ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Altres ajuts: Anxiety Disorders Research Network European College of Neuropsychopharmacology; Claude Leon Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 44541416-TRR58); EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant 'European and South African Research Network in Anxiety Disorders' (EUSARNAD); Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMw, 10-000-1002); Intramural Research Training Award (IRTA) program within the National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, MH002781); National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, ZIA-MH-002782); SA Medical Research Council; U.S. National Institutes of Health grants (P01 AG026572, P01 AG055367, P41 EB015922, R01 AG060610, R56 AG058854, RF1 AG051710, U54 EB020403).Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders

fMRI neurofeedback facilitates anxiety regulation in females with spider phobia

BACKGROUND: Spider phobics show an exaggerated fear response when encountering spiders. This fear response is aggravated by negative and irrational beliefs about the feared object. Cognitive reappraisal can target these beliefs, and therefore has a fear regulating effect. The presented study investigated if neurofeedback derived from functional magnetic resonance imaging (fMRI) would facilitate anxiety regulation by cognitive reappraisal, using spider phobia as a model of anxiety disorders. Feedback was provided based on activation in left dorsolateral prefrontal cortex and right insula, as indicators of engagement and regulation success, respectively. METHODS: Eighteen female spider phobics participated in a randomized, controlled, single-blinded study. All participants completed a training session in the MRI scanner. Participants assigned to the neurofeedback condition were instructed to shape their regulatory strategy based on the provided feedback. Participants assigned to the control condition were asked to adapt their strategy intuitively. RESULTS: Neurofeedback participants exhibited lower anxiety levels than the control group at the end of the training. In addition, only neurofeedback participants achieved down-regulation of insula activation levels by cognitive reappraisal. Group differences became more pronounced over time, supporting learning as a mechanism behind this effect. Importantly, within the neurofeedback group, achieved changes in insula activation levels during training predicted long-term anxiety reduction. CONCLUSIONS: The conducted study provides first evidence that fMRI neurofeedback has a facilitating effect on anxiety regulation in spider phobia

Reducing craving and consumption in individuals with drug addiction, obesity or overeating through neuromodulation intervention: a systematic review and meta-analysis of its follow-up effects

Background and aims Non-invasive brain stimulation has shown potential in clinical applications aiming at reducing craving and consumption levels in individuals with drug addiction or overeating behaviour. However, it is unclear whether these intervention effects are maintained over time. This study aimed to measure the immediate, short- and long-term effects of excitatory transcranial direct current stimulation (tDCS) and high-frequency repetitive transcranial magnetic stimulation (rTMS) targeting at dorsolateral prefrontal cortex (dlPFC) in people with drug addiction or overeating. Methods A systematic review and random effects meta-analysis. We included 20 articles (total of 22 studies using randomized controlled trials: 3 alcohol dependence, 3 drug dependence, 12 smoking, 4 overeating; total: 720 participants) from January 2000 to June 2020, which reported at least one follow-up assessment of craving, consumption or abstinence levels after the intervention. We compared effects of active versus sham stimulation immediately after the intervention and at the last follow-up assessment, as compared with baseline. Results Excitatory neuromodulation of dlPFC activity reduced craving and consumption immediately after the intervention (craving: g = 0.734, CI = 0.447-1.021, P < 0.001; consumption: g = 0.527, CI = 0.309-0.745; P < 0.001), as well as during short-, mid- and long-term abstinence (craving: g = 0.677, CI = 0.440-0.914, P < 0.001; consumption: g = 0.445, CI = 0.245-0.645, P < 0.001; abstinence levels: g = 0.698, CI = 0.433-0.963, P < 0.001; average time of follow-up: 84 +/- 83 days after last stimulation). Additional analysis demonstrated that the intervention effects were sustained in all populations studied (food, nicotine, alcohol or drug abuse) and with both stimulation techniques used (rTMS, tDCS). Interventions targeting at the left (vs right) hemisphere may be more effective. Conclusions Excitatory neuromodulation targeting the dorsolateral prefrontal cortex appears to lead to a sustained reduction of craving and consumption in individuals with addiction or overeating behaviour

Effects of single-session versus multi-session non-invasive brain stimulation on craving and consumption in individuals with drug addiction, eating disorders or obesity: A meta-analysis

Background: Brain stimulation interventions are increasingly used to reduce craving and consumption in individuals with drug addiction or excessive eating behavior. However, the efficacy of these novel treatments and whether effect sizes are affected by the length of the intervention has not been comprehensively evaluated. Objective: A meta-analytical approach was employed to evaluate the effectiveness of non-invasive excitatory brain stimulation [transcranial Direct Current Stimulation (tDCS) and high-frequency repetitive Transcranial Magnetic Stimulation (rTMS)] targeted at dorsolateral prefrontal cortex (dlPFC) for reducing craving and consumption levels in drug and eating addiction, including both single- and multi-session protocols. Methods: After a comprehensive literature search, 48 peer-reviewed studies (1095 participants in total) were included in the current meta-analysis. We computed Hedge's g as a conservative measure for evaluating effect sizes. Results: Random effects analyses revealed a small effect of neuromodulation interventions on craving and a medium effect on consumption, favoring active over sham stimulation. These effects did not differ across the different populations investigated (alcohol, nicotine, illicit drugs, eating addictions) or by the used technique (rTMS/tDCS, left/right hemisphere). Multi-session protocols showed a larger effect size for reducing craving and consumption than single-session protocols, with a positive linear association between the number of sessions or administered pulses and craving reduction, indicating a dose-response effect. Conclusions: Our results provide compelling evidence that novel non-invasive brain stimulation targeted at dlPFC reduces craving and consumption levels (providing the first meta-analytical evidence for the latter effect in drug addiction), with larger effects in multi-session as compared to single-session interventions. (C) 2018 Elsevier Inc. All rights reserved

Subtypes in addiction and their neurobehavioral profiles across three functional domains

Abstract Rates of return to use in addiction treatment remain high. We argue that the development of improved treatment options will require advanced understanding of individual heterogeneity in Substance Use Disorders (SUDs). We hypothesized that considerable individual differences exist in the three functional domains underlying addiction—approach-related behavior, executive function, and negative emotionality. We included N = 593 participants from the enhanced Nathan Kline Institute-Rockland Sample community sample (ages 18–59, 67% female) that included N = 420 Controls and N = 173 with past SUDs [54% female; N = 75 Alcohol Use Disorder (AUD) only, N = 30 Cannabis Use Disorder (CUD) only, and N = 68 Multiple SUDs]. To test our a priori hypothesis that distinct neuro-behavioral subtypes exist within individuals with past SUDs, we conducted a latent profile analysis with all available phenotypic data as input (74 subscales from 18 measures), and then characterized resting-state brain function for each discovered subtype. Three subtypes with distinct neurobehavioral profiles were recovered (p < 0.05, Cohen’s D: 0.4–2.8): a “Reward type” with higher approach-related behavior (N = 69); a “Cognitive type” with lower executive function (N = 70); and a “Relief type” with high negative emotionality (N = 34). For those in the Reward type, substance use mapped onto resting-state connectivity in the Value/Reward, Ventral-Frontoparietal and Salience networks; for the Cognitive type in the Auditory, Parietal Association, Frontoparietal and Salience networks; and for the Relief type in the Parietal Association, Higher Visual and Salience networks (p FDR < 0.05). Subtypes were equally distributed amongst individuals with different primary SUDs (χ 2 = 4.71, p = 0.32) and gender (χ 2 = 3.44, p = 0.18). Results support functionally derived subtypes, demonstrating considerable individual heterogeneity in the multi-dimensional impairments in addiction. This confirms the need for mechanism-based subtyping to inform the development of personalized addiction medicine approaches

fMRI Neurofeedback Training for Increasing Anterior Cingulate Cortex Activation in Adult Attention Deficit Hyperactivity Disorder. An Exploratory Randomized, Single-Blinded Study.

Attention Deficit Hyperactivity Disorder (ADHD) is characterized by poor cognitive control/attention and hypofunctioning of the dorsal anterior cingulate cortex (dACC). In the current study, we investigated for the first time whether real-time fMRI neurofeedback (rt-fMRI) training targeted at increasing activation levels within dACC in adults with ADHD leads to a reduction of clinical symptoms and improved cognitive functioning. An exploratory randomized controlled treatment study with blinding of the participants was conducted. Participants with ADHD (n = 7 in the neurofeedback group, and n = 6 in the control group) attended four weekly MRI training sessions (60-min training time/session), during which they performed a mental calculation task at varying levels of difficulty, in order to learn how to up-regulate dACC activation. Only neurofeedback participants received continuous feedback information on actual brain activation levels within dACC. Before and after the training, ADHD symptoms and relevant cognitive functioning was assessed. Results showed that both groups achieved a significant increase in dACC activation levels over sessions. While there was no significant difference between the neurofeedback and control group in clinical outcome, neurofeedback participants showed stronger improvement on cognitive functioning. The current study demonstrates the general feasibility of the suggested rt-fMRI neurofeedback training approach as a potential novel treatment option for ADHD patients. Due to the study's small sample size, potential clinical benefits need to be further investigated in future studies.ISRCTN12390961

Neural timescales reflect behavioral demands in freely moving rhesus macaques

Abstract Previous work demonstrated a highly reproducible cortical hierarchy of neural timescales at rest, with sensory areas displaying fast, and higher-order association areas displaying slower timescales. The question arises how such stable hierarchies give rise to adaptive behavior that requires flexible adjustment of temporal coding and integration demands. Potentially, this lack of variability in the hierarchical organization of neural timescales could reflect the structure of the laboratory contexts. We posit that unconstrained paradigms are ideal to test whether the dynamics of neural timescales reflect behavioral demands. Here we measured timescales of local field potential activity while male rhesus macaques foraged in an open space. We found a hierarchy of neural timescales that differs from previous work. Importantly, although the magnitude of neural timescales expanded with task engagement, the brain areas’ relative position in the hierarchy was stable. Next, we demonstrated that the change in neural timescales is dynamic and contains functionally-relevant information, differentiating between similar events in terms of motor demands and associated reward. Finally, we demonstrated that brain areas are differentially affected by these behavioral demands. These results demonstrate that while the space of neural timescales is anatomically constrained, the observed hierarchical organization and magnitude is dependent on behavioral demands

Sensitivity and specificity in detecting bimanual tapping.

<p>The sensitivity and specificity in detecting if a task was uni- or bimanually performed was computed using a simple threshold approach. The results for the block-wise activation-level measures from right M1 (panel <b>A</b>), and the 26-s full task correlations (panel <b>B</b>), and the 12-s steady-state task correlations (panel <b>C</b>) are presented for two participants. Each dot represents one block. Significant results are marked with an asterisk. Activation level based and overall task connectivity measures both performed well in making this binary decision, while steady-state connectivity measures performed more poorly, but still above chance level (50%) in three of five participants (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085929#pone-0085929-t002" target="_blank">table 2</a>).</p

Within-participant region-of-interest results.

<p>The individually selected regions of interest in the left and right primary motor cortices (M1) of the five participants are projected onto an average of all participants’ anatomical brain images in panel <b>A</b> (z = 51, Talairach space), and onto the individual anatomical brain images in panel <b>B</b>. In Panel <b>C</b> the BOLD responses from left M1 (averaged across all tasks) are depicted for all participants (mean ± individual SE). The time windows used to compute the block-wise correlations are superimposed on the BOLD responses. Panel <b>D</b> displays the average activation level (group mean ± group SE) during each of the sixteen experimental conditions (four different tapping sequences performed at four different speeds) in right and left M1 (group mean ± group SE), while panel E shows the results (group mean ± group SE) from the correlation analysis of the same regions of interest. From unimanual to bimanual finger tapping the average activation level increased, as expected, in the right, but not left primary motor cortex (left M1: <i>unimanual</i> 1.4%, <i>synchronous</i> 1.3%, <i>alternating</i> 1.2%, <i>unbalanced</i> 1.2%; right M1: <i>unimanual</i> −0.2%, <i>synchronous</i> 1.3%, <i>alternating</i> 1.2%, <i>unbalanced</i> 0.9%). This effect was reflected in the steady-state task and overall task connectivity (26-s full task window: <i>unimanual</i>: 0.02, <i>synchronous</i> 0.75, <i>alternating</i> 0.73, <i>unbalanced</i> 0.73; 12-s steady-state task window: <i>unimanual</i>: 0.24, <i>synchronous</i> 0.42 <i>alternating</i> 0.47, <i>unbalanced</i> 0.47,), but not visible during rest connectivity (<i>unimanual</i> 0.40, <i>synchronous</i> 0.49 <i>alternating</i> 0.48, <i>unbalanced</i> 0.48). Additionally, all task derived measures were modulated by finger tapping speed. For the activation level derived measures, this effect was most pronounced when the performed tapping sequence was easy. During steady-state connectivity the modulation by finger tapping was strongest during <i>unimanual</i>, <i>alternating</i> and <i>unbalanced</i> tapping, and for the overall task connectivity the modulation by finger tapping speed was most pronounced as tapping sequences became most difficult (<i>alternating</i> and <i>unbalanced</i> tapping).</p