Neural processes of inhibitory control in American Indian peoples are associated with reduced mental health problems.

American Indians (AI) experience disproportionately high prevalence of suicide and substance use disorders (SUD). However, accounting for risk burden (e.g. historical trauma and discrimination), the likelihood of mental health disorders or SUD is similar or decreased compared with the broader population. Such findings have spurred psychological research examining the protective factors, but no studies have investigated its potential neural mechanisms. Inhibitory control is one of the potential neurobehavioral construct with demonstrated protective effects, but has not been examined in neuroimaging studies with AI populations specifically. We examined the incidence of suicidal thoughts and behaviors (STB) and SUD among AI (n = 76) and propensity matched (sex, age, income, IQ proxy and trauma exposure) non-Hispanic White (NHW) participants (n = 76). Among the AI sample, functional magnetic resonance imaging (fMRI) data recorded during the stop-signal task (SST) was examined in relation to STB and SUDs. AIs relative to NHW subjects displayed lower incidence of STB. AIs with no reported STBs showed greater activity in executive control regions during the SST compared with AI who endorsed STB. AI without SUD demonstrated lower activity relative to those individual reporting SUD. Results are consistent with a growing body of literature demonstrating the high level of risk burden driving disparate prevalence of mental health concerns in AI. Furthermore, differential activation during inhibitory control processing in AI individuals without STB may represent a neural mechanism of protective effects against mental health problems in AI. Future research is needed to elucidate sociocultural factors contributing protection against mental health outcomes in AIs and further delineate neural mechanisms with respect to specific concerns (e.g. SUD vs STB).

A machine learning analysis of risk and protective factors of suicidal thoughts and behaviors in college students.

OBJECTIVE: To identify robust and reproducible factors associated with suicidal thoughts and behaviors (STBs) in college students. METHODS: 356 first-year university students completed a large battery of demographic and clinically-relevant self-report measures during the first semester of college and end-of-year (n = 228). Suicide Behaviors Questionnaire-Revised (SBQ-R) assessed STBs. A machine learning (ML) pipeline using stacking and nested cross-validation examined correlates of SBQ-R scores. RESULTS: 9.6% of students were identified at significant STBs risk by the SBQ-R. The ML algorithm explained 28.3% of variance (95%CI: 28-28.5%) in baseline SBQ-R scores, with depression severity, social isolation, meaning and purpose in life, and positive affect among the most important factors. There was a significant reduction in STBs at end-of-year with only 1.8% of students identified at significant risk. CONCLUSION: Analyses replicated known factors associated with STBs during the first semester of college and identified novel, potentially modifiable factors including positive affect and social connectedness.

A randomized clinical trial of behavioral activation and exposure-based therapy for adults with generalized anxiety disorder.

Objective: Exposure-based therapy (EXP) and behavioral activation (BA) are empirically-supported behavioral intervention techniques that target avoidance and approach behavior to alleviate symptoms. Although EXP is an established treatment for generalized anxiety disorder (GAD), the effectiveness of BA for GAD has not been directly tested or compared with that of EXP. This study examined the efficacy of EXP and BA for adults with GAD. Method: In a randomized clinical trial (clinicaltrials.gov: NCT02807480) with partial blinding in Tulsa, OK, 102 adults with GAD were allocated to manualized, 10-session EXP or BA between April 2016-April 2021. Primary analyses were intention-to-treat and included the 94 (46 EXP, 48 BA) participants who started treatment. The GAD-7 self-report scale was the primary outcome measure. Results: Similar GAD-7 declines were observed at post-treatment for EXP (d=-0.97 [95% CI -1.40 to -0.53]) and BA (d=-1.14 [95% CI -1.57 to -0.70]), and were maintained through 6-month follow-up (EXP: d=-2.13, BA: d=-1.98). Compared to EXP, BA yielded more rapid declines in anxiety and depression scores during therapy (d=0.75-0.77), as well as lower anxiety and depression scores (d=0.13-0.14) and greater participant-rated improvement (d=0.64) at post-treatment. Bayesian analyses indicated 74-99% probability of greater change in BA than EXP at post-treatment. Conclusions: BA and EXP are both effective in treating GAD, and BA may confer greater benefit during treatment. Future research is warranted to inform personalized treatment approaches.

Striatal reactivity during emotion and reward relates to approach-avoidance conflict behaviour and is altered in adults with anxiety or depression.

BACKGROUND: We have previously reported activation in reward, salience and executive control regions during functional MRI (fMRI) using an approach-avoidance conflict (AAC) decision-making task with healthy adults. Further investigations into how anxiety and depressive disorders relate to differences in neural responses during AAC can inform their understanding and treatment. We tested the hypothesis that people with anxiety or depression have altered neural activation during AAC. METHODS: We compared 118 treatment-seeking adults with anxiety or depression and 58 healthy adults using linear mixed-effects models to examine group-level differences in neural activation (fMRI) during AAC decision-making. Correlational analyses examined relationships between behavioural and neural measures. RESULTS: Adults with anxiety or depression had greater striatal engagement when reacting to affective stimuli (p = 0.008, d = 0.31) regardless of valence, and weaker striatal engagement during reward feedback (p = 0.046, d = -0.27) regardless of the presence of monetary reward. They also had blunted amygdala activity during decision-making (p = 0.023, d = -0.32) regardless of the presence of conflict. Across groups, approach behaviour during conflict decision-making was inversely correlated with striatal activation during affective stimuli (p < 0.001, r = -0.28) and positively related to striatal activation during reward feedback (p < 0.001, r = 0.27). LIMITATIONS: Our transdiagnostic approach did not allow for comparisons between specific anxiety disorders, and our cross-sectional approach did not allow for causal inference. CONCLUSION: Anxiety and depression were associated with altered neural responses to AAC. Findings were consistent with the role of the striatum in action selection and reward responsivity, and they point toward striatal reactivity as a future treatment target. Blunting of amygdala activity in anxiety or depression may indicate a compensatory response to inhibit affective salience and maintain approach.

Active coping strategies and less pre-pandemic alcohol use relate to college student mental health during the COVID-19 pandemic.

Objective: To further delineate risk and resilience factors contributing to trajectories of mental health symptoms experienced by college students through the pandemic. Participants: n = 183 college students (67.2% female). Methods: Linear mixed models examined time effects on depression and anxiety. Propensity-matched subgroups exhibiting "increased" versus "low and stable" depression symptoms from before to after the pandemic-onset were compared on pre-pandemic demographic and psychological factors and COVID-related experiences and coping strategies. Results: Students experienced worsening of mental health symptoms throughout the pandemic, particularly during Fall 2020 compared with Fall 2019 (Depression scale d = -0.43 [95% CI: -0.65 to -0.21]). The propensity-matched subgroup exhibiting relative resilience ("low and stable" symptoms) reported less alcohol use prior to the pandemic, greater use of active coping strategies, and less of an impact on their college progress. Conclusions: Results point to several potential targets of screening and intervention to decrease residual impacts of the pandemic.

Limits to the generalizability of resting-state functional magnetic resonance imaging studies of youth: An examination of ABCD Study® baseline data.

This study examined how resting-state functional magnetic resonance imaging (rs-fMRI) data quality and availability relate to clinical and sociodemographic variables within the Adolescent Brain Cognitive Development Study. A sample of participants with an adequate sample of quality baseline rs-fMRI data containing low average motion (framewise displacement ≤ 0.15; low-noise; n = 4,356) was compared to a sample of participants without an adequate sample of quality data and/or containing high average motion (higher-noise; n = 7,437) using Chi-squared analyses and t-tests. A linear mixed model examined relationships between clinical and sociodemographic characteristics and average head motion in the sample with low-noise data. Relative to the sample with higher-noise data, the low-noise sample included more females, youth identified by parents as non-Hispanic white, and youth with married parents, higher parent education, and greater household incomes (ORs = 1.32-1.42). Youth in the low-noise sample were also older and had higher neurocognitive skills, lower BMIs, and fewer externalizing and neurodevelopmental problems (ds = 0.12-0.30). Within the low-noise sample, several clinical and demographic characteristics related to motion. Thus, participants with low-noise rs-fMRI data may be less representative of the general population and motion may remain a confound in this sample. Future rs-fMRI studies of youth should consider these limitations in the design and analysis stages in order to optimize the representativeness and clinical relevance of analyses and results.

Self-regulation of the posterior cingulate cortex with real-time fMRI neurofeedback augmented mindfulness training in healthy adolescents: A nonrandomized feasibility study.

Mindfulness training (MT) promotes the development of one's ability to observe and attend to internal and external experiences with objectivity and nonjudgment with evidence to improve psychological well-being. Real-time functional MRI neurofeedback (rtfMRI-nf) is a noninvasive method of modulating activity of a brain region or circuit. The posterior cingulate cortex (PCC) has been hypothesized to be an important hub instantiating a mindful state. This nonrandomized, single-arm study examined the feasibility and tolerability of training typically developing adolescents to self-regulate the posterior cingulate cortex (PCC) using rtfMRI-nf during MT. Thirty-four adolescents (mean age: 15 years; 14 females) completed the neurofeedback augmented mindfulness training task, including Focus-on-Breath (MT), Describe (self-referential thinking), and Rest conditions, across three neurofeedback and two non-neurofeedback runs (Observe, Transfer). Self-report assessments demonstrated the feasibility and tolerability of the task. Neurofeedback runs differed significantly from non-neurofeedback runs for the Focus-on-Breath versus Describe contrast, characterized by decreased activity in the PCC during the Focus-on-Breath condition (z = -2.38 to -6.27). MT neurofeedback neural representation further involved the medial prefrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex, posterior insula, hippocampus, and amygdala. State awareness of physical sensations increased following rtfMRI-nf and was maintained at 1-week follow-up (Cohens' d = 0.69). Findings demonstrate feasibility and tolerability of rtfMRI-nf in healthy adolescents, replicates the role of PCC in MT, and demonstrate a potential neuromodulatory mechanism to leverage and streamline the learning of mindfulness practice. ( ClinicalTrials.gov identifier #NCT04053582; August 12, 2019).

Amplification of Positivity Therapy for Co-occurring Alcohol Use Disorder with Depression and Anxiety Symptoms: Pilot Feasibility Study and Case Series.

Positive valence system dysregulation is a relatively unexplored transdiagnostic mechanism and potential treatment target underpinning alcohol use and anxiety and depression symptoms. The current study examined the feasibility and potential benefit of a behavioral intervention focused on amplification of positivity (AMP) with eight adults (five female) diagnosed with alcohol use disorder and clinically significant depression or anxiety (ClinicalTrials.gov: NCT04278365). AMP for alcohol use (AMP-A) was delivered in 11 individual sessions involving positive activity interventions integrated alongside psychoeducation and alcohol use monitoring. Case descriptions are provided to illustrate treatment implementation. Treatment credibility and acceptability, participant endorsement of the therapy, and homework compliance were rated moderate to high. Exploratory, intent-to-treat analyses suggested medium to large effect sizes for post-treatment improvements in alcohol use, depression, anxiety, and positive affect. Results provide initial evidence of feasibility and acceptability of AMP-A and will be useful for informing future randomized clinical trials to examine clinical efficacy.

P300 amplitude during a monetary incentive delay task predicts future therapy completion in individuals with major depressive disorder.

INTRODUCTION: Treatment effectiveness for major depressive disorder (MDD) is often affected by client non-adherence, dropout, and non-response. Identification of client characteristics predicting successful treatment completion and/or response (i.e., symptom reduction) may be an important tool to increase intervention effectiveness. It is unclear whether neural attenuations in reward processing associated with MDD predict behavioral treatment outcome. METHODS: This study aimed to determine whether blunted neural responses to reward at baseline differentiate MDD (n = 60; 41 with comorbid anxiety) and healthy control (HC; n = 40) groups; and predict MDD completion of and response to 7-10 sessions of behavior therapy. Participants completed a monetary incentive delay (MID) task. The N200, P300, contingent negative variation (CNV) event related potentials (ERPs) and behavioral responses (reaction time [RT], correct hits) were quantified and extracted for cross-sectional group analyses. ERPs and behavioral responses demonstrating group differences were then used to predict therapy completion and response within MDD. RESULTS: MDD exhibited faster RT and smaller P300 amplitudes than HC across conditions. Within the MDD group, treatment completers (n = 37) exhibited larger P300 amplitudes than non-completers (n = 21). LIMITATIONS: This study comprises secondary analyses of EEG data; thus task parameters are not optimized to examine feedback ERPs from the paradigm. We did not examine heterogenous presentations of MDD; however, severity and comorbidity did not influence findings. CONCLUSIONS: Previous studies suggest that P300 is an index of motivational salience and stimulus resource allocation. In sum, individuals who deploy greater neural resources to task demands are more likely to persevere in behavioral therapy.

Long-term stability of computational parameters during approach-avoidance conflict in a transdiagnostic psychiatric patient sample.

Maladaptive behavior during approach-avoidance conflict (AAC) is common to multiple psychiatric disorders. Using computational modeling, we previously reported that individuals with depression, anxiety, and substance use disorders (DEP/ANX; SUDs) exhibited differences in decision uncertainty and sensitivity to negative outcomes versus reward (emotional conflict) relative to healthy controls (HCs). However, it remains unknown whether these computational parameters and group differences are stable over time. We analyzed 1-year follow-up data from a subset of the same participants (N = 325) to assess parameter stability and relationships to other clinical and task measures. We assessed group differences in the entire sample as well as a subset matched for age and IQ across HCs (N = 48), SUDs (N = 29), and DEP/ANX (N = 121). We also assessed 2-3 week reliability in a separate sample of 30 HCs. Emotional conflict and decision uncertainty parameters showed moderate 1-year intra-class correlations (.52 and .46, respectively) and moderate to excellent correlations over the shorter period (.84 and .54, respectively). Similar to previous baseline findings, parameters correlated with multiple response time measures (ps < .001) and self-reported anxiety (r = .30, p < .001) and decision difficulty (r = .44, p < .001). Linear mixed effects analyses revealed that patients remained higher in decision uncertainty (SUDs, p = .009) and lower in emotional conflict (SUDs, p = .004, DEP/ANX, p = .02) relative to HCs. This computational modelling approach may therefore offer relatively stable markers of transdiagnostic psychopathology.

Test-retest reliability of approach-avoidance conflict decision-making during functional magnetic resonance imaging in healthy adults.

Neural and behavioral mechanisms during approach-avoidance conflict decision-making are relevant across various psychiatric disorders, particularly anxiety disorders. Studies using approach-avoidance conflict paradigms in healthy adults have identified preliminary neural mechanisms, but findings must be replicated and demonstrated as reliable before further application. This study sought to replicate previous findings and examine test-retest reliability of behavioral (approach behavior, reaction time) and neural (regions of interest [ROIs]) responses during an approach-avoidance conflict task conducted during functional magnetic resonance imaging (fMRI). Thirty healthy adults completed an approach-avoidance conflict task during fMRI on two occasions (mean interval: 17 days; range: 11-32). Effects of task condition during three task phases (decision-making, affective outcome and monetary reward) and intraclass correlation coefficients (ICCs) were calculated across time points. Results replicated that approach behavior was modulated by conflict during decision-making. ROI activations were replicated such that dorsal anterior cingulate cortex (dACC) was modulated by conflict during decision-making, and dACC, striatum, and anterior insula were modulated by valence during affective outcomes (p's <.0083). Approach behavior during conflict demonstrated excellent reliability (ICCs ≥.77). Activation of dACC during conflict decision-making and anterior insula during negative outcomes demonstrated fair reliability (ICCs = .51 and .54), and dACC and striatum activation demonstrated good reliability during negative outcomes (ICCs = .63 and .69). Two additional ROIs (amygdala, left dorsolateral prefrontal cortex) showed good reliability during negative outcomes (ICCs ≥.60). These results characterize several specific behavioral and neuroimaging responses that are replicable and sufficiently reliable during approach-avoidance conflict decision-making to support future utility.

Visual cortical regions show sufficient test-retest reliability while salience regions are unreliable during emotional face processing.

Functional magnetic resonance imaging studies frequently use emotional face processing tasks to probe neural circuitry related to psychiatric disorders and treatments with an emphasis on regions within the salience network (e.g., amygdala). Findings across previous test-retest reliability studies of emotional face processing have shown high variability, potentially due to differences in data analytic approaches. The present study comprehensively examined the test-retest reliability of an emotional faces task utilizing multiple approaches to region of interest (ROI) analysis and by examining voxel-wise reliability across the entire brain for both neural activation and functional connectivity. Analyses included 42 healthy adult participants who completed an fMRI scan concurrent with an emotional faces task on two separate days with an average of 25.52 days between scans. Intraclass correlation coefficients (ICCs) were calculated for the 'FACES-SHAPES' and 'FACES' (compared to implicit baseline) contrasts across the following: anatomical ROIs identified from a publicly available brain atlas (i.e., Brainnetome), functional ROIs consisting of 5-mm spheres centered on peak voxels from a publicly available meta-analytic database (i.e., Neurosynth), and whole-brain, voxel-wise analysis. Whole-brain, voxel-wise analyses of functional connectivity were also conducted using both anatomical and functional seed ROIs. While group-averaged neural activation maps were consistent across time, only one anatomical ROI and two functional ROIs showed good or excellent individual-level reliability for neural activation. The anatomical ROI was the right medioventral fusiform gyrus for the FACES contrast (ICC â€‹= â€‹0.60). The functional ROIs were the left and the right fusiform face area (FFA) for both FACES-SHAPES and FACES (Left FFA ICCs â€‹= â€‹0.69 & 0.79; Right FFA ICCs â€‹= â€‹0.68 & 0.66). Poor reliability (ICCs â€‹< â€‹0.4) was identified for almost all other anatomical and functional ROIs, with some exceptions showing fair reliability (ICCs â€‹= â€‹0.4-0.59). Whole-brain voxel-wise analysis of neural activation identified voxels with good (ICCs â€‹= â€‹0.6-0.74) to excellent reliability (ICCs â€‹> â€‹0.75) that were primarily located in visual cortex, with several clusters in bilateral dorsal lateral prefrontal cortex (DLPFC). Whole-brain voxel-wise analyses of functional connectivity for amygdala and fusiform gyrus identified very few voxels with good to excellent reliability using both anatomical and functional seed ROIs. Exceptions included clusters in right cerebellum and right DLPFC that showed reliable connectivity with left amygdala (ICCs â€‹> â€‹0.6). In conclusion, results indicate that visual cortical regions demonstrate good reliability at the individual level for neural activation, but reliability is generally poor for salience regions often focused on within psychiatric research (e.g., amygdala). Given these findings, future clinical neuroimaging studies using emotional faces tasks to examine individual differences might instead focus on visual regions and their role in psychiatric disorders.

A pragmatic clinical trial examining the impact of a resilience program on college student mental health.

BACKGROUND: One in three college students experience significant depression or anxiety interfering with daily functioning. Resilience programs that can be administered to all students offer an opportunity for addressing this public health problem. The current study objective was to assess the benefit of a brief, universal resilience program for first-year college students. METHOD: First-year students at a private, midwestern university participated. This trial used a pragmatic design, delivering the intervention within university-identified orientation courses and was not randomized. The four-session resilience program included goal-building, mindfulness, and resilience skills. The comparison was orientation-as-usual. Primary outcomes included PROMIS® Depression and Anxiety and Connor-Davidson Resilience Scale. Secondary and exploratory outcomes included the Perceived Stress Scale, Emotion Regulation, and Cognitive Behavioral Therapy (CBT) Skills Questionnaires, and Freiburg Mindfulness Inventory. Time by treatment interactions at post-training and semester-end were examined using linear mixed models. RESULTS: Analysis included 252 students, 126 who completed resilience programming and a matched comparison sample. Resilience programming did not relate to improvements in depression at post-training (CI: -2.53 to 1.02; p = .404, d =-0.08), but did at semester-end (95% CI: -4.27 to -0.72; p = .006, d = -0.25) and improvements in perceived stress were observed at post-training (CI: -3.31 to -0.44; p = .011, d = -0.24) and semester-end (CI: -3.30 to -0.41; p = .013, d = -0.24). Emotion regulation, mindfulness, and CBT skills increased, with CBT skills mediating clinical improvements. CONCLUSIONS: Universal implementation of a brief, resilience intervention may be effective for improving college student mental health.

The developmental trajectory of sensorimotor cortical oscillations.

Numerous studies of motor control have confirmed beta and gamma oscillations in the primary motor cortices during basic movements. These responses include a robust beta decrease that precedes and extends through movement onset, a transient gamma response that coincides with the movement, and a post-movement beta rebound (PMBR) response that occurs after movement offset. While the existence of these responses has been confirmed by many studies, very few studies have examined their developmental trajectory. In the current study, we utilized magnetoencephalography (MEG) to investigate age-related changes in sensorimotor cortical oscillations in a large cross-section of children and adolescents (n = 94; age range = 9 -15 years-old). All participants performed a stimulus detection task with their right finger and the resulting MEG data were examined using oscillatory analysis methods and imaged using a beamformer. Consistent with adult studies, these youth participants exhibited characteristic beta (16-24 Hz) decreases prior to and during movement, as well as PMBR responses following movement offset, and a transient gamma (74-84 Hz) response during movement execution. Our primary findings were that the strength of the PMBR increased with age, while the strength of the gamma synchronization decreased with chronological age. In addition, the strength of each motor-related oscillatory response was significantly correlated with the power of spontaneous activity in the same frequency range and same voxel. This was the case for all three oscillatory responses. In conclusion, we investigated motor-related oscillatory activity in the largest cohort of children and adolescents reported to date, and our results indicated that beta and gamma cortical oscillations continue to develop as children transition into adolescents, and that these responses may not be fully matured until young to middle adulthood.

The impact of type 1 diabetes on neural activity serving attention.

Type 1 diabetes has been associated with alterations in attentional processing and other cognitive functions, and previous studies have found alterations in both brain structure and function in affected patients. However, these previous neuroimaging studies have generally examined older patients, particularly those with major comorbidities known to affect functioning independent of diabetes. The primary aim of the current study was to examine the neural dynamics of selective attention processing in a young group of patients with type 1 diabetes who were otherwise healthy (i.e., without major comorbidities). Our hypothesis was that these patients would exhibit significant aberrations in attention circuitry relative to closely matched controls. The final sample included 69 participants age 19-35 years old, 35 with type 1 diabetes and 34 matched nondiabetic controls, who completed an Eriksen flanker task while undergoing magnetoencephalography. Significant group differences in flanker interference activity were found across a network of brain regions, including the anterior cingulate, inferior parietal cortices, paracentral lobule, and the left precentral gyrus. In addition, neural activity in the anterior cingulate and the paracentral lobule was correlated with disease duration in patients with type 1 diabetes. These findings suggest that alterations in the neural circuitry underlying selective attention emerge early in the disease process and are specifically related to type 1 diabetes and not common comorbidities. These findings highlight the need for longitudinal studies in large cohorts to clarify the clinical implications of type 1 diabetes on cognition and the brain.

tDCS modulates behavioral performance and the neural oscillatory dynamics serving visual selective attention.

Transcranial direct-current stimulation (tDCS) is a noninvasive method for modulating human brain activity. Although there are several hypotheses about the net effects of tDCS on brain function, the field's understanding remains incomplete and this is especially true for neural oscillatory activity during cognitive task performance. In this study, we examined whether different polarities of occipital tDCS differentially alter flanker task performance and the underlying neural dynamics. To this end, 48 healthy adults underwent 20 min of anodal, cathodal, or sham occipital tDCS, and then completed a visual flanker task during high-density magnetoencephalography (MEG). The resulting oscillatory responses were imaged in the time-frequency domain using beamforming, and the effects of tDCS on task-related oscillations and spontaneous neural activity were assessed. The results indicated that anodal tDCS of the occipital cortices inhibited flanker task performance as measured by reaction time, elevated spontaneous activity in the theta (4-7 Hz) and alpha (9-14 Hz) bands in prefrontal and occipital cortices, respectively, and reduced task-related theta oscillatory activity in prefrontal cortices during task performance. Cathodal tDCS of the occipital cortices did not significantly affect behavior or any of these neuronal parameters in any brain region. Lastly, the power of theta oscillations in the prefrontal cortices was inversely correlated with reaction time. In conclusion, anodal tDCS modulated task-related oscillations and spontaneous activity across multiple cortical areas, both near the electrode and in distant sites that were putatively connected to the targeted regions.

Neural dynamics of selective attention deficits in HIV-associated neurocognitive disorder.

OBJECTIVE: To identify the neural markers of attention dysfunction in patients with HIV-associated neurocognitive disorder (HAND). METHODS: Sixty participants, including 40 HIV-infected adults (half with HAND) and 20 demographically matched controls performed a visual selective attention task while undergoing high-density magnetoencephalography. Neuronal activity related to selective attention processing was quantified and compared across the 3 groups, and correlated with neuropsychological measures of attention and executive function. Spontaneous neural activity was also extracted from these attention-related cortical areas and examined with respect to HAND status. RESULTS: HIV-infected participants with and without HAND exhibited behavioral selective attention deficits on the magnetoencephalography task, as indicated by an increased flanker effect. Neuronal measures of flanker interference activity in the alpha and theta range revealed differential dynamics in attention-related brain areas across the 3 groups, especially in those with HAND. In addition, theta range flanker interference activity in the left inferior frontal and dorsolateral prefrontal cortex was associated with executive function and attention composite scores, respectively. Progressively stronger spontaneous alpha and theta activity was also found in unimpaired HIV-infected and HAND participants relative to controls across brain regions implicated in different components of attention processing. CONCLUSIONS: Behavioral and neuronal metrics of selective attention performance distinguish participants with HAND from controls and unimpaired HIV-infected participants. These metrics, along with measures of local spontaneous neural activity, may hold promise as early markers of cognitive decline in participants with HIV infection and be useful prognostic indicators for HAND.

Polarity-dependent modulation of multi-spectral neuronal activity by transcranial direct current stimulation.

The ability to preferentially deploy neural resources to the visual space is an important component of normative cognitive function, however, the population-level cortical dynamics that sub-serve this ability are not fully understood. Specifically, rhythmic activity in the occipital cortices (e.g., theta, alpha, and gamma oscillations) has been strongly implicated in this cognitive process, but these neural responses are difficult to non-invasively manipulate in a systematic manner. In this study, transcranial direct-current stimulation (tDCS) was used to modulate brain activity, while high-density magnetoencephalography (MEG) was employed to quantify changes in rhythm-specific neural activity in the occipital cortices of 57 adults performing a visuospatial processing paradigm. All MEG data was analyzed using advanced source reconstruction and oscillatory analysis methods. Our results indicated that basal levels of occipital alpha activity were increased by an occipital-anodal/supraorbital-cathodal tDCS montage, while basal gamma levels in the same cortices were decreased by tDCS using the same montage with its polarity reversed (occipital-cathodal/supraorbital-anodal). In other words, stimulation with the occipital-anodal montage increased local spontaneous alpha (10-16 Hz) activity, while stimulation with the occipital-cathodal montage selectively decreased local gamma (64-90 Hz) activity. Neither polarity affected stimulus-induced oscillations in the alpha or gamma range. Additionally, these modulations strongly predicted the subsequent formation of fronto-visual functional connectivity within distinct oscillatory rhythms, as well as behavior on the visuospatial discrimination task. These findings provide insight into the multifaceted effects of tDCS on cortical activity, as well as the dynamic oscillatory coding of salient information in the human brain.

Roadmap for optimizing the clinical utility of emotional stress paradigms in human neuroimaging research.

The emotional stress response is relevant to a number of psychiatric disorders, including posttraumatic stress disorder (PTSD) in particular. Research using neuroimaging methods such as functional magnetic resonance imaging (fMRI) to probe stress-related neural processing have provided some insights into psychiatric disorders. Treatment providers and individual patients would benefit from clinically useful fMRI paradigms that provide information about patients' current brain state and responses to stress in order to inform the treatment selection process. However, neuroimaging has not yet made a meaningful impact on real-world clinical practice. This lack of clinical utility may be related to a number of basic psychometric properties that are often overlooked during fMRI task development. The goals of the current review are to discuss important methodological considerations for current human fMRI stress-related paradigms and to provide a roadmap for developing methodologically sound and clinically useful paradigms. This would include establishing various aspects of reliability, including internal consistency, test-retest and multi-site, as well as validity, including face, content, construct, and criterion. In addition, the establishment of standardized normative data from a large sample of participants would support our understanding of how any one individual compares to the general population. Addressing these methodological gaps will likely have a powerful effect on improving the replicability of findings and optimize our chances for improving real-world clinical outcomes.