Center for BrainHealth
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The Center for BrainHealth was created in 1999 and has flourished because of its unique commitment to its mission and the most significant cause of the century: To understand, protect and heal the brain. Scientific exploration at BrainHealth is leading edge, innovative and transformative, improving lives today and changing how the public thinks and acts about the brain and its health.
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Item A Multilevel Computational Characterization of Endophenotypes in Addiction(Society for Neuroscience) Fiore, Vincenzo G.; Ognibene, D.; Adinoff, B.; Gu, Xiaosi; Fiore, Vincenzo G.; Gu, XiaosiAddiction is characterized by a profound intersubject (phenotypic) variability in the expression of addictive symptomatology and propensity to relapse following treatment. However, laboratory investigations have primarily focused on common neural substrates in addiction and have not yet been able to identify mechanisms that can account for the multifaceted phenotypic behaviors reported in the literature. To fill this knowledge gap theoretically, here we simulated phenotypic variations in addiction symptomology and responses to putative treatments, using both a neural model, based on cortico-striatal circuit dynamics, and an algorithmic model of reinforcement learning (RL). These simulations rely on the widely accepted assumption that both the ventral, model-based, goal-directed system and the dorsal, model-free, habitual system are vulnerable to extra-physiologic dopamine reinforcements triggered by addictive rewards. We found that endophenotypic differences in the balance between the two circuit or control systems resulted in an inverted-U shape in optimal choice behavior. Specifically, greater unbalance led to a higher likelihood of developing addiction and more severe drug-taking behaviors. Furthermore, endophenotypes with opposite asymmetrical biases among cortico-striatal circuits expressed similar addiction behaviors, but responded differently to simulated treatments, suggesting personalized treatment development could rely on endophenotypic rather than phenotypic differentiations. We propose our simulated results, confirmed across neural and algorithmic levels of analysis, inform on a fundamental and, to date, neglected quantitative method to characterize clinical heterogeneity in addiction. © 2018 Fiore et al.Item Altered Amygdala Connectivity in Individuals with Chronic Traumatic Brain Injury and Comorbid Depressive Symptoms(Frontiers Media S.A.) Han, Kihwan; Chapman, Sandra Bond; Krawczyk, Daniel C.; 0000 0003 5170 3614 (Chapman, SB); 0000-0002-4574-7306 (Han, K); Han, Kihwan; Chapman, Sandra Bond; Krawczyk, Daniel C.Depression is one of the most common psychiatric conditions in individuals with chronic traumatic brain injury (TBI). Though depression has detrimental effects in TBI and network dysfunction is a "hallmark" of TBI and depression, there have not been any prior investigations of connectivity-based neuroimaging biomarkers for comorbid depression in TBI. We utilized resting-state functional magnetic resonance imaging to identify altered amygdala connectivity in individuals with chronic TBI (8 years post injury on average) exhibiting comorbid depressive symptoms (N = 31), relative to chronic TBI individuals having minimal depressive symptoms (N = 23). Connectivity analysis of these participant sub-groups revealed that the TBI-plus-depressive symptoms group showed relative increases in amygdala connectivity primarily in the regions that are part of the salience, somatomotor, dorsal attention, and visual networks P(voxel) < 0.01, P(cluster) < 0.025). Relative increases in amygdala connectivity in the TBI-plus-depressive symptoms group were also observed within areas of the limbic cortical mood regulating circuit (the left dorsomedial and right dorsolateral prefrontal cortices and thalamus) and the brainstem. Further analysis revealed that spatially dissociable patterns of correlation between amygdala connectivity and symptom severity according to subtypes (Cognitive and Affective) of depressive symptoms (p(voxel) < 0.01, p(duster) < 0.025). Taken together, these results suggest that amygdala connectivity may be a potentially effective neuroimaging biomarker for comorbid depressive symptoms in chronic TBI.Item Assessment of Unconstrained Cerebrovascular Reactivity Marker for Large Age-Range fMRI Studies(Public Library of Science) Kannurpatti, S. S.; Motes, Michael A.; Biswal, B. B.; Rypma, BartBreath hold (BH), a commonly used task to measure cerebrovascular reactivity (CVR) in fMRI studies varies in outcome among individuals due to subject-physiology and/or BH-inspiration/expiration differences (i.e., performance). In prior age-related fMRI studies, smaller task-related BOLD response variability is observed among younger than older individuals. Also, a linear CVR versus task relationship exists in younger individuals which maybe useful to test the accuracy of CVR responses in older groups. Hence we hypothesized that subject-related physiological and/or BH differences, if present, may compromise CVR versus task linearity in older individuals. To test the hypothesis, empirical BH versus task relationships from motor and cognitive areas were obtained in younger (mean age = 26 years) and older (mean age = 58 years) human subjects. BH versus task linearity was observed only in the younger group, confirming our hypothesis. Further analysis indicated BH responses and its variability to be similar in both younger and older groups, suggesting that BH may not accurately represent CVR in a large age range. Using the resting state fluctuation of amplitude (RSFA) as an unconstrained alternative to BH, subject-wise correspondence between BH and RSFA was tested. Correlation between BH versus RSFA was significant within the motor but was not significant in the cognitive areas in the younger and was completely disrupted in both areas in the older subjects indicating that BH responses are constrained by subject-related physiology and/or performance-related differences. Contrasting BH to task, RSFA-task relationships were independent of age accompanied by age-related increases in CVR variability as measured by RSFA, not observed with BH. Together the results obtained indicate that RSFA accurately represents CVR in any age range avoiding multiple and yet unknown physiologic and task-related pitfalls of BH.Item Automatic and Reproducible Positioning of Phase-Contrast MRI for the Quantification of Global Cerebral Blood Flow(Public Library of Science) Liu, Peiying; Lu, Hanzhang; Filbey, Francesca M.; Pinkham, Amy E.; McAdams, Carrie J.; Adinoff, Bryon; Daliparthi, Vamsi; Cao, Yan; 0000 0001 3618 6298 (Filbey, FM); 0000 0001 2904 8428 (Cao, Y); 11522796 (Cao, Y); Filbey, Francesca M.; Cao, YanPhase-Contrast MRI (PC-MRI) is a noninvasive technique to measure blood flow. In particular, global but highly quantitative cerebral blood flow (CBF) measurement using PC-MRI complements several other CBF mapping methods such as arterial spin labeling and dynamic susceptibility contrast MRI by providing a calibration factor. The ability to estimate blood supply in physiological units also lays a foundation for assessment of brain metabolic rate. However, a major obstacle before wider applications of this method is that the slice positioning of the scan, ideally placed perpendicular to the feeding arteries, requires considerable expertise and can present a burden to the operator. In the present work, we proposed that the majority of PC-MRI scans can be positioned using an automatic algorithm, leaving only a small fraction of arteries requiring manual positioning. We implemented and evaluated an algorithm for this purpose based on feature extraction of a survey angiogram, which is of minimal operator dependence. In a comparative test-retest study with 7 subjects, the blood flow measurement using this algorithm showed an inter-session coefficient of variation (CoV) of 4.07 ± 3.03%. The Bland-Altman method showed that the automatic method differs from the manual method by between -8% and 11%, for 95% of the CBF measurements. This is comparable to the variance in CBF measurement using manually-positioned PC MRI alone. In a further application of this algorithm to 157 consecutive subjects from typical clinical cohorts, the algorithm provided successful positioning in 89.7% of the arteries. In 79.6% of the subjects, all four arteries could be planned using the algorithm. Chi-square tests of independence showed that the success rate was not dependent on the age or gender, but the patients showed a trend of lower success rate (p = 0.14) compared to healthy controls. In conclusion, this automatic positioning algorithm could improve the application of PC-MRI in CBF quantification.Item Changing Pattern In The Basal Ganglia: Motor Switching Under Reduced Dopaminergic Drive(Nature Publications) Fiore, Vincenzo G.; Rigoli, Francesco; Stenner, Max-Philipp; Zaehle, Tino; Hirth, Frank; Heinze, Hans-Jochen; Dolan, Raymond J.; Fiore, Vincenzo G.Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson’s disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model.Item Cognitive Gains from Gist Reasoning Training in Adolescents with Chronic-Stage Traumatic Brain Injury(Frontiers Research Foundation) Cook, Lori G.; Chapman, Sandra Bond; Elliott, Alan C.; Evenson, Nellie N.; Vinton, Kami; 0000 0003 5170 3614 (Chapman, SB); 2012043141 (Chapman, SB)Adolescents with traumatic brain injury (TBI) typically demonstrate good recovery of previously acquired skills. However, higher-order and later emergent cognitive functions are often impaired and linked to poor outcomes in academic and social/behavioral domains. Few control trials exist that test cognitive treatment effectiveness at chronic recovery stages. The current pilot study compared the effects of two forms of cognitive training, gist reasoning (top-down) versus rote memory learning (bottom-up), on ability to abstract meanings, recall facts, and utilize core executive functions (i.e., working memory, inhibition) in 20 adolescents (ages 12-20) who were 6 months or longer post-TBI. Participants completed eight 45-min sessions over 1 month. After training, the gist reasoning group (n = 10) exhibited significant improvement in ability to abstract meanings and increased fact recall. This group also showed significant generalizations to untrained executive functions of working memory and inhibition. The memory training group (n = 10) failed to show significant gains in ability to abstract meaning or on other untrained specialized executive functions, although improved fact recall approached significance. These preliminary results suggest that relatively short-term training (6 h) utilizing a top-down reasoning approach is more effective than a bottom-up rote learning approach in achieving gains in higher-order cognitive abilities in adolescents at chronic stages of TBI. These findings need to be replicated in a larger study; nonetheless, the preliminary data suggest that traditional cognitive intervention schedules need to extend to later-stage training opportunities. Chronic-stage, higher-order cognitive trainings may serve to elevate levels of cognitive performance in adolescents with TBI. ;Item Enhancement of Cognitive and Neural Functions through Complex Reasoning Training: Evidence from Normal and Clinical Populations(Frontiers Research Foundation) Chapman, Sandra Bond; Mudar, Raksha A.; 0000 0003 5170 3614 (Chapman, SB); 2012043141 (Chapman, SB); Center for BrainHealthPublic awareness of cognitive health is fairly recent compared to physical health. Growing evidence suggests that cognitive training offers promise in augmenting cognitive brain performance in normal and clinical populations. Targeting higher-order cognitive functions, such as reasoning in particular, may promote generalized cognitive changes necessary for supporting the complexities of daily life. This data-driven perspective highlights cognitive and brain changes measured in randomized clinical trials that trained gist reasoning strategies in populations ranging from teenagers to healthy older adults, individuals with brain injury to those at-risk for Alzheimer's disease. The evidence presented across studies support the potential for Gist reasoning training to strengthen cognitive performance in trained and untrained domains and to engage more efficient communication across widespread neural networks that support higher-order cognition. The meaningful benefits of Gist training provide compelling motivation to examine optimal dose for sustained benefits as well as to explore additive benefits of meditation, physical exercise, and/or improved sleep in future studies. ;Item Enhancing Executive Function and Neural Health in Bipolar Disorder Through Reasoning Training(Frontiers Research Foundation) Venza, Erin E.; Chapman, Sandra Bond; Aslan, Sina; Zientz, Jennifer E.; Tyler, David L.; Spence, Jeffrey S.; 0000 0003 5170 3614 (Chapman, SB); Venza, Erin E.; Chapman, Sandra Bond; Aslan, Sina; Zientz, Jennifer E.; Tyler, David L.; Spence, Jeffrey S.Cognitive deficits in executive function and memory among individuals with bipolar disorder (BD) are well-documented; however, only recently have efforts begun to address whether such cognitive deficits can be ameliorated through cognitive training. This pilot study examined the effects of a top–down, cognitive reasoning training program in adults with BD on both brain and cognitive measures. Twenty-seven participants (11 males, 16 females), aged 21–70 years old, completed the study. Participants completed neurocognitive testing and functional magnetic resonance imaging (fMRI) before and after training, consisting of 8 h (2 h/week) of training in small groups. The training delivered information processing strategies that were implemented and applicable to a variety of daily living contexts. Results indicated that participants showed significant gains in the primary outcome measure of complex abstraction, also referred to as gist reasoning, as well as in untrained domains of executive function and memory. We found a significant increase in resting cerebral blood flow (CBF) in left inferior frontal gyrus after cognitive training. We also found that resting CBF in the right frontal middle gyrus correlated positively with performance on the measure of complex abstraction. This feasibility study provides promising evidence that short-term reasoning training can enhance cognitive performance and brain health in adults with BD. These data motivate further efforts to explore adjuvant therapeutics to improve cognitive performance and underlying brain systems in bipolar, as well as other psychiatric disorders.Item Enhancing Inferential Abilities in Adolescence: New Hope for Students in Poverty(Frontiers Research Foundation) Gamino, Jacquelyn F.; Motes, Michael M.; Riddle, Russell; Lyon, G. Reid; Spence, Jeffrey S.; Chapman, Sandra Bond; 0000 0003 5170 3614 (Chapman, SB); 2012043141 (Chapman, SB); Gamino, Jacquelyn F.; Motes, Michael M.; Riddle, Russell; Lyon, G. Reid; Spence, Jeffrey S.; Chapman, Sandra BondThe ability to extrapolate essential gist through the analysis and synthesis of information, prediction of potential outcomes, abstraction of ideas, and integration of relationships with world knowledge is critical for higher-order learning. The present study investigated the efficacy of cognitive training to elicit improvements in gist reasoning and fact recall ability in 556 public middle school students (grades seven and eight), vs. a sample of 357 middle school students who served as a comparison group, to determine if changes in gist reasoning and fact recall were demonstrated without cognitive training. The results showed that, in general, cognitive training increased gist reasoning and fact recall abilities in students from families in poverty as well as students from families living above poverty. However, the magnitude of gains in gist reasoning varied as a function of gender and grade level. Our primary findings were that seventh and eighth grade girls and eighth grade boys showed significant increases in gist reasoning after training regardless of socioeconomic status (SES). There were no significant increases in gist reasoning or fact recall ability for the 357 middle school students who served as a comparison group. We postulate that cognitive training in middle school is efficacious for improving gist reasoning ability and fact recall in students from all socioeconomic levels.Item Event-Related Neural Oscillation Changes Following Reasoning Training in Individuals with Mild Cognitive Impairment(Elsevier Science B.V., 2018-10-17) Mudar, Raksha A.; Nguyen, Lydia T.; Eroh, Justin; Chiang, Hsueh-Sheng; Rackley, Audette; Chapman, Sandra B.; Eroh, Justin; Rackley, Audette; Chapman, Sandra B.Emerging evidence suggests cognitive training programs targeting higher-order reasoning may strengthen not only cognitive, but also neural functions in individuals with Mild Cognitive Impairment (MCI). However, research on direct measures of training-induced neural changes, derivable from electroencephalography (EEG), is limited. The current pilot study examined effects of Gist Reasoning training (n = 16) compared to New Learning training (n = 16) in older adults with amnestic MCI on measures of event-related neural oscillations (theta and alpha band power) corresponding to Go/NoGo tasks during basic and superordinate semantic categorization. EEG data were recorded while participants performed the Go/NoGo task pre- and post-training, and power in theta and alpha frequency bands was examined. Both groups were comparable at pre-training on all measures and both groups showed greater event-related theta synchronization post-training. Furthermore, the Gist Reasoning group had enhanced event-related desynchronization in low-frequency alpha band (8-10 Hz)on response inhibition (NoGo) trials and high-frequency alpha band (11-13 Hz) on response execution (Go) trials during superordinate categorization, relative to the New Learning group. These findings suggest that Gist Reasoning training in MCI impacted neural processing linked to strategic processing of Go and NoGo trials during the more complex superordinate categorization task. Targeting higher-order top-down cognitive processing seems to better harness residual neuroplastic potential in MCI.Item Gulf War Illness Associated with Abnormal Auditory P1 Event-Related Potential: Evidence of Impaired Cholinergic Processing Replicated in a National Sample(Elsevier Ireland Ltd, 2018-11-10) Tillman, Gail D.; Spence, Jeffrey S.; Briggs, Richard W.; Haley, Robert W.; Hart, John; Kraut, Michael A.; Tillman, Gail D.; Hart, John, Jr.Our team previously reported event-related potential (ERP) and hyperarousal patterns from a study of one construction battalion of the U.S. Naval Reserve who served during the 1991 Persian Gulf War. We sought to replicate these findings in a sample that was more representative of the entire Gulf War-era veteran population, including male and female participants from four branches of the military. We collected ERP data from 40 veterans meeting Haley criteria for Gulf War syndromes 1-3 and from 22 matched Gulf War veteran controls while they performed an auditory oddball task. Reports of hyperarousal from the ill veterans were significantly greater than those from the control veterans, and P1 amplitudes in Syndromes 2 and 3 were significantly higher than P1 amplitudes in Syndrome 1, replicating our previous findings. Many of the contributors to the generation of the P1 potential are also involved in the regulation of arousal and are modulated by cholinergic and dopaminergic systems-two systems whose dysfunction has been implicated in Gulf War illness. These differences among the three syndrome groups where their means were on either side of controls is a replication of our previous ERP study and is consistent with previous imaging studies of this population.Item Higher-Order Cognitive Training Effects on Processing Speed-Related Neural Activity: A Randomized Trial(Elsevier) Yezhuvath, Uma S.; Aslan, Sina; Motes, Michael A.; Spence, Jeffrey S.; Rypma, Bart; Chapman, Sandra Bond; 0000 0003 5170 3614 (Chapman, SB); Motes, Michael A.; Aslan, Sina; Spence, Jeffrey S.; Rypma, Bart; Chapman, Sandra BondHigher-order cognitive training has shown to enhance performance in older adults, but the neural mechanisms underlying performance enhancement have yet to be fully disambiguated. This randomized trial examined changes in processing speed and processing speed-related neural activity in older participants (57-71years of age) who underwent cognitive training (CT, N= 12) compared with wait-listed (WLC, N= 15) or exercise-training active (AC, N= 14) controls. The cognitive training taught cognitive control functions of strategic attention, integrative reasoning, and innovation over 12weeks. All 3 groups worked through a functional magnetic resonance imaging processing speed task during 3 sessions (baseline, mid-training, and post-training). Although all groups showed faster reaction times (RTs) across sessions, the CT group showed a significant increase, and the WLC and AC groups showed significant decreases across sessions in the association between RT and BOLD signal change within the left prefrontal cortex (PFC). Thus, cognitive training led to a change in processing speed-related neural activity where faster processing speed was associated with reduced PFC activation, fitting previously identified neural efficiency profiles.Item Long-Term Effects of Marijuana Use on the Brain(Natl Acad Sciences) Filbey, Francesca M.; Aslan, Sina; Calhoun, Vince D.; Spence, Jeffrey S.; Damaraju, Eswar; Caprihan, Arvind; Segall, Judith; 0000 0001 3618 6298 (Filbey, FM); J-5163-2014 (Filbey, FM); Filbey, Francesca M.; Aslan, Sina; Spence, Jeffrey S.Questions surrounding the effects of chronic marijuana use on brain structure continue to increase. To date, however, findings remain inconclusive. In this comprehensive study that aimed to characterize brain alterations associated with chronic marijuana use, we measured gray matter (GM) volume via structural MRI across the whole brain by using voxel-based morphology, synchrony among abnormal GM regions during resting state via functional connectivity MRI, and white matter integrity (i.e., structural connectivity) between the abnormal GM regions via diffusion tensor imaging in 48 marijuana users and 62 age- and sex-matched nonusing controls. The results showed that compared with controls, marijuana users had significantly less bilateral orbitofrontal gyri volume, higher functional connectivity in the orbitofrontal cortex (OFC) network, and higher structural connectivity in tracts that innervate the OFC (forceps minor) as measured by fractional anisotropy (FA). Increased OFC functional connectivity in marijuana users was associated with earlier age of onset. Lastly, a quadratic trend was observed suggesting that the FA of the forceps minor tract initially increased following regular marijuana use but decreased with protracted regular use. This pattern may indicate differential effects of initial and chronic marijuana use that may reflect complex neuroadaptive processes in response to marijuana use. Despite the observed age of onset effects, longitudinal studies are needed to determine causality of these effects.Item Mapping the Operational Landscape of MicroRNAs in Synthetic Gene Circuits.(Nature Partner Journals, 2018-10-22) Quarton, Tyler; Ehrhardt, Kristina; Lee, James; Kannan, Srijaa; Li, Yi; Ma, Lan; Bleris, Leonidas; Quarton, Tyler; Ehrhardt, Kristina; Lee, James; Kannan, Srijaa; Li, Yi; Ma, Lan; Bleris, LeonidasMicroRNAs are a class of short, noncoding RNAs that are ubiquitous modulators of gene expression, with roles in development, homeostasis, and disease. Engineered microRNAs are now frequently used as regulatory modules in synthetic biology. Moreover, synthetic gene circuits equipped with engineered microRNA targets with perfect complementarity to endogenous microRNAs establish an interface with the endogenous milieu at the single-cell level. The function of engineered microRNAs and sensor systems is typically optimized through extensive trial-and-error. Here, using a combination of synthetic biology experimentation in human embryonic kidney cells and quantitative analysis, we investigate the relationship between input genetic template abundance, microRNA concentration, and output under microRNA control. We provide a framework that employs the complete operational landscape of a synthetic gene circuit and enables the stepwise development of mathematical models. We derive a phenomenological model that recapitulates experimentally observed nonlinearities and contains features that provide insight into the microRNA function at various abundances. Our work facilitates the characterization and engineering of multi-component genetic circuits and specifically points to new insights on the operation of microRNAs as mediators of endogenous information and regulators of gene expression in synthetic biology.Item The Network Architecture of Cortical Processing in Visuo-Spatial ReasoningShokri-Kojori, Ehsan; Motes, Michael A.; Rypma, Bart; Krawczyk, Daniel C.; School of Behavioral and Brain Sciences. Center for BrainHealth.Reasoning processes have been closely associated with prefrontal cortex (PFC), but specifically emerge from interactions among networks of brain regions. Yet it remains a challenge to integrate these brain-wide interactions in identifying the flow of processing emerging from sensory brain regions to abstract processing regions, particularly within PFC. Functional magnetic resonance imaging data were collected while participants performed a visuo-spatial reasoning task. We found increasing involvement of occipital and parietal regions together with caudal-rostral recruitment of PFC as stimulus dimensions increased. Brain-wide connectivity analysis revealed that interactions between primary visual and parietal regions predominantly influenced activity in frontal lobes. Caudal-to-rostral influences were found within left-PFC. Right-PFC showed evidence of rostral-to-caudal connectivity in addition to relatively independent influences from occipito-parietal cortices. In the context of hierarchical views of PFC organization, our results suggest that a caudal-to-rostral flow of processing may emerge within PFC in reasoning tasks with minimal top-down deductive requirements.Item Neural effects of positive and negative incentives during marijuana withdrawalFilbey, Francesca M.; Dunlop, Joseph; Myers, Ursula S.In spite of evidence suggesting two possible mechanisms related to drug-seeking behavior, namely reward-seeking and harm avoidance, much of the addiction literature has focused largely on positive incentivization mechanisms associated with addiction. In this study, we examined the contributing neural mechanisms of avoidance of an aversive state to drug-seeking behavior during marijuana withdrawal. To that end, marijuana users were scanned while performing the monetary incentive delay task in order to assess positive and negative incentive processes. The results showed a group x incentive interaction, such that marijuana users had greater response in areas that underlie reward processes during positive incentives while controls showed greater response in the same areas, but to negative incentives. Furthermore, a negative correlation between withdrawal symptoms and response in the amygdala during negative incentives was found in the marijuana users. These findings suggest that although marijuana users have greater reward sensitivity and less harm avoidance than controls, that attenuated amygdala response, an area that underlies fear and avoidance, was present in marijuana users with greater marijuana withdrawal symptoms. This is concordant with models of drug addiction that involve multiple sources of reinforcement in substance use disorders, and suggests the importance of strategies that focus on respective mechanisms.Item Neural Mechanisms of Behavioral Change in Young Adults with High-Functioning Autism Receiving Virtual Reality Social Cognition Training: A Pilot Study(Wiley) Yang, Y. J. Daniel; Allen, Tandra; Abdullahi, Sebiha M.; Pelphrey, Kevin A.; Volkmar, Fred R.; Chapman, Sandra Bond; Allen, Tandra; Chapman, Sandra BondMeasuring treatment efficacy in individuals with Autism Spectrum Disorder (ASD) relies primarily on behaviors, with limited evidence as to the neural mechanisms underlying these behavioral gains. This pilot study addresses this void by investigating neural and behavioral changes in a Phase I trial in young adults with high-functioning ASD who received an evidence-based behavioral intervention, Virtual Reality-Social Cognition Training over 5 weeks for a total of 10 hr. The participants were tested pre- and post-training with a validated biological/social versus scrambled/nonsocial motion neuroimaging task, previously shown to activate regions within the social brain networks. Three significant brain-behavior changes were identified. First, the right posterior superior temporal sulcus, a hub for socio-cognitive processing, showed increased brain activation to social versus nonsocial stimuli in individuals with greater gains on a theory-of-mind measure. Second, the left inferior frontal gyrus, a region for socio- emotional processing, tracked individual gains in emotion recognition with decreased activation to social versus nonsocial stimuli. Finally, the left superior parietal lobule, a region for visual attention, showed significantly decreased activation to nonsocial versus social stimuli across all participants, where heightened attention to nonsocial contingencies has been considered a disabling aspect of ASD. This study provides, albeit preliminary, some of the first evidence of the harnessable neuroplasticity in adults with ASD through an age-appropriate intervention in brain regions tightly linked to social abilities. This pilot trial motivates future efforts to develop and test social interventions to improve behaviors and supporting brain networks in adults with ASD. Autism Res2018, 11: 713-725. (c) 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. Lay SummaryThis study addresses how the behavioral changes after treatment for ASD reflect underlying brain changes. Before and after receiving VR-SCT, young adults with high-functioning ASD passively viewed biological motion stimuli in a MRI scanner, tapping changes in the social brain network. The results reveal neuroplasticity in this age population, extending the window of opportunity for interventions to impact social competency in adults with ASD.Item Optimization of Transcranial Direct Current Stimulation of Dorsolateral Prefrontal Cortex for Tinnitus: A Non-Linear Dose-Response Effect(Nature Publishing Group) Shekhawat, Giriraj Singh; Vanneste, Sven; Shekhawat, Giriraj Singh; 0000-0002-9906-1836 (Vanneste, S); Vanneste, SvenNeuromodulation is defined as the process of augmenting neuroplasticity via invasive or non-invasive methods. Tinnitus is the perception of sound in the absence of its external source. The objective of this study was to optimize the parameters of transcranial direct current stimulation (tDCS) of dorsolateral prefrontal cortex (DLPFC) for tinnitus suppression. The following factors were optimized in the dose-response design (n = 111): current intensity (1.5 mA or 2 mA), stimulation duration (20 min or 30 min), and number of stimulation sessions (2, 4, 6, 8, or 10), with a 3-4 day washout period between each session. Participants underwent a minimum of 2 sessions in 1 week or maximum of 10 sessions in 5 weeks' time. Tinnitus loudness was measured in pre-post design using a 10-point numeric rating scale. There was a significant reduction in tinnitus loudness after tDCS of DLPFC. There was no significant difference between the intensity and duration of stimulation. As the number of sessions increased, there was a higher reduction in the tinnitus loudness; however, this effect plateaued after 6 sessions.Item Preliminary Findings Demonstrating Latent Effects of Early Adolescent Marijuana Use Onset on Cortical Architecture(Elsevier Sci Ltd) Filbey, Francesca M.; McQueeny, Tim; DeWitt, Samuel J.; Mishra, Virendra; 0000 0001 3618 6298 (Filbey, FM); Filbey, Francesca M.; McQueeny, Tim; DeWitt, Samuel J.Background: As the most commonly used illicit substance during early adolescence, long-term or latent effects of early adolescent marijuana use across adolescent developmental processes remain to be determined. Methods: We examined cortical thickness, gray/white matter border contrast (GWR) and local gyrification index (LGI) in 42 marijuana (MJ) users. Voxelwise regressions assessed early-onset (age = 16 years-old) differences and relationships to continued use while controlling for current age and alcohol use. Results: Although groups did not differ by onset status, groups diverged in their correlations between cannabis use and cortical architecture. Among early-onset users, continued years of MJ use and current MJ consumption were associated with thicker cortex, increased GWR and decreased LGI. Late-onset users exhibited the opposite pattern. This divergence was observed in all three morphological measures in the anterior dorsolateral frontal cortex (p < .05, FWE-corrected). Conclusions: Divergent patterns between current MJ use and elements of cortical architecture were associated with early MJ use onset. Considering brain development in early adolescence, findings are consistent with disruptions in pruning. However, divergence with continued use for many years thereafter suggests altered trajectories of brain maturation during late adolescence and beyond.Item Recommendations for the Use of Common Outcome Measures in Pediatric Traumatic Brain Injury ResearchMcCauley, Stephen R.; Wilde, Elisabeth A.; Anderson, Vicki A.; Bedell, Gary; Beers, Sue R.; Campbell, Thomas F.; Chapman, Sandra Bond; 0000 0003 5170 3614 (Chapman, SB); 2012043141 (Chapman, SB); Callier Center for Communication Disorders; Center for BrainHealthThis article addresses the need for age-relevant outcome measures for traumatic brain injury (TBI) research and summarizes the recommendations by the inter-agency Pediatric TBI Outcomes Workgroup. The Pediatric Workgroup's recommendations address primary clinical research objectives including characterizing course of recovery from TBI, prediction of later outcome, measurement of treatment effects, and comparison of outcomes across studies. Consistent with other Common Data Elements (CDE) Workgroups, the Pediatric TBI Outcomes Workgroup adopted the standard three-tier system in its selection of measures. In the first tier, core measures included valid, robust, and widely applicable outcome measures with proven utility in pediatric TBI from each identified domain including academics, adaptive and daily living skills, family and environment, global outcome, health-related quality of life, infant and toddler measures, language and communication, neuropsychological impairment, physical functioning, psychiatric and psychological functioning, recovery of consciousness, social role participation and social competence, social cognition, and TBI-related symptoms. In the second tier, supplemental measures were recommended for consideration in TBI research focusing on specific topics or populations. In the third tier, emerging measures included important instruments currently under development, in the process of validation, or nearing the point of published findings that have significant potential to be superior to measures in the core and supplemental lists and may eventually replace them as evidence for their utility emerges.