Changes in resting-state functional MRI connectivity during and after transcranial direct current stimulation in healthy adults.

Introduction: Transcranial direct current stimulation (tDCS) applied over the dorsolateral prefrontal cortex (DLPFC) at rest can influence behaviors. However, its mechanisms remain poorly understood. This study examined the effect of a single session of tDCS over the bilateral DLPFC on resting-state functional connectivity using fMRI (rs-fcMRI) during and after stimulation in healthy adults. We also investigated whether baseline rs-fcMRI predicted tDCS-induced changes in rs-fcMRI. Methods: This was a randomized, sham-controlled, double-blind, crossover study. We delivered tDCS for 30 min at 1 mA with the anode and cathode over the left and right DLPFC, respectively. We used seed-based analyses to measure tDCS-induced effects on whole-brain rs-fcMRI using a 3 (before, during, after stimulation) × 2 (active, sham stimulation) ANOVA. Results: There were four significant Time × Stimulation interactions on the connectivity scores with the left DLPFC seed (under the anode electrode) and no interactions for the right DLPFC seed (under the cathode electrode). tDCS changed rs-fcMRI between the left DLPFC seed and parieto-occipital, parietal, parieto-occipitotemporal, and frontal clusters during and after stimulation, as compared to sham. Furthermore, rs-fcMRI prior to stimulation predicted some of these tDCS-induced changes in rs-fcMRI during and after stimulation. For instance, rs-fcMRI of the fronto-parietooccipital network predicted changes observed after active stimulation, rs-fcMRI of the fronto-parietal network predicted changes during active stimulation, whereas rs-fcMRI of the fronto-parieto-occipitotemporal and the frontal networks predicted changes both during and after active stimulation. Discussion: Our findings reveal that tDCS modulated rs-fcMRI both during and after stimulation mainly in regions distal, but also in those proximal to the area under the anode electrode, which were predicted by rs-fcMRI prior to tDCS. It might be worth considering rs-fcMRI to optimize response to tDCS.

Validate your white matter tractography algorithms with a reappraised ISMRM 2015 Tractography Challenge scoring system.

Since 2015, research groups have sought to produce the ne plus ultra of tractography algorithms using the ISMRM 2015 Tractography Challenge as evaluation. In particular, since 2017, machine learning has made its entrance into the tractography world. The ISMRM 2015 Tractography Challenge is the most used phantom during tractography validation, although it contains limitations. Here, we offer a new scoring system for this phantom, where segmentation of the bundles is now based on manually defined regions of interest rather than on bundle recognition. Bundles are now more reliably segmented, offering more representative metrics for future users. New code is available online. Scores of the initial 96 submissions to the challenge are updated. Overall, conclusions from the 2015 challenge are confirmed with the new scoring, but individual tractogram scores have changed, and the data is much improved at the bundle- and streamline-level. This work also led to the production of a ground truth tractogram with less broken or looping streamlines and of an example of processed data, all available on the Tractometer website. This enhanced scoring system and new data should continue helping researchers develop and evaluate the next generation of tractography techniques.

TractoInferno - A large-scale, open-source, multi-site database for machine learning dMRI tractography.

TractoInferno is the world's largest open-source multi-site tractography database, including both research- and clinical-like human acquisitions, aimed specifically at machine learning tractography approaches and related ML algorithms. It provides 284 samples acquired from 3 T scanners across 6 different sites. Available data includes T1-weighted images, single-shell diffusion MRI (dMRI) acquisitions, spherical harmonics fitted to the dMRI signal, fiber ODFs, and reference streamlines for 30 delineated bundles generated using 4 tractography algorithms, as well as masks needed to run tractography algorithms. Manual quality control was additionally performed at multiple steps of the pipeline. We showcase TractoInferno by benchmarking the learn2track algorithm and 5 variations of the same recurrent neural network architecture. Creating the TractoInferno database required approximately 20,000 CPU-hours of processing power, 200 man-hours of manual QC, 3,000 GPU-hours of training baseline models, and 4 Tb of storage, to produce a final database of 350 Gb. By providing a standardized training dataset and evaluation protocol, TractoInferno is an excellent tool to address common issues in machine learning tractography.

Whole-brain morphometry in Canadian soldiers with posttraumatic stress disorder.

Patients with posttraumatic stress disorder (PTSD) display several structural brain differences when compared with healthy individuals. However, findings are particularly inconsistent for soldiers with PTSD. Here, we characterized the brain morphometry of 37 soldiers from the Canadian Armed Forces with adulthood war-related PTSD using structural magnetic resonance imaging. We assessed time since trauma, as well as PTSD, depressive, and anxiety symptoms with the Modified PTSD Symptoms Scale, Beck Depression Inventory, and Beck Anxiety Inventory, respectively. Whole-brain morphometry was extracted with FreeSurfer and compared with a validated normative database of more than 2700 healthy individuals. Volume and thickness from several regions differed from the norms. Frontal regions were smaller and thinner, particularly the superior and rostral middle frontal gyri. Furthermore, smaller left rostral middle frontal gyrus, left pericalcarine cortex, and right fusiform gyrus were associated with more recent trauma. All subcortical structures were bigger, except the hippocampus. These findings suggest a particular brain morphometric signature of PTSD in soldiers. Smaller and thinner frontal and larger subcortical regions support impaired top-down and/or downregulation of emotional response in PTSD. Finally, the correlation of smaller frontal, temporal, and occipital regions with more recent trauma might inform future therapeutic approaches.

Concurrent Transcranial Direct Current Stimulation and Resting-State Functional Magnetic Resonance Imaging in Patients with Gambling Disorder.

Background/Introduction: Transcranial direct current stimulation (tDCS) delivered over the dorsolateral prefrontal cortex (DLPFC) while patients are at rest can decrease craving in patients with substance-related and addictive disorders. Yet, the effects of tDCS on resting-state brain activity remain unknown in this population. This study examined the effects of tDCS on resting-state functional connectivity (rsFC) with concurrent stimulation and functional magnetic resonance imaging in patients with gambling disorder. Methods: This was a randomized, sham-controlled, double-blind, crossover study. The anodal and cathodal electrodes were applied over the right and left DLPFC, respectively. Patients received 30 min of active and sham stimulation on separate days. rsFC was assessed before and during stimulation with seed-based analyses. Results: There was a significant increase of rsFC between the right DLPFC seed and the right superior parietal lobule during active stimulation as compared to during sham stimulation (p = 0.0059, corrected for multiple comparisons). There was also a positive correlation between rsFC change of this frontoparietal network and brain volume of the right DLPFC (p = 0.0042, corrected for multiple comparisons). Discussion: A single session of tDCS targeting the DLPFC strengthened functional connectivity in a frontoparietal circuit, known to be implicated in cognitive control, especially in patients with a greater volume of the region under the anode electrode. Impact statement Transcranial direct current stimulation increased the functional connectivity of a frontoparietal circuit in patients with gambling disorder. These changes were larger in patients with greater volume of the dorsolateral prefrontal cortex. Transcranial direct current stimulation strengthened the connectivity of a brain network known to be associated with cognitive control.

Brain morphometry in adults with gambling disorder.

Little is known regarding the brain substrates of Gambling Disorder, including surface brain morphometry, and whether these are linked to the clinical profile. A better understanding of the brain substrates will likely help determine targets to treat patients. Hence, the aim of this study was two-fold, that is to examine surface-based morphometry in 17 patients with gambling disorder as compared to norms of healthy individuals (2713 and 2790 subjects for cortical and subcortical anatomical scans, respectively) and to assess the clinical relevance of morphometry in patients with Gambling Disorder. This study measured brain volume, surface and thickness in Gambling Disorder. We compared these measures to those of a normative database that controlled for factors such as age and sex. We also tested for correlations with gambling-related behaviors, such as gambling severity and duration, impulsivity, and depressive symptoms (assessed using the South Oaks Gambling Screen, years of gambling, Barratt Impulsiveness Scale, and Beck Depression Inventory, respectively). Patients displayed thinner prefrontal and parietal cortices, greater volume and thickness of the occipital and the entorhinal cortices, and greater volume of subcortical regions as compared to the norms of healthy individuals. There were positive correlations between surface area of occipital regions and depressive symptoms. This work contributes to better characterize the brain substrates of Gambling Disorder, which appear to resemble those of substance use disorders and Internet Gaming Disorder.

Eye tracking of smoking-related stimuli in tobacco use disorder: A proof-of-concept study combining attention bias modification with alpha-transcranial alternating current stimulation.

BACKGROUND: Tobacco use disorder (TUD) is characterized by the presence of an attentional bias (AB) towards smoking-related stimuli. We investigated whether combining an AB modification paradigm (ABM) with transcranial alternating current stimulation (tACS) applied over the dorsolateral prefrontal cortex (DLPFC) reduces the AB towards smoking-related stimuli, as well as craving level and impulsive choices. METHODS: In a sham-controlled, crossover preliminary study, 19 subjects with TUD received two stimulation arms: 1) active tACS (10 Hz, 2 mA, 30 min) combined with ABM and 2) sham tACS combined with ABM, in a randomized order, separated by one week. AB towards smoking cues during passive observation of smoking and neutral cues was assessed with an eye-tracking device and reactions times at a visual-probe task. Craving level was measured with the Questionnaire of Smoking Urges. Impulsive choices were assessed with the delay discounting task. RESULTS: Active tACS combined with ABM reduced the amount of time spent looking at smoking-related pictures (p = 0.03), prevented the increase of self-reported desire to smoke (p = 0.026), and reduced the proportion of impulsive choices (p = 0.049), compared to sham tACS combined with ABM. No significant effects were reported on other craving dimensions and on AB based on reaction times. CONCLUSIONS: These preliminary findings suggest that combining tACS with ABM may help smokers who wish to quit by reducing the desire to smoke, attention to smoking-cues, and impulsive decision-making.

Effects of Transcranial Stimulation With Direct and Alternating Current on Resting-State Functional Connectivity: An Exploratory Study Simultaneously Combining Stimulation and Multiband Functional Magnetic Resonance Imaging.

Background: Transcranial stimulation with direct (tDCS) and alternating current (tACS) has increasingly gained interest in various fields, from cognitive neuroscience to clinical investigations. Transcranial current stimulation used alone may modulate brain activity that consequently influences behaviors, without providing information on potentially induced brain activity changes. The combination of transcranial current stimulation and functional magnetic resonance imaging (fMRI) may help to address this. This exploratory study investigated instantaneous and subsequent effects of tDCS and tACS on resting-state functional connectivity (rsFC) in healthy adults. Methods: We conducted a randomized crossover study with 15 healthy subjects receiving three stimulation conditions (tDCS, tACS, and sham) on separate days. Stimulation was applied over the left and right dorsolateral prefrontal cortex (DLPFC) for 30 min (1 mA). rsFC of the targeted prefrontal areas was assessed before, during, and after stimulation using multiband fMRI and using left and right DLPFC as seeds. Results: Both tDCS and tACS increased rsFC during and after the stimulation period, as compared to sham. tDCS-induced changes were observed between the left DLPFC and bilateral parietal regions at the junction of the superior parietal and the inferior parietal lobules. tACS-induced changes were observed between the left DLPFC and the right inferior parietal lobule. Conclusion: Overall, these results suggest that a single session with a low dose, 1 mA, of tDCS or tACS can cause changes in fronto-parietal connectivity that occur rapidly, that is, within the first 15 min. Although exploratory, this work contributes to the discussion of the potential of transcranial current stimulation to modulate resting-state networks and the interest of combining transcranial current stimulation with neuroimaging to identify these changes.

Online effects of transcranial direct current stimulation on prefrontal metabolites in gambling disorder.

Gambling disorder is characterized by persistent maladaptive gambling behaviors and is now considered among substance-related and addictive disorders. There is still unmet therapeutic need for these clinical populations, however recent advances indicate that interventions targeting the Glutamatergic/GABAergic system hold promise in reducing symptoms in substance-related and addictive disorders, including gambling disorder. There is some data indicating that transcranial direct current stimulation may hold clinical benefits in substance use disorders and modulate levels of brain metabolites including glutamate and GABA. The goal of the present work was to test whether this non-invasive neurostimulation method modulates key metabolites in gambling disorder. We conducted a sham-controlled, crossover, randomized study, blinded at two levels in order to characterize the effects of transcranial direct current stimulation over the dorsolateral prefrontal cortex on neural metabolites levels in sixteen patients with gambling disorder. Metabolite levels were measured with magnetic resonance spectroscopy from the right dorsolateral prefrontal cortex and the right striatum during active and sham stimulation. Active as compared to sham stimulation elevated prefrontal GABA levels. There were no significant changes between stimulation conditions in prefrontal glutamate + glutamine and N-acetyl Aspartate, or in striatal metabolite levels. Results also indicated positive correlations between metabolite levels during active, but not sham, stimulation and levels of risk taking, impulsivity and craving. Our findings suggest that transcranial direct current stimulation can modulate GABA levels in patients with gambling disorder which may represent an interesting future therapeutic avenue.

Semi-Automatic Segmentation of Optic Radiations and LGN, and Their Relationship to EEG Alpha Waves.

At rest, healthy human brain activity is characterized by large electroencephalography (EEG) fluctuations in the 8-13 Hz range, commonly referred to as the alpha band. Although it is well known that EEG alpha activity varies across individuals, few studies have investigated how this may be related to underlying morphological variations in brain structure. Specifically, it is generally believed that the lateral geniculate nucleus (LGN) and its efferent fibres (optic radiation, OR) play a key role in alpha activity, yet it is unclear whether their shape or size variations contribute to its inter-subject variability. Given the widespread use of EEG alpha in basic and clinical research, addressing this is important, though difficult given the problems associated with reliably segmenting the LGN and OR. For this, we employed a multi-modal approach and combined diffusion magnetic resonance imaging (dMRI), functional magnetic resonance imaging (fMRI) and EEG in 20 healthy subjects to measure structure and function, respectively. For the former, we developed a new, semi-automated approach for segmenting the OR and LGN, from which we extracted several structural metrics such as volume, position and diffusivity. Although these measures corresponded well with known morphology based on previous post-mortem studies, we nonetheless found that their inter-subject variability was not significantly correlated to alpha power or peak frequency (p >0.05). Our results therefore suggest that alpha variability may be mediated by an alternative structural source and our proposed methodology may in general help in better understanding the influence of anatomy on function such as measured by EEG or fMRI.