Validation of a modified-composite autonomic symptom score (COMPASS-31) as an outcome measure for persistent autonomic symptoms post-concussion: an observational pilot study.

OBJECTIVE: Persistent symptoms post-mild traumatic brain injury (mTBI) includes autonomic dysregulation (AD). The composite autonomic symptoms score, (COMPASS-31), was developed to quantify AD symptom severity in the last year, which limits clinical utility. The primary aim was to determine validity of a modified-COMPASS-31 measuring symptoms in the last month compared to the original, secondarily to compare both original and modified versions to the Neurobehavioral Symptom Inventory (NSI), and tertiarily to detect change post-treatment of the modified-COMPASS-31 compared to NSI and headache intensity (HI). PARTICIPANTS: Thirty-three military personnel with persistent headache post-mTBI. MAIN OUTCOME MEASURES: Total and domain scores for COMPASS-31 (original vs. modified) NSI and HI at baseline. Change in modified-COMPASS-31. NSI, and HI. RESULTS: Baseline COMPASS-31 versions were comparable and highly correlated (r = 0.72, p < 0.001), they were moderately correlated at best to the NSI (r < 0.6), which may suggest differences in measurement metrics. The mean change in modified-COMPASS-31 scores (15.4/100, effect size 0.8) was mild to moderately correlated to the change in HI (r = 0.39) score, but not to NSI (r = 0.28). CONCLUSION: The modified-COMPASS-31 appears to be valid, can measure change of AD symptom severity, and is recommended as an outcome measure.

Grooved Pegboard adds incremental value over memory-apparent performance validity tests in predicting psychiatric symptom report.

The present study evaluated whether Grooved Pegboard (GPB), when used as a performance validity test (PVT), can incrementally predict psychiatric symptom report elevations beyond memory-apparent PVTs. Participants (N = 111) were military personnel and were predominantly White (84%), male (76%), with a mean age of 43 (SD = 12) and having on average 16 years of education (SD = 2). Individuals with disorders potentially compromising motor dexterity were excluded. Participants were administered GPB, three memory-apparent PVTs (Medical Symptom Validity Test, Non-Verbal Medical Symptom Validity Test, Reliable Digit Span), and a symptom validity test (Personality Assessment Inventory Negative Impression Management [NIM]). Results from the three memory-apparent PVTs were entered into a model for predicting NIM, where failure of two or more PVTs was categorized as evidence of non-credible responding. Hierarchical regression revealed that non-dominant hand GPB T-score incrementally predicted NIM beyond memory-apparent PVTs (F(2,108) = 16.30, p < .001; R2 change = .05, ß = -0.24, p < .01). In a second hierarchical regression, GPB performance was dichotomized into pass or fail, using T-score cutoffs (≤29 for either hand, ≤31 for both). Non-dominant hand GPB again predicted NIM beyond memory-apparent PVTs (F(2,108) = 18.75, p <.001; R2 change = .08, ß = -0.28, p < .001). Results indicated that noncredible/failing GPB performance adds incremental value over memory-apparent PVTs in predicting psychiatric symptom report.

Neurobehavioral Symptom Inventory Item-Level Change Complements the Reliable Change Method.

OBJECTIVE: To determine correspondence between the statistically derived 8-point reliable change index for the Neurobehavioral Symptom Inventory (NSI) against clinically significant item-level change in symptom severity from intake to discharge for mild traumatic brain injury (mTBI). SETTING: Brain Injury Rehabilitation Service at Brooke Army Medical Center, Fort Sam Houston, San Antonio, Texas. PATIENTS: In total, 655 active-duty service members with a diagnosis of mTBI who received treatment and completed self-report measures between 2007 and 2020. DESIGN: Observational retrospective analysis of outpatient clinical outcomes data. MAIN MEASURES: NSI total score change was used to divide patients into responder and nonresponders based on whether they met an 8-point decrease between intake and discharge. In addition, patients who had at least one NSI item that changed from a rating of 3 (severe) or 4 (very severe) at intake to a rating of 0 (none) or 1 (mild) at discharge were coded as an individual with significant item-level change. RESULTS: Forty-five percent of the sample had significant item-level change and were classified as responders according to the reliable change method. Eight percent of the sample had significant item-level change but did not meet the 8-point reliable change threshold. Fifteen percent of the sample did not experience significant item-level change but were classified as responders according to reliable change. Thirty-one percent did not meet either method's criterion for change. Classification agreement between the reliable change and item-level change methods was 76%, which was statistically significant ( = 181.32, P < .001). CONCLUSION: There is good correspondence between reliable change and item-level change on the NSI in this population. Reliable change is easily calculated and thus much more accessible than the item-level change method. There may be some situations where calculating item-level change may be helpful.

NSI and PCL-5 Normative Tables for Active Duty Service Members Affected by Traumatic Brain Injury.

INTRODUCTION: Many service members (SMs) have been diagnosed with traumatic brain injury. Currently, military treatment facilities do not have access to established normative tables which can assist clinicians in gauging and comparing patient-reported symptoms. The aim of this study is to provide average scores for both the Neurobehavioral Symptom Inventory (NSI) and Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) for active duty SMs based upon varying demographic groups. METHODS: Average scores were calculated for both the NSI and PCL-5 surveys from SMs who attended a military outpatient traumatic brain injury clinic. For this analysis, only the initial surveys for each SM were considered. The identifying demographics included age group, gender, grade, and race. RESULTS: Four normative tables were created to show the average scores of both the NSI and PCL-5 surveys grouped by demographics. The tables are grouped by Age Group/Gender/Race and Grade/Gender/Race. CONCLUSION: Clinicians and healthcare administrators can use the scores reported in this study to determine where SM NSI or PCL-5 scores fall within the average for their demographic group.

Possible autonomic or cranial nerve symptoms triggered during sustained neck rotation in persistent headache post-concussion: a retrospective observational cross-sectional study.

OBJECTIVES: To examine and categorize symptoms occurring within 60 s of vertebrobasilar-insufficiency (VBI) testing (left- and right-neck rotation) in individuals with persistent post-traumatic headache. BACKGROUND: As part of routine clinical cervical screening in our patients, we found extended VBI testing often triggered additional symptoms. Therefore, we aimed to document the prevalence and precise symptoms occurring during each movement direction of this test and determine any demographic or baseline signs or symptoms associated with a positive test. METHODS: A retrospective medical record review on military personnel receiving treatment for persistent post-traumatic headache was performed. Participants were grouped according to presence of non-headache related symptoms triggered during the tests. Frequency, onset, and symptom characteristics reported were categorized as potentially vascular and/or possible autonomic or cranial nerve in nature. RESULTS: At least one symptom was reported by 81.3% of 123 patients. Of these, 54% reported symptoms in one and 46% in both directions of rotation, yielding 146 abnormal tests. Most reported symptoms were tear disruption (41%), altered ocular-motor-control (25%), and blepharospasm (16%). Enlisted individuals and those with altered baseline facial sensation were more likely to have a positive test. CONCLUSIONS: The majority reported symptoms not typical of VBI within 60 seconds of sustained neck rotation. Further study is needed to better understand the mechanisms and clinical relevance.

Sub-occipital muscle pressure pain thresholds correlate to direction of symptomatic active comfortable sustained neck rotation testing in post-concussive headache: a retrospective observational cross-sectional study.

OBJECTIVES: To compare sub-occipital muscle pressure sub pain thresholds (PPTs) in individuals with persistent-post-traumatic-headache (PPTH) in relation to the presence or not of cranial nerve and/or autonomic symptoms reported during sustained neck rotation (SNR). BACKGROUND: Previously 81% of military service members with PPTH demonstrated symptoms with SNR up to 60 seconds. Of these, 54% reported symptoms in one (Uni-Symp) and 46% in both directions of rotation (Bi-Symp). Sub-occipital PPTs, in relation to SNR direction, were of interest. METHODS: Retrospective review of records of 77 individuals, with PPTH with both SNR and PPTs. Average suboccipital and scalene PPTs were compared between Asymptomatic (n = 13), upon SNR testing, or Symptomatic (Uni-Symp, n = 32, Bi-Symp, n = 32), groups. RESULTS: The Bi-Symp group had significantly reduced sub-occipital PPTs relative to the Asymptomatic group on both sides [p < 0.009] with no side-to-side differences in either group. The Uni-Symp group had significantly lower sub-occipital PPTs on the symptomatic SNR test direction compared to the asymptomatic side [t(31) = 3.37, p = 0.002]. There were no differences within or between groups in the scalene PPTs(p's > 0.08). CONCLUSIONS: An upper cervical mechanical trigger of symptoms during SNR tests in some individuals with PPTH is possible. The direction of symptomatic SNR tests may indicate direction of guarded hypermobile dysfunction and direct treatment.

Characteristics of Responders and Nonresponders in a Military Postconcussion Rehabilitation Program.

OBJECTIVE: To characterize treatment responders and nonresponders as measured by the Neurobehavioral Symptom Inventory (NSI) in order to understand whether certain traits in our patient population would characterize favorable response. SETTING: Brain Injury Rehabilitation Service at Brooke Army Medical Center, Fort Sam Houston, San Antonio, Texas. PATIENTS: In total, 655 active duty military patients with a diagnosis of mild traumatic brain injury (mTBI) who received treatment between 2007 and 2020 and completed self-report measures as part of routine care. DESIGN: Observational retrospective analysis of outpatient clinical outcomes data. MAIN MEASURES: The primary outcome measure was the NSI, divided into the responder and nonresponder groups. Responders were defined by reliable change in NSI total score (decrease of ≥8 points from intake to discharge). FINDINGS: Responders ( n = 395) reported a higher level of symptom burden at intake on the NSI. Women responded proportionally more (70%) than men (58%). After treatment, responders reported improvements on all measures evaluated while nonresponders reported no change or slightly worse symptoms. Logistic regression analysis showed that posttraumatic stress symptoms at intake decreased odds of favorable treatment response while satisfaction with social relationships increased odds of favorable treatment response. CONCLUSION: The results from this process improvement project suggested that posttraumatic symptoms warrant programmatic attention in TBI clinics while social relationships may be a protective factor that can be capitalized to enhance troop readiness. Systematic examination of these characteristics should be conducted on a larger population within the military health system.

Correlations Between the Neurobehavioral Symptom Inventory and Other Commonly Used Questionnaires for Traumatic Brain Injury.

OBJECTIVE: To evaluate the correlations between the Neurobehavioral Symptom Inventory (NSI) and other questionnaires commonly administered within military traumatic brain injury clinics. SETTING: Military outpatient traumatic brain injury clinics. PARTICIPANTS: In total, 15,428 active duty service members who completed 24,162 NSI questionnaires between March 2009 and May 2020. DESIGN: Observational retrospective analysis of questionnaires collected as part of standard clinical care. MAIN MEASURES: NSI, Post-Traumatic Stress Disorder Checklist for DSM-5 and Military Version, Patient Health Questionnaire (PHQ), Generalized Anxiety Disorder, Headache Impact Test (HIT-6), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Activities-Specific Balance Confidence Scale (ABC), Dizziness Handicap Inventory (DHI), Alcohol Use Disorders Identification Test (AUDIT), and the World Health Organization Quality of Life Instrument-Abbreviated Version. Only questionnaires completed on the same date as the NSI were examined. RESULTS: The total NSI score was moderately to strongly correlated with all questionnaires except for the AUDIT. The strongest correlation was between the NSI Affective Score and the PHQ9 (r = 0.86). The NSI Vestibular Score was moderately correlated with the ABC (r = -0.55) and strongly correlated with the DHI (r = 0.77). At the item level, the HIT-6 showed strong correlation with NSI headache (r = 0.80), the ISI was strongly correlated with NSI difficulty sleeping (r = 0.63), and the ESS was moderately correlated with NSI fatigue (r = 0.39). CONCLUSION: Clinicians and healthcare administrators can use the correlations reported in this study to determine if questionnaires add incremental value for their clinic as well as to make more informed decisions regarding which questionnaires to administer.

Validation of grooved pegboard cutoffs as an additional embedded measure of performance validity.

OBJECTIVE: Using embedded performance validity (PVT) comparisons, Erdodi et al. suggested that Grooved Pegboard (GPB) T-score cutoffs for either hand (≤ 29) or both hands (≤ 31) could be used as additional embedded PVTs. The current study evaluated the relationship between these proposed cutoff scores and established PVTs (Medical Symptom Validity Test [MSVT]; Non-Verbal Medical Symptom Validity Test [NV-MSVT], and Reliable Digit Span [RDS]). METHOD: Participants (N = 178) were predominately Caucasian (84%) males (79%) with a mean age and education of 41 (SD = 11.7) and 15.8 years (SD = 2.3), respectively. Participants were stratified as "passing" or "failing" the GPBviaErdodi's proposed criteria. "Failures" on the MSVT, NV-MSVT, and RDS were based on conventional recommendations. RESULTS: Moderate correlations between GPB classification and a condition of interest (COI; i.e. at least two failures on reference PVTs) were observed for dominant (χ2 (1, n = 178) = 34.72, ϕ = .44, p < .001), non-dominant (χ2 (1, n = 178) = 16.46, ϕ = .30, p = .001), and both hand conditions (χ2 (1, n = 178) = 32.48, ϕ = .43, p < .001). Sensitivity, specificity, and predictive power were generally higher than Erdodi et al.'s initial findings. CONCLUSION: These findingsprovide supportfor the clinical utility of the GPB as an additional embedded PVT. More specifically, dominant and both hand cutoffs were found to be more robust measures ofnon-genuine performance in those without motor deficits. While promising, sensitivity continues to be low; therefore, it is ill-advised to use the GPB as a sole measure of -performance validity.

Effects of cocaine and HIV on decision-making abilities.

Our study aimed to understand the impact of cocaine dependence on high-risk decision-making abilities in individuals with the human immunodeficiency virus (HIV) and individuals with cocaine dependence. We recruited 99 participants (27 HIV/Cocaine, 20 HIV Only, 26 Cocaine Only, and 26 Healthy Controls). The Iowa Gambling Task (IGT) was applied to assess decision-making abilities. Independent and interactive effects of HIV status and cocaine dependence were examined using 2 × 2 factorial ANCOVA with premorbid IQ (WRAT-4: WR) as the covariate. We found cocaine dependence had a significant adverse effect on overall IGT performance (p = 0.015). We also found individuals who were HIV-positive tended to have less total money at the end of the game than individuals who were HIV-negative (p = 0.032), suggesting individuals living with HIV had less focus on long-term gains and more focus on short-term gains. Our findings highlight the significant impact of cocaine dependence on decision-making abilities and the difficulty individuals with HIV have in adequately weighing the cost and benefits of their decisions and making appropriate changes for the future.

Single-Item Versus Multiple-Item Headache Ratings in Service Members Seeking Treatment for Brain Injury.

INTRODUCTION: Headaches are the most common complaint after traumatic brain injury (TBI) and a significant cause of morbidity and disability among military personnel. Currently, there are a several measures which can assess headache disability, but there is a significant burden to assess each individual symptom given this heterogeneous polymorbid population. The objective of this proposed study was to validate the single headache item from the Neurobehavioral Symptom Inventory (NSI) compared to the 6-item Headache Impact Test (HIT-6). MATERIALS AND METHODS: Participants included consecutive treatment-seeking outpatients at the Brain Injury Rehabilitation Service at the Brooke Army Medical Center from August 2007 to January 2010 who were administered a battery of assessment measures at initial intake, as part of usual care. Archival record review was conducted using procedures approved by the local Institutional Review Board. Inclusionary criteria included completion of both the HIT-6 and NSI. Participants with a cut-off score of >22 on the NSI Validity-10 were excluded in a post hoc analysis to validate findings among those who passed validity screen. RESULTS: The Pearson correlation between the single-item NSI headache measure and the HIT-6 revealed at least 64% shared variance in this military sample (r = 0.8, p < 0.001), indication a high association between the two measures. CONCLUSION: The NSI single-item headache measure adequately captured headache severity in this military cohort. Use of the single-item NSI headache measure may minimize survey burden on participants whose primary complaint is not headaches, or who present with multiple symptoms. Future studies are needed to validate the single-item headache measure in other samples.

Sleep problems contribute to post-concussive symptoms in service members with a history of mild traumatic brain injury without posttraumatic stress disorder or major depressive disorder.

BACKGROUND: Many with a history of mild traumatic brain injury (TBI) experience sleep problems, which are also common symptoms of stress-related and mood disorders. OBJECTIVE: To determine if sleep problems contributed unique variance to post-concussive symptoms above and beyond symptoms of posttraumatic stress disorder/major depressive disorder (PTSD/MDD) after mild TBI. METHODS: 313 active duty service members with a history of mild TBI completed sleep, PTSD, and mood symptom questionnaires, which were used to determine contributions to the Neurobehavioral Symptom Inventory. RESULTS: 59% of the variance in post-concussive symptoms were due to PTSD symptom severity while depressive symptoms and sleep problems contributed an additional 1% each. This pattern differed between those with and without clinical diagnosis of PTSD/MDD. For those with PTSD/MDD, PTSD and depression symptoms but not sleep contributed to post-concussive symptoms. For those without PTSD/MDD, PTSD symptoms and sleep contributed specifically to somatosensory post-concussive symptoms. Daytime dysfunction and sleep disturbances were associated with post-concussive symptoms after PTSD and depression symptoms were controlled. CONCLUSIONS: PTSD symptom severity explained the most variance for post-concussive symptoms among service members with a history of mild TBI, while depression symptoms, daytime dysfunction, and sleep disturbances independently contributed small amounts of variance.

Correlates of Depression in U.S. Military Service Members With a History of Mild Traumatic Brain Injury.

OBJECTIVES: Post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) are identified as signature injuries of the Wars in Iraq and Afghanistan. Statistics have confirmed a high incidence of PTSD among military personnel with mild TBI (mTBI) who served in these conflicts. Although receiving less attention, individuals with a history of mTBI are also at increased risk for depressive disorders. This study examines the incidence and correlates of depression in service members with a history of mTBI received an average of 4-1/2 years prior to evaluation. METHODS: Retrospective analysis of 184 service members with a history of mTBI extracted from a data repository maintained at a military medical center. RESULTS: One-third of the sample (34.2%) was clinically diagnosed with a depressive disorder in the month preceding evaluation. Of those with depression, 81% (51 of 63) were also diagnosed with PTSD. Proportionately more women than men had depression. Depression was more common among those who were undergoing a Military Evaluation Board and those who served in more than three combat deployments. CONCLUSIONS: Results confirm chronically elevated the rates of depressive disorders and PTSD comorbidity among service members with a history of mTBI. Depression screening and treatment within the Military Health System should remain a priority for service members reporting a remote history of mTBI. Individuals with chronic PTSD, women, service members undergoing MEB and those who served in greater than three combat deployments are at particular risk.

Symptom Reporting Patterns of US Military Service Members with a History of Concussion According to Duty Status.

OBJECTIVE: To compare symptom reporting patterns of service members with a history of concussion based on work status: full duty, limited duty, or in the Medical Evaluation Board (MEB)/disability process. METHODS: Retrospective analysis of 181 service members with a history of concussion (MEB n = 56; limited duty n = 62; full duty n = 63). Neurobehavioral Symptom Inventory (NSI) Validity-10 cutoff (>22) and Mild Brain Injury Atypical Symptoms Scale (mBIAS) cutoffs (≥10 and ≥8) were used to evaluate potential over-reporting of symptoms. RESULTS: The MEB group displayed significantly higher NSI scores and significantly higher proportion scored above the mBIAS ≥10 cutoff (MEB = 15%; limited duty = 3%; full duty = 5%). Validity-10 cutoff did not distinguish between groups. CONCLUSIONS: MEB but not limited duty status was associated with increased risk of over-reporting symptoms in service members with a history of concussion. Results support the use of screening measures for over-reporting in the MEB/disability samples.

Adversity and Resilience Are Associated with Outcome after Mild Traumatic Brain Injury in Military Service Members.

The objective of this study was to assess the associations between resilience, adversity, post-concussion symptoms, and post-traumatic stress symptom reporting after mild traumatic brain injury (mTBI). We hypothesized that resilience would be associated with less symptom reporting, and adversity would be associated with greater symptom reporting. This was a cross-sectional study of retrospective data collected for an ongoing TBI repository. United States military service members who screened positive for mTBI during a primary care visit completed the Trauma History Screen (THS), Connor-Davidson Resilience Scale (CD-RISC), Neurobehavioral Symptom Inventory (NSI), and post-traumatic stress disorder (PTSD) Checklist-Civilian Version (PCL-C). Data collected from February 2015 to August 2016 were used for the present study. Only participants with complete data for the above measures were included, yielding a sample size of 165 participants. Adversity (THS) and resilience (CD-RISC) scores were each correlated significantly with post-concussion (NSI) and traumatic stress (PCL-C) total and subscale scores in the hypothesized direction. Interactions between adversity and resilience were absent for all measures except the NSI sensory subscale. Four traumatic event types were significantly associated positively with most NSI and PCL-C total and subscale scores, but the age at which traumatic events were first experienced showed few and mixed significant associations. In conclusion, resilience and adversity were significantly associated with symptom endorsement after mTBI. Screening for cumulative adversity may identify individuals at greater risk of developing persistent post-concussion symptoms and/or PTSD, and interventions that increase resilience may reduce symptom severity.

Effects of Delay Duration on the WMS Logical Memory Performance of Older Adults with Probable Alzheimer's Disease, Probable Vascular Dementia, and Normal Cognition.

OBJECTIVE: To examine how the duration of time delay between Wechsler Memory Scale (WMS) Logical Memory I and Logical Memory II (LM) affected participants' recall performance. METHOD: There are 46,146 total Logical Memory administrations to participants diagnosed with either Alzheimer's disease (AD), vascular dementia (VaD), or normal cognition in the National Alzheimer's Disease Coordinating Center's Uniform Data Set. RESULTS: Only 50% of the sample was administered the standard 20-35 min of delay as specified by WMS-R and WMS-III. We found a significant effect of delay time duration on proportion of information retained for the VaD group compared to its control group, which remained after adding LMI raw score as a covariate. There was poorer retention of information with longer delay for this group. This association was not as strong for the AD and cognitively normal groups. A 24.5-min delay was most optimal for differentiating AD from VaD participants (47.7% classification accuracy), an 18.5-min delay was most optimal for differentiating AD versus normal participants (51.7% classification accuracy), and a 22.5-min delay was most optimal for differentiating VaD versus normal participants (52.9% classification accuracy). CONCLUSIONS: Considering diagnostic implications, our findings suggest that test administration should incorporate precise tracking of delay periods. We recommend a 20-min delay with 18-25-min range. Poor classification accuracy based on LM data alone is a reminder that story memory performance is only one piece of data that contributes to complex clinical decisions. However, strict adherence to the recommended range yields optimal data for diagnostic decisions.

Age-related changes in amygdala-frontal connectivity during emotional face processing from childhood into young adulthood.

The ability to process and respond to emotional facial expressions is a critical skill for healthy social and emotional development. There has been growing interest in understanding the neural circuitry underlying development of emotional processing, with previous research implicating functional connectivity between amygdala and frontal regions. However, existing work has focused on threatening emotional faces, raising questions regarding the extent to which these developmental patterns are specific to threat or to emotional face processing more broadly. In the current study, we examined age-related changes in brain activity and amygdala functional connectivity during an fMRI emotional face matching task (including angry, fearful, and happy faces) in 61 healthy subjects aged 7-25 years. We found age-related decreases in ventral medial prefrontal cortex activity in response to happy faces but not to angry or fearful faces, and an age-related change (shifting from positive to negative correlation) in amygdala-anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) functional connectivity to all emotional faces. Specifically, positive correlations between amygdala and ACC/mPFC in children changed to negative correlations in adults, which may suggest early emergence of bottom-up amygdala excitatory signaling to ACC/mPFC in children and later development of top-down inhibitory control of ACC/mPFC over amygdala in adults. Age-related changes in amygdala-ACC/mPFC connectivity did not vary for processing of different facial emotions, suggesting changes in amygdala-ACC/mPFC connectivity may underlie development of broad emotional processing, rather than threat-specific processing. Hum Brain Mapp 37:1684-1695, 2016. © 2016 Wiley Periodicals, Inc.

Development of superficial white matter and its structural interplay with cortical gray matter in children and adolescents.

Healthy human brain undergoes significant changes during development. The developmental trajectory of superficial white matter (SWM) is less understood relative to cortical gray matter (GM) and deep white matter. In this study, a multimodal imaging strategy was applied to vertexwise map SWM microstructure and cortical thickness to characterize their developmental pattern and elucidate SWM-GM associations in children and adolescents. Microscopic changes in SWM were evaluated with water diffusion parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in 133 healthy subjects aged 10-18 years. Results demonstrated distinct maturational patterns in SWM and GM. SWM showed increasing FA and decreasing MD and RD underneath bilateral motor sensory cortices and superior temporal auditory cortex, suggesting increasing myelination. A second developmental pattern in SWM was increasing FA and AD in bilateral orbitofrontal regions and insula, suggesting improved axonal coherence. These SWM patterns diverge from the more widespread GM maturation, suggesting that cortical thickness changes in adolescence are not explained by the encroachment of SWM myelin into the GM-WM boundary. Interestingly, age-independent intrinsic association between SWM and cortical GM seems to follow functional organization of polymodal and unimodal brain regions. Unimodal sensory areas showed positive correlation between GM thickness and FA whereas polymodal regions showed negative correlation. Axonal coherence and differences in interstitial neuron composition between unimodal and polymodal regions may account for these SWM-GM association patterns. Intrinsic SWM-GM relationships unveiled by neuroimaging in vivo can be useful for examining psychiatric disorders with known WM/GM disturbances.

Altered affective, executive and sensorimotor resting state networks in patients with pediatric mania.

BACKGROUND: The aim of the present study was to map the pathophysiology of resting state functional connectivity accompanying structural and functional abnormalities in children with bipolar disorder. METHODS: Children with bipolar disorder and demographically matched healthy controls underwent resting-state functional magnetic resonance imaging. A model-free independent component analysis was performed to identify intrinsically interconnected networks. RESULTS: We included 34 children with bipolar disorder and 40 controls in our analysis. Three distinct resting state networks corresponding to affective, executive and sensorimotor functions emerged as being significantly different between the pediatric bipolar disorder (PBD) and control groups. All 3 networks showed hyperconnectivity in the PBD relative to the control group. Specifically, the connectivity of the dorsal anterior cingulate cortex (ACC) differentiated the PBD from the control group in both the affective and the executive networks. Exploratory analysis suggests that greater connectivity of the right amygdala within the affective network is associated with better executive function in children with bipolar disorder, but not in controls. LIMITATIONS: Unique clinical characteristics of the study sample allowed us to evaluate the pathophysiology of resting state connectivity at an early state of PBD, which led to the lack of generalizability in terms of comorbid disorders existing in a typical PBD population. CONCLUSION: Abnormally engaged resting state affective, executive and sensorimotor networks observed in children with bipolar disorder may reflect a biological context in which abnormal task-based brain activity can occur. Dual engagement of the dorsal ACC in affective and executive networks supports the neuroanatomical interface of these networks, and the amygdala's engagement in moderating executive function illustrates the intricate interplay of these neural operations at rest.

Time course of recovery showing initial prefrontal cortex changes at 16 weeks, extending to subcortical changes by 3 years in pediatric bipolar disorder.

OBJECTIVE: Activation changes at the interface of affective and cognitive systems are examined over a 3 year period in pediatric bipolar disorder (PBD). METHODS: Thirteen participants with PBD and 10 healthy controls (HC) matched on demographics and IQ were scanned at baseline, at 16 weeks, and after 3 years. All patients received pharmacotherapy based on a medication algorithm. A pediatric affective color matching paradigm was used to probe cognitive processing under emotional challenge. RESULTS: At baseline, in response to emotional vs. neutral words, patients with PBD showed greater activation than HC in the right dorsal lateral prefrontal cortex (DLPFC) and amygdala, ventral lateral prefrontal cortex (VLPFC), bilateral anterior cingulate cortex (ACC), and ventral striatum. Increased activation in DLPFC in the PBD group normalized by 16 weeks. By 3 years, normalization was observed in VLPFC, ACC, amygdala, and striatum. LIMITATIONS: Small sample size renders the present findings preliminary. CONCLUSIONS: Greater activation in fronto-striatal and fronto-limbic circuits were observed in unmedicated patients with PBD. Present findings suggest the possibility that DLPFC is most malleable to pharmacological intervention with systematic pharmacotherapy leading to immediate response, which extended to amygdalostriatal and ventral cortical regions at 3 years. The seminal observation from this study is the prolonged length of recovery time in the normalization of subcortical activity along with their interfacing cortical regions. Findings from this proof of concept study need to be replicated in a larger sample.