnerability for sleep problems following combat deployment.

Posttraumatic Stress Disorder Subsequent to Apparent Mild Traumatic Brain Injury.

Posttraumatic stress disorder (PTSD) is prevalent among veterans with a history of traumatic brain injury (TBI); however, the relationship between TBI and PTSD is not well understood. We present the case of a 31-year-old male veteran with PTSD who reported TBI before entering the military. The reported injury appeared to be mild: He was struck on the head by a baseball, losing consciousness for ∼10 seconds. Years later, he developed severe PTSD after combat exposure. He was not receiving clinical services for these issues but was encountered in the context of a research study. We conducted cognitive, autonomic, and MRI assessments to assess brain function, structure, and neurophysiology. Next, we compared amygdala volume, uncinate fasciculus diffusion, functional connectivity, facial affect recognition, and baroreceptor coherence with those of a control group of combat veterans (n = 23). Our veteran's MRI revealed a large right medial-orbital prefrontal lesion with surrounding atrophy, which the study neuroradiologist interpreted as likely caused by traumatic injury. Comparison with controls indicated disrupted structural and functional connectivity of prefrontal-limbic structures and impaired emotional, cognitive, and autonomic responses. Detection of this injury before combat would have been unlikely in a clinical context because our veteran had reported a phenomenologically mild injury, and PTSD is a simple explanation for substance abuse, sleep impairment, and psychosocial distress. However, it may be that right prefrontal-limbic disruption imparted vulnerability for the development of PTSD and exacerbated our veteran's emotional response to, and recovery from, PTSD.