CBH Research

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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.
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.
The Time Course of Semantic and Relational Processing During Verbal Analogical Reasoning
(Academic Press Inc Elsevier Science, 2018-12-01) Kmiecik, Matthew J.; Brisson, Ryan J.; Morrison, Robert G.; Kmiecik, Matthew J.
Analogy is an important ability that allows humans to discover relationships between information domains that often vary in surface and relational characteristics. Cognitive neuroscience studies of analogy have demonstrated the importance of the prefrontal cortex during relational comparisons, but little is known about how semantic and relational similarity interact throughout its time course. We used scalp electroencephalography (EEG) analyzed with event-related potentials (ERPs) to examine the neural time course of analogical reasoning while 16 participants solved four-term verbal analogies. Semantic similarity was manipulated by increasing the semantic distance between source and target analogs creating semantically near and far analogies. Relational similarity was manipulated by creating relationally valid and invalid analogies. Only valid analogies were impacted by semantic distance such that far analogies were solved slower and less accurately than near analogies. Correctly solving near analogies elicited more positive waveforms at the N400 and during later relational processing. However, valid analogies elicited more positive signals during only later relational processing and not during the N400. These results suggest that semantic information impacts both early semantic and late relational comparison stages, while relational properties exert more influence in later stages of analogical reasoning. The degree of semantic similarity shared between knowledge domains demonstrated a potent effect throughout the time course of analogy that affected not only semantic access, but also the mapping of relational structures.
Relative Activation Patterns Associated with Self-Transcendent and Self-Enhancement Core Values: An fMRI Study of Basic Human Values Theory Concepts in Males
(Taylor and Francis Ltd., 2019-04-13) Teed, Adam R.; Rakic, Jelena; Mark, D. B.; Krawcyzk, Daniel C.; 0000-0003-3677-7164 (Teed, AR); Teed, Adam R.; Rakic, Jelena; Krawcyzk, Daniel C.
Core values have been shown to influence a variety of social behaviors, but research on the brain networks supporting their effects is sparse. While undergoing fMRI scanning, twenty male participants evaluated descriptions of real-world activities according to how worthwhile they were and how likely they were to participate in them. Each activity was categorized according to contexts conceptualized in the Basic Human Values Theory (BHVT) model of core values. We investigated two Self-enhancement values (Power and Achievement) and two Self-transcendent values (Benevolence and Universalism). Behavioral results indicated that Achievement and Benevolence activities were rated higher on both worthiness and participation willingness than Power and Universalism activities. Neuroimaging results revealed that self-transcendence activities elicited greater medial prefrontal cortex and anterior cingulate activation relative to self-enhancement activities during participation rated trials. Contrasting Power, Benevolence, and Universalism activities against Achievement activities during participation rated trials revealed a network of regions critical for moral processing, suggesting that activities corresponding to these three values were considered within a moral framework. No brain regions demonstrated activity that tracked behavioral ratings associated with specific values. This study expands upon previous core values research by demonstrating that real-world contexts related to different BHVT values elicit different brain regions. ©2019 Informa UK Limited, trading as Taylor & Francis Group.
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 Bond
Measuring 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.
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, Sven
Neuromodulation 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.
Three‐Dimensional Lesion Phenotyping and Physiologic Characterization Inform Remyelination Ability in Multiple Sclerosis
(American Society of Neuroimaging) Sivakolundu, Dinesh K.; Hansen, Madison R.; West, Kathryn L.; Wang, Yeqi; Stanley, Thomas; Wilson, Andrew; McCreary, Morgan; Turner, Monroe P.; Pinho, Marco C.; Newton, Braeden D.; Guo, Xiaohu; Rypma, Bart; Okuda, Darin T.; Sivakolundu, Dinesh K.; West, Kathryn L.; Wang, Yeqi; Stanley, Thomas; Wilson, Andrew; Turner, Monroe P.; Guo, Xiaohu; Rypma, Bart
BACKGROUND AND PURPOSE Multiple sclerosis (MS) clinical management is based upon lesion characterization from 2‐dimensional (2D) magnetic resonance imaging (MRI) views. Such views fail to convey the lesion‐phenotype (ie, shape and surface texture) complexity, underlying metabolic alterations, and remyelination potential. We utilized a 3‐dimensional (3D) lesion phenotyping approach coupled with imaging to study physiologic profiles within and around MS lesions and their impacts on lesion phenotypes. METHODS Lesions were identified in 3T T₂‐FLAIR images and segmented using geodesic active contouring. A calibrated fMRI sequence permitted measurement of cerebral blood flow (CBF), blood‐oxygen‐level‐dependent signal (BOLD), and cerebral metabolic rate of oxygen (CMRO₂). These metrics were measured within lesions and surrounding tissue in concentric layers exact to the 3D‐lesion shape. BOLD slope was calculated as BOLD changes from a lesion to its surrounding perimeters. White matter integrity was measured using diffusion kurtosis imaging. Associations between these metrics and 3D‐lesion phenotypes were studied. RESULTS One hundred nine lesions from 23 MS patients were analyzed. We identified a noninvasive biomarker, BOLD slope, to metabolically characterize lesions. Positive BOLD slope lesions were metabolically active with higher CMRO₂ and CBF compared to negative BOLD slope or inactive lesions. Metabolically active lesions with more intact white matter integrity had more symmetrical shapes and more complex surface textures compared to inactive lesions with less intact white matter integrity. CONCLUSION The association of lesion phenotypes with their metabolic signatures suggests the prospect for translation of such data to clinical management by providing information related to metabolic activity, lesion age, and risk for disease reactivation and self‐repair. Our findings also provide a platform for disease surveillance and outcome quantification involving myelin repair therapeutics.
A Multilevel Computational Characterization of Endophenotypes in Addiction
(Society for Neuroscience) Fiore, Vincenzo G.; Ognibene, D.; Adinoff, B.; Gu, Xiaosi; Fiore, Vincenzo G.; Gu, Xiaosi
Addiction 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.
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 Bond
Higher-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.
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, Leonidas
MicroRNAs 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.
Successful Classification of Cocaine Dependence Using Brain Imaging: A Generalizable Machine Learning Approach
(Biomed Central) Mete, Mutlu; Sakoglu, Unal; Spence, Jeffrey S.; Devous, Michael D.,Sr.; Harris, Thomas S.; Adinoff, Bryon; Spence, Jeffrey S.
BACKGROUND: Neuroimaging studies have yielded significant advances in the understanding of neural processes relevant to the development and persistence of addiction. However, these advances have not explored extensively for diagnostic accuracy in human subjects. The aim of this study was to develop a statistical approach, using a machine learning framework, to correctly classify brain images of cocaine-dependent participants and healthy controls. In this study, a framework suitable for educing potential brain regions that differed between the two groups was developed and implemented. Single Photon Emission Computerized Tomography (SPECT) images obtained during rest or a saline infusion in three cohorts of 2-4 week abstinent cocaine-dependent participants (n = 93) and healthy controls (n = 69) were used to develop a classification model. An information theoretic-based feature selection algorithm was first conducted to reduce the number of voxels. A density-based clustering algorithm was then used to form spatially connected voxel clouds in three-dimensional space. A statistical classifier, Support Vectors Machine (SVM), was then used for participant classification. Statistically insignificant voxels of spatially connected brain regions were removed iteratively and classification accuracy was reported through the iterations. RESULTS: The voxel-based analysis identified 1,500 spatially connected voxels in 30 distinct clusters after a grid search in SVM parameters. Participants were successfully classified with 0.88 and 0.89 F-measure accuracies in 10-fold cross validation (10xCV) and leave-one-out (LOO) approaches, respectively. Sensitivity and specificity were 0. 90 and 0.89 for LOO; 0.83 and 0.83 for 10xCV. Many of the 30 selected clusters are highly relevant to the addictive process, including regions relevant to cognitive control, default mode network related self-referential thought, behavioral inhibition, and contextual memories. Relative hyperactivity and hypoactivity of regional cerebral blood flow in brain regions in cocaine-dependent participants are presented with corresponding level of significance. CONCLUSIONS: The SVM-based approach successfully classified cocaine-dependent and healthy control participants using voxels selected with information theoretic-based and statistical methods from participants' SPECT data. The regions found in this study align with brain regions reported in the literature. These findings support the future use of brain imaging and SVM-based classifier in the diagnosis of substance use disorders and furthering an understanding of their underlying pathology.
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.
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.
When Physics Meets Biology: Low and High-Velocity Penetration, Blunt Impact, and Blast Injuries to the Brain
(Frontiers Research Foundation) Young, Leanne; Rule, Gregory T.; Bocchieri, Robert T.; Walilko, Timothy J.; Burns, Jennie M.; Ling, Geoffrey; Young, Leanne
The incidence of traumatic brain injuries (TBI) in the US has reached epidemic proportions with well over 2 million new cases reported each year. TBI can occur in both civilians and warfighters, with head injuries occurring in both combat and non-combat situations from a variety of threats, including ballistic penetration, acceleration, blunt impact, and blast. Most generally, TBI is a condition in which physical loads exceed the capacity of brain tissues to absorb without injury. More specifically, TBI results when sufficient external force is applied to the head and is subsequently converted into stresses that must be absorbed or redirected by protective equipment. If the stresses are not sufficiently absorbed or redirected, they will lead to damage of extracranial soft tissue and the skull. Complex interactions and kinematics of the head, neck and jaw cause strains within the brain tissue, resulting in structural, anatomical damage that is characteristic of the inciting insult. This mechanical trauma then initiates a neuro-chemical cascade that leads to the functional consequences of TBI, such as cognitive impairment. To fully understand the mechanisms by which TBI occurs, it is critically important to understand the effects of the loading environments created by these threats. In the following, a review is made of the pertinent complex loading conditions and how these loads cause injury. Also discussed are injury thresholds and gaps in knowledge, both of which are needed to design improved protective systems.;
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.
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.
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.
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 Bond
The 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.
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, Yan
Phase-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.
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, Bart
Breath 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.

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