Effect of scanning duration and sample size on reliability in resting state fMRI dynamic causal modeling analysis.

Despite its widespread use, resting-state functional magnetic resonance imaging (rsfMRI) has been criticized for low test-retest reliability. To improve reliability, researchers have recommended using extended scanning durations, increased sample size, and advanced brain connectivity techniques. However, longer scanning runs and larger sample sizes may come with practical challenges and burdens, especially in rare populations. Here we tested if an advanced brain connectivity technique, dynamic causal modeling (DCM), can improve reliability of fMRI effective connectivity (EC) metrics to acceptable levels without extremely long run durations or extremely large samples. Specifically, we employed DCM for EC analysis on rsfMRI data from the Human Connectome Project. To avoid bias, we assessed four distinct DCMs and gradually increased sample sizes in a randomized manner across ten permutations. We employed pseudo true positive and pseudo false positive rates to assess the efficacy of shorter run durations (3.6, 7.2, 10.8, 14.4 min) in replicating the outcomes of the longest scanning duration (28.8 min) when the sample size was fixed at the largest (n = 160 subjects). Similarly, we assessed the efficacy of smaller sample sizes (n = 10, 20, …, 150 subjects) in replicating the outcomes of the largest sample (n = 160 subjects) when the scanning duration was fixed at the longest (28.8 min). Our results revealed that the pseudo false positive rate was below 0.05 for all the analyses. After the scanning duration reached 10.8 min, which yielded a pseudo true positive rate of 92%, further extensions in run time showed no improvements in pseudo true positive rate. Expanding the sample size led to enhanced pseudo true positive rate outcomes, with a plateau at n = 70 subjects for the targeted top one-half of the largest ECs in the reference sample, regardless of whether the longest run duration (28.8 min) or the viable run duration (10.8 min) was employed. Encouragingly, smaller sample sizes exhibited pseudo true positive rates of approximately 80% for n = 20, and 90% for n = 40 subjects. These data suggest that advanced DCM analysis may be a viable option to attain reliable metrics of EC when larger sample sizes or run times are not feasible.

Functional brain connectivity and cortical thickness in relation to chronic pain in post-911 veterans and service members with mTBI.

OBJECTIVES: Investigate the relation of chronic pain interference to functional connectivity (FC) of brain regions and to cortical thickness in post-911 Veterans and Service Members (SMs) who sustained a mild traumatic brain injury (mTBI). METHODS: This is an observational study with cross-sectional analyses. A sample of 65 enrollees completing initial evaluation at a single site of the Chronic Effects of Neurotrauma Consortium (CENC) reported pain interference ratings on the TBI QOL. Functional connectivity and cortical thickness were measured. RESULTS: Severity of pain interference was negatively related to FC of the default mode network (DMN), i.e., participants who reported more severe pain interference had less FC between mesial prefrontal cortex and posterior regions of the DMN including posterior cingulate cortex and precuneus. Cortical thickness of specific regions was positively related to severity of pain interference. CONCLUSION: The more that pain was perceived to interfere with daily life, the less the FC between regions in a network associated with self-referential thought and mind wandering. Although cortical thickness in specific brain regions was positively related to severity of pain interference, follow-up longitudinal data, control group data, and study of individual differences in this cohort will expand this initial report and replicate these findings.

Novel fMRI working memory paradigm accurately detects cognitive impairment in multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) cannot be diagnosed by magnetic resonance imaging (MRI). Functional magnetic resonance imaging (fMRI) paradigms, such as the immediate/delayed memory task (I/DMT), detect varying degrees of working memory (WM). Preliminary findings using I/DMT showed differences in blood oxygenation level dependent (BOLD) activation between impaired (MSCI, n = 12) and non-impaired (MSNI, n = 9) multiple sclerosis (MS) patients. OBJECTIVES: The aim of the study was to confirm CI detection based on I/DMT BOLD activation in a larger cohort of MS patients. The role of T2 lesion volume (LV) and Expanded Disability Status Scale (EDSS) in magnitude of BOLD signal was also sought. METHODS: A total of 50 patients (EDSS mean ( m) = 3.2, disease duration (DD) m = 12 years, and age m = 40 years) underwent the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) and I/DMT. Working memory activation (WMa) represents BOLD signal during DMT minus signal during IMT. CI was based on MACFIMS. RESULTS: A total of 10 MSNI, 30 MSCI, and 4 borderline patients were included in the analyses. Analysis of variance (ANOVA) showed MSNI had significantly greater WMa than MSCI, in the left prefrontal cortex and left supplementary motor area ( p = 0.032). Regression analysis showed significant inverse correlations between WMa and T2 LV/EDSS in similar areas ( p = 0.005, 0.004, respectively). CONCLUSION: I/DMT-based BOLD activation detects CI in MS. Larger studies are needed to confirm these findings.

Stochastic dynamic causal modeling of working memory connections in cocaine dependence.

Although reduced working memory brain activation has been reported in several brain regions of cocaine-dependent subjects compared with controls, very little is known about whether there is altered connectivity of working memory pathways in cocaine dependence. This study addresses this issue by using functional magnetic resonance imaging-based stochastic dynamic causal modeling (DCM) analysis to study the effective connectivity of 19 cocaine-dependent subjects and 14 healthy controls while performing a working memory task. Stochastic DCM is an advanced method that has recently been implemented in SPM8 that can obtain improved estimates, relative to deterministic DCM, of hidden neuronal causes before convolution with the hemodynamic response. Thus, stochastic DCM may be less influenced by the confounding effects of variations in blood oxygen level-dependent response caused by disease or drugs. Based on the significant regional activation common to both groups and consistent with previous working memory activation studies, seven regions of interest were chosen as nodes for DCM analyses. Bayesian family level inference, Bayesian model selection analyses, and Bayesian model averaging (BMA) were conducted. BMA showed that the cocaine-dependent subjects had large differences compared with the control subjects in the strengths of prefrontal-striatal modulatory (B matrix) DCM parameters. These findings are consistent with altered cortical-striatal networks that may be related to reduced dopamine function in cocaine dependence. As far as we are aware, this is the first between-group DCM study using stochastic methodology.

How functional connectivity between emotion regulation structures can be disrupted: preliminary evidence from adolescents with moderate to severe traumatic brain injury.

Outcome of moderate to severe traumatic brain injury (TBI) includes impaired emotion regulation. Emotion regulation has been associated with amygdala and rostral anterior cingulate (rACC). However, functional connectivity between the two structures after injury has not been reported. A preliminary examination of functional connectivity of rACC and right amygdala was conducted in adolescents 2 to 3 years after moderate to severe TBI and in typically developing (TD)control adolescents, with the hypothesis that the TBI adolescents would demonstrate altered functional connectivity in the two regions. Functional connectivity was determined by correlating fluctuations in the blood oxygen level dependent(BOLD) signal of the rACC and right amygdala with that of other brain regions. In the TBI adolescents, the rACC was found to be significantly less functionally connected to medial prefrontal cortices and to right temporal regions near the amygdala (height threshold T = 2.5, cluster level p < .05, FDR corrected), while the right amygdala showed a trend in reduced functional connectivity with the rACC (height threshold T = 2.5, cluster level p = .06, FDR corrected). Data suggest disrupted functional connectivity in emotion regulation regions. Limitations include small sample sizes. Studies with larger sample sizes are necessary to characterize the persistent neural damage resulting from moderate to severe TBI during development.

Executive control network resting state fMRI functional and effective connectivity and delay discounting in cocaine dependent subjects compared to healthy controls.

Resting state functional magnetic resonance imaging (fMRI) has been used to study functional connectivity of brain networks in addictions. However, most studies to-date have focused on the default mode network (DMN) with fewer studies assessing the executive control network (ECN) and salience network (SN), despite well-documented cognitive executive behavioral deficits in addictions. The present study assessed the functional and effective connectivity of the ECN, DMN, and SN in cocaine dependent subjects (CD) (n = 22) compared to healthy control subjects (HC) (n = 22) matched on age and education. This study also investigated the relationship between impulsivity measured by delay discounting and functional and effective connectivity of the ECN, DMN, and SN. The Left ECN (LECN), Right ECN (RECN), DMN, and SN functional networks were identified using FSL MELODIC independent component analysis. Functional connectivity differences between CD and HC were assessed using FSL Dual Regression analysis and FSLNets. Effective connectivity differences between CD and HC were measured using the Parametric Empirical Bayes module of Dynamic Causal Modeling. The relationship between delay discounting and functional and effective connectivity were examined using regression analyses. Dynamic causal modeling (DCM) analysis showed strong evidence (posterior probability > 0.95) for CD to have greater effective connectivity than HC in the RECN to LECN pathway when tobacco use was included as a factor in the model. DCM analysis showed strong evidence for a positive association between delay discounting and effective connectivity for the RECN to LECN pathway and for the DMN to DMN self-connection. There was strong evidence for a negative association between delay discounting and effective connectivity for the DMN to RECN pathway and for the SN to DMN pathway. Results also showed strong evidence for a negative association between delay discounting and effective connectivity for the RECN to SN pathway in CD but a positive association in HC. These novel findings provide preliminary support that RECN effective connectivity may differ between CD and HC after controlling for tobacco use. RECN effective connectivity may also relate to tobacco use and impulsivity as measured by delay discounting.

Association of Cerebral Hemodynamics and Anemia on Processing Speed in Adults with Sickle Cell Disease.

Background and Purpose: Compared to healthy controls, adult patients with Sickle Cell Disease (SCD) are anemic, and therefore have higher cardiac output and Cerebral Blood Flow (CBF) to maintain brain oxygenation. They also demonstrate comparatively more cognitive deficits due to either overt strokes or silent cerebral ischemia. However, there are few correlative studies between CBF and cognitive deficits, specifically processing speed in SCD. Such studies are important to develop biomarkers of central brain processing and ischemia for diagnosis, prognosis, and evaluating the effectiveness of potential interventions. This pilot cross-sectional study tested the hypotheses that adults with SCD and elevated CBF demonstrate lower central brain processing speed than controls on average and that CBF is inversely correlated with processing speed. Methods: We conducted a pilot cross-sectional study to assess the relation-ships between CBF, central brain processing speed, and hemoglobin levels in asymptomatic adults with SCD and controls from an urban academic medical center. MRI acquisitions at 3T consisted of 2D phase-contrast quantitative arteriograms (Qflow) of the bilateral internal carotid and vertebral arteries and 3D pseudo-continuous arterial spin labeling (pCASL) of the brain. Participants were patients with SCD (hemoglobin [Hb]SS, [Hb] SBetaThal°, or [Hb]SC) aged 22-52 years of African American descent (N=7) or community controls (Hb AA) (n=3). Processing speed was assessed as an in-direct functional marker of ischemia using a recommended test from the NIH Toolbox for Assessment of Neurological and Behavioral Function, the Pattern Comparison Processing Speed Test. t-tests were used to compare means of CBF, hemoglobin, and cognition between SCD patients and healthy controls. Among SCD patients only multivariate correla-tions were used to evaluate relationships between brain perfusion in specific brain regions vs. processing speed and CBF. The significance level was set at p≤0.05. Results: Adults with SCD reported higher CBF compared to healthy con-trols (72.15±28.90 vs. 47.23±12.30 ml/min/100g, p=0.04), and lower hemoglobin concentration (8.64±2.33 vs. 13.33±0.58, p=0.001). Heart rate in SCD patients was higher than in controls (86.29±1.37 vs. 74.00±2.10, p=0.04). Patients with SCD demonstrated lower processing speed (96.14±21.04 vs.123±13.74, p=0.02) than controls. Among adult patients with SCD, perfusion in specific regions of the brain showed an inverse relationship with processing speed, as did whole-brain CBF (p=0.0325). Conclusion: These findings, although from a small sample, lend a degree of validity to the claim that processing speed is slower in people with SCD than in controls and that CBF is significantly higher in SCD patients com-pared to controls. The results also lend credence to the finding that the degree of processing speed deficiencies among adults with SCD is correlated with the degree of elevated CBF, which is known to correspond with the degree of anemia associated with SCD.

Chronic Cocaine Use and White Matter Coherence: A Diffusion Tensor Imaging Study.

OBJECTIVE: Chronic substance use and its effects on brain function and structure has long been of interest to clinicians and researchers. Prior cross-sectional comparisons of diffusion tensor imaging (DTI) metrics have suggested deleterious effects of chronic substance use (i.e., cocaine use) on white matter coherence. However, it is unclear how these effects may replicate across geographic regions when examined with similar technologies. In this study, we sought to conduct a replication of previous work in this area and determine whether there are any patterns of persistent differences in white matter microstructure between individuals with a history of cocaine use disorder (CocUD, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and healthy controls. METHOD: A total of 46 participants (21 healthy controls, 25 chronic cocaine users) were recruited from the Richmond, Virginia metropolitan area. Information regarding past and current substance use was collected from all participants. Participants also completed structural and DTI scans. RESULTS: Consistent with previous DTI studies, significant differences were found between fractional anisotropy (FA) and axial diffusivity (AD) CocUD and controls, with CocUD showing lower FA and AD in the right inferior and superior longitudinal fasciculus, the genu, body, and splenium of the corpus callosum, and the anterior, posterior, and superior corona radiata, among several other regions. These differences were not significant for other diffusivity metrics. Lifetime alcohol consumption was greater in the CocUD group, but lifetime alcohol consumption did not show a significant linear relationship with any of the DTI metrics in within-group regression analyses. CONCLUSIONS: These data align with previously reported declines in white matter coherence in chronic cocaine users. However, it is less clear whether comorbid alcohol consumption results in an additive deleterious effect on white matter microstructure.

Subcortical functional connectivity and its association with walking performance following deployment related mild TBI.

Introduction: The relation between traumatic brain injury (TBI), its acute and chronic symptoms, and the potential for remote neurodegenerative disease is a priority for military research. Structural and functional connectivity (FC) of the basal ganglia, involved in motor tasks such as walking, are altered in some samples of Service Members and Veterans with TBI, but any behavioral implications are unclear and could further depend on the context in which the TBI occurred. Methods: In this study, FC from caudate and pallidum seeds was measured in Service Members and Veterans with a history of mild TBI that occurred during combat deployment, Service Members and Veterans whose mild TBI occurred outside of deployment, and Service Members and Veterans who had no lifetime history of TBI. Results: FC patterns differed for the two contextual types of mild TBI. Service Members and Veterans with deployment-related mild TBI demonstrated increased FC between the right caudate and lateral occipital regions relative to both the non-deployment mild TBI and TBI-negative groups. When evaluating the association between FC from the caudate and gait, the non-deployment mild TBI group showed a significant positive relationship between walking time and FC with the frontal pole, implicated in navigational planning, whereas the deployment-related mild TBI group trended towards a greater negative association between walking time and FC within the occipital lobes, associated with visuo-spatial processing during navigation. Discussion: These findings have implications for elucidating subtle motor disruption in Service Members and Veterans with deployment-related mild TBI. Possible implications for future walking performance are discussed.

Working memory load modulation of parieto-frontal connections: evidence from dynamic causal modeling.

Previous neuroimaging studies have shown that working memory load has marked effects on regional neural activation. However, the mechanism through which working memory load modulates brain connectivity is still unclear. In this study, this issue was addressed using dynamic causal modeling (DCM) based on functional magnetic resonance imaging (fMRI) data. Eighteen normal healthy subjects were scanned while they performed a working memory task with variable memory load, as parameterized by two levels of memory delay and three levels of digit load (number of digits presented in each visual stimulus). Eight regions of interest, i.e., bilateral middle frontal gyrus (MFG), anterior cingulate cortex (ACC), inferior frontal cortex (IFC), and posterior parietal cortex (PPC), were chosen for DCM analyses. Analysis of the behavioral data during the fMRI scan revealed that accuracy decreased as digit load increased. Bayesian inference on model structure indicated that a bilinear DCM in which memory delay was the driving input to bilateral PPC and in which digit load modulated several parieto-frontal connections was the optimal model. Analysis of model parameters showed that higher digit load enhanced connection from L PPC to L IFC, and lower digit load inhibited connection from R PPC to L ACC. These findings suggest that working memory load modulates brain connectivity in a parieto-frontal network, and may reflect altered neuronal processes, e.g., information processing or error monitoring, with the change in working memory load. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

Altered brain activation in military personnel with one or more traumatic brain injuries following blast.

Explosive blast is a frequent cause of traumatic brain injury (TBI) among personnel deployed to Afghanistan and Iraq. Functional magnetic resonance imaging (fMRI) with an event-related stimulus-response compatibility task was used to compare 15 subjects with mild, chronic blast-related TBI with 15 subjects who had not experienced a TBI or blast exposure during deployment. Six TBI subjects reported multiple injuries. Relative to the control group, TBI subjects had slightly slower responses during fMRI and increased somatic complaints and symptoms of post-traumatic stress disorder (PTSD) and depression. A between-group analysis indicated greater activation during stimulus-response incompatibility in TBI subjects within the anterior cingulate gyrus, medial frontal cortex, and posterior cerebral areas involved in visual and visual-spatial functions. This activation pattern was more extensive after statistically controlling for reaction time and symptoms of PTSD and depression. There was also a negative relationship between symptoms of PTSD and activation within posterior brain regions. These results provide evidence for increased task-related activation following mild, blast-related TBI and additional changes associated with emotional symptoms. Limitations of this study include no matching for combat exposure and different recruitment strategies so that the control group was largely a community-based sample, while many TBI subjects were seeking services.

Criminal conviction, impulsivity, and course of illness in bipolar disorder.

OBJECTIVE: Criminal behavior in bipolar disorder may be related to substance use disorders, personality disorders, or other comorbidities potentially related to impulsivity. We investigated relationships among impulsivity, antisocial personality disorder (ASPD) or borderline personality disorder symptoms, substance use disorder, course of illness, and history of criminal behavior in bipolar disorder. METHODS: A total of 112 subjects with bipolar disorder were recruited from the community. Diagnosis was by Structured Clinical Interview for DSM-IV (SCID-I and SCID-II); psychiatric symptom assessment by the Change version of the Schedule for Affective Disorders and Schizophrenia (SADS-C); severity of Axis II symptoms by ASPD and borderline personality disorder SCID-II symptoms; and impulsivity by questionnaire and response inhibition measures. RESULTS: A total of 29 subjects self-reported histories of criminal conviction. Compared to other subjects, those with convictions had more ASPD symptoms, less education, more substance use disorder, more suicide attempt history, and a more recurrent course with propensity toward mania. They had increased impulsivity as reflected by impaired response inhibition, but did not differ in questionnaire-measured impulsivity. On logit analysis, impaired response inhibition and ASPD symptoms, but not substance use disorder, were significantly associated with criminal history. Subjects convicted for violent crimes were not more impulsive than those convicted for nonviolent crimes. CONCLUSIONS: In this community sample, a self-reported history of criminal behavior is related to ASPD symptoms, a recurrent and predominately manic course of illness, and impaired response inhibition in bipolar disorder, independent of current clinical state.

Dynamic Causal Modeling Self-Connectivity Findings in the Functional Magnetic Resonance Imaging Neuropsychiatric Literature.

Dynamic causal modeling (DCM) is a method for analyzing functional magnetic resonance imaging (fMRI) and other functional neuroimaging data that provides information about directionality of connectivity between brain regions. A review of the neuropsychiatric fMRI DCM literature suggests that there may be a historical trend to under-report self-connectivity (within brain regions) compared to between brain region connectivity findings. These findings are an integral part of the neurologic model represented by DCM and serve an important neurobiological function in regulating excitatory and inhibitory activity between regions. We reviewed the literature on the topic as well as the past 13 years of available neuropsychiatric DCM literature to find an increasing (but still, perhaps, and inadequate) trend in reporting these results. The focus of this review is fMRI as the majority of published DCM studies utilized fMRI and the interpretation of the self-connectivity findings may vary across imaging methodologies. About 25% of articles published between 2007 and 2019 made any mention of self-connectivity findings. We recommend increased attention toward the inclusion and interpretation of self-connectivity findings in DCM analyses in the neuropsychiatric literature, particularly in forthcoming effective connectivity studies of substance use disorders.

Preliminary Findings of Weaker Executive Control Network Resting State fMRI Functional Connectivity in Opioid Use Disorder compared to Healthy Controls.

Objective: Resting state functional magnetic resonance imaging (fMRI) functional connectivity has been used as a tool to study brain mechanisms associated with addictions. Recent research in substance use disorders has focused on three brain networks termed the default mode network (DMN), salience network (SN), and executive control network (ECN). The purpose of this study was to examine the functional connectivity of those three networks in opioid use disorder (OUD) subjects compared to healthy control subjects (HC). Methods: The present study investigated functional connectivity differences between OUD subjects compared to HC using independent component analysis. This study also examined the relationship between functional connectivity and negative urgency scores, as well as compared the functional connectivity of severe OUD to mild or moderate OUD. Results: In OUD subjects (n=25) compared to HC (n=25), a cluster in the left dorsolateral prefrontal cortex within the left ECN had significantly weaker functional connectivity. No significant differences were found between groups for the functional connectivity of the DMN, SN, or right ECN. No significant associations were found between functional connectivity and negative urgency, and no differences were found between severe OUD and mild or moderate OUD. Conclusion: These novel preliminary results suggest that ECN functional connectivity may differ between OUD and HC. This finding is consistent with previous research showing altered executive function in OUD and supports further examination of ECN functional connectivity in association with treatment response in OUD. Given our relatively small sample size (50 subjects total; 25 subjects per group), our results should be treated as preliminary for hypothesis generation, and replication will be needed in future studies.

Resting-State Directional Connectivity and Anxiety and Depression Symptoms in Adult Cannabis Users.

BACKGROUND: Anxiety and depression symptoms are common among cannabis users and could be a risk factor for cannabis use (CU) disorder. Thus, it is critical to understand the neuronal circuits underlying the associations between CU and these symptoms. Alterations in resting-state functional connectivity within and/or between the default mode network and salience network have been reported in CU, anxiety, and depressive disorders and thus could be a mechanism underlying the associations between CU disorder and anxiety/depression symptoms. METHODS: Using resting-state functional magnetic resonance imaging, effective connectivities (ECs) among 9 major nodes from the default mode network and salience network were measured using dynamic causal modeling in 2 datasets: the Human Connectome Project (28 CU participants and 28 matched non-drug-using control participants) and a local CU study (21 CU participants and 21 matched non-drug-using control participants) in separate and parallel analyses. RESULTS: Relative to the control participants, right amygdala to left amygdala, anterior cingulate cortex to left amygdala, and medial prefrontal cortex to right insula ECs were greater, and left insula to left amygdala EC was smaller in the CU group. Each of these ECs showed a reliable linear relationship with at least one of the anxiety/depression measures. Most findings on the right amygdala to left amygdala EC were common to both datasets. CONCLUSIONS: Right amygdala to left amygdala and anterior cingulate cortex to left amygdala ECs may be related to the close associations between CU and anxiety/depression symptoms. The findings on the medial prefrontal cortex to right insula and left insula to left amygdala ECs may reflect a compensatory mechanism.

Working memory fMRI activation in cocaine-dependent subjects: association with treatment response.

Functional magnetic resonance imaging (fMRI) studies of early abstinence cocaine users offer information about the state of the brain when most cocaine users seek treatment. This study examined the relationship between pretreatment brain function and subsequent treatment response in 19 treatment-seeking early abstinence cocaine-dependent (CD) subjects. These subjects and 14 non-drug-using control subjects underwent fMRI while performing a working memory task with three levels of difficulty. CD subjects were then randomized to treatment studies. Results showed CD subjects had significantly lower (random effects, corrected for multiple comparisons) brain activation in caudate, putamen, cingulate gyrus, middle and superior frontal gyri, inferior frontal gyrus pars triangularis and pars opercularis, precentral gyrus, and thalamus compared with non-drug-using controls. Within CD subjects, thalamic activation significantly correlated with treatment response. This study shows CD subjects in early abstinence have alterations of brain function in frontal, striatal, and thalamic brain regions known to be part of a circuit associated with motor control, reward, and cognition. Subjects with pretreatment thalamic deactivation showed the poorest treatment response, possibly related to thalamic involvement in mesocortical and mesolimbic dopamine projections.

Altered Effective Connectivity of Central Autonomic Network in Response to Negative Facial Expression in Adults With Cannabis Use Disorder.

BACKGROUND: Cannabis use is associated with an increased risk of stress-related adverse cardiovascular events. Because brain regions of the central autonomic network largely overlap with brain regions related to the neural response to emotion and stress, the central autonomic network may mediate the autonomic response to negative emotional stimuli. We aimed to obtain evidence to determine whether neural connectivity of the central autonomic network is altered in individuals with cannabis use disorder (CUD) when they are exposed to negative emotional stimuli. METHODS: Effective (directional) connectivity (EC) analysis using dynamic causal modeling was applied to functional magnetic resonance imaging data acquired from 23 subjects with CUD and 23 control subjects of the Human Connectome Project while they performed an emotional face-matching task with interleaving periods of negative-face (fearful/angry) and neutral-shape stimuli. The EC difference (modulatory change) was measured during the negative-face trials relative to the neutral-shape trials. RESULTS: The CUD group was similar to the control group in nonimaging measures and brain activations but showed greater modulatory changes in left amygdala to hypothalamus EC (positively associated with Perceived Stress Scale score), right amygdala to bilateral fusiform gyri ECs (positively associated with Perceived Stress Scale score), and left ventrolateral prefrontal cortex to bilateral fusiform gyri ECs (negatively associated with Perceived Stress Scale score). CONCLUSIONS: Left amygdala to hypothalamus EC and right amygdala to bilateral fusiform gyri ECs are possibly part of circuits underlying the risk of individuals with CUD to stress-related disorders. Correspondingly, left ventrolateral prefrontal cortex to bilateral fusiform gyri ECs are possibly part of circuits reflecting a protective mechanism.

Increased trait-like impulsivity and course of illness in bipolar disorder.

BACKGROUND: Impulsivity as a trait characteristic is increased in bipolar disorder and may be a core factor of the illness. We have investigated relationships between trait-like impulsivity, measured by the Barratt Impulsiveness Scale (BIS-11), and demographic and illness-course characteristics of bipolar disorder. METHODS: We studied 114 subjects with bipolar disorder and 71 healthy comparison subjects. Diagnoses were based on the Structured Clinical Interview for DSM-IV. In addition to impulsivity, we examined age, education, gender, psychiatric symptoms, and characteristics related to course of illness. We used general linear mixed model analysis to evaluate the manner in which the variables contributed to BIS-11 scores. RESULTS: All BIS-11 subscale scores were higher in bipolar disorder than in comparison subjects. There were less consistent independent effects of education and age. Elevated BIS-11 scores were associated with early onset, more frequent episodes of illness, and a history of suicide attempts. These relationships persisted when age, gender, and education were taken into account. DISCUSSION: These results show that, after accounting for common confounding factors, trait-like impulsivity was substantially higher in subjects with bipolar disorder than in nonbipolar comparison subjects, regardless of symptoms. Within subjects with bipolar disorder, high trait impulsivity was associated with a more severe course of illness.

A pilot study revealing impaired P50 gating in antisocial personality disorder.

The authors investigated preattentive filtering assessed by P50 gating in nine participants with antisocial personality disorder (ASPD) and seven with adult-onset antisocial behavior (AAB). Relative to 15 comparison subjects, gating was impaired in ASPD, suggesting abnormal pre-attentive filtering in pathological impulsivity.

Diminished P50, N100 and P200 auditory sensory gating in bipolar I disorder.

Bipolar I disorder is associated with diminished gating of the auditory evoked P50 component. P50 gating may relate to early filtering of sensory information, protecting higher-order cognitive functions. Gating of the auditory evoked N100 and P200 components has not been investigated in bipolar I disorder, although N100 and P200 gating could reflect different mechanisms and functions in the process of filtering sensory information in addition to those reflected by P50 gating. We investigated P50, N100, and P200 gating assessed with the paired-click paradigm in 22 subjects with bipolar I disorder and 54 healthy controls. Peak amplitudes and latencies were assessed at Cz for the P50, N100, and P200 components. Gating was defined as the reduction in peak amplitude from the first (S1) to the second stimulus (S2) of a stimulus pair, and expressed as gating ratio ([S2(amplitude)/S1(amplitude)]()100) and difference score (S1(amplitude)-S2(amplitude)). Group differences were detected with multivariate analyses and controlled for differences in age and ethnicity. Subjects with bipolar I disorder had higher P50, N100 and P200 ratios and lower difference scores compared with findings for controls. These findings extend the existing evidence on impaired sensory gating in bipolar I disorder beyond the P50, suggesting impaired filtering at both pre-attentive and early attentive levels in bipolar I disorder.