Targeting the prefrontal-supplementary motor network in obsessive-compulsive disorder with intensified electrical stimulation in two dosages: a randomized, controlled trial.

Obsessive-compulsive disorder (OCD) is associated with a high disease burden, and treatment options are limited. We used intensified electrical stimulation in two dosages to target a main circuitry associated with the pathophysiology of OCD, left dorsolateral prefrontal cortex (l-DLPFC), and pre-supplementary motor area (pre-SMA) and assessed clinical outcomes, neuropsychological performance, and brain physiology. In a double-blind, randomized controlled trial, thirty-nine patients with OCD were randomly assigned to three groups of sham, 2-mA, or 1-mA transcranial direct current stimulation (tDCS) targeting the l-DLPFC (F3) and pre-SMA (FC2) with anodal and cathodal stimulation respectively. The treatment included 10 sessions of 20-minute stimulation delivered twice per day with 20-min between-session intervals. Outcome measures were reduction in OCD symptoms, anxiety, and depressive states, performance on a neuropsychological test battery (response inhibition, working memory, attention), oscillatory brain activities, and functional connectivity. All outcome measures except EEG were examined at pre-intervention, post-intervention, and 1-month follow-up times. The 2-mA protocol significantly reduced OCD symptoms, anxiety, and depression states and improved quality of life after the intervention up to 1-month follow-up compared to the sham group, while the 1-mA protocol reduced OCD symptoms only in the follow-up and depressive state immediately after and 1-month following the intervention. Both protocols partially improved response inhibition, and the 2-mA protocol reduced attention bias to OCD-related stimuli and improved reaction time in working memory performance. Both protocols increased alpha oscillatory power, and the 2-mA protocol decreased delta power as well. Both protocols increased connectivity in higher frequency bands at frontal-central areas compared to the sham. Modulation of the prefrontal-supplementary motor network with intensified tDCS ameliorates OCD clinical symptoms and results in beneficial cognitive effects. The 2-mA intensified stimulation resulted in larger symptom reduction and improved more converging outcome variables related to therapeutic efficacy. These results support applying the intensified prefrontal-SMA tDCS in larger trials.

Cortical and subcortical substrates of minutes and days-long object value memory in humans.

Obtaining valuable objects motivates many of our daily decisions. However, the neural underpinnings of object processing based on human value memory are not yet fully understood. Here, we used whole-brain functional magnetic resonance imaging (fMRI) to examine activations due to value memory as participants passively viewed objects before, minutes after, and 1-70 days following value training. Significant value memory for objects was evident in the behavioral performance, which nevertheless faded over the days following training. Minutes after training, the occipital, ventral temporal, interparietal, and frontal areas showed strong value discrimination. Days after training, activation in the frontal, temporal, and occipital regions decreased, whereas the parietal areas showed sustained activation. In addition, days-long value responses emerged in certain subcortical regions, including the caudate, ventral striatum, and thalamus. Resting-state analysis revealed that these subcortical areas were functionally connected. Furthermore, the activation in the striatal cluster was positively correlated with participants' performance in days-long value memory. These findings shed light on the neural basis of value memory in humans with implications for object habit formation and cross-species comparisons.