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Patients with major depressive disorder (MDD) present with heterogeneous symptom profiles, while neurobiological mechanisms are still largely unknown. Brain network studies consistently report disruptions of resting-state networks (RSNs) in patients with MDD, including hypoconnectivity in the frontoparietal network (FPN), hyperconnectivity in the default mode network (DMN), and increased connection between the DMN and FPN. Using a large, multisite fMRI dataset (n= 189 patients with MDD,n= 39 controls), we investigated network connectivity differences within and between RSNs in patients with MDD and healthy controls. We found that MDD could be characterized by a network model with the following abnormalities relative to controls: (i) lower within-network connectivity in three task-positive RSNs [FPN, dorsal attention network (DAN), and cingulo-opercular network (CON)], (ii) higher within-network connectivity in two intrinsic networks [DMN and salience network (SAN)], and (iii) higher within-network connectivity in two sensory networks [sensorimotor network (SMN) and visual network (VIS)]. Furthermore, we found significant alterations in connectivity between a number of these networks. Among patients with MDD, a history of childhood trauma and current symptoms quantified by clinical assessments were associated with a multivariate pattern of seven different within- and between-network connectivities involving the DAN, FPN, CON, subcortical regions, ventral attention network (VAN), auditory network (AUD), VIS, and SMN. Overall, our study showed that traumatic childhood experiences and dimensional symptoms are linked to abnormal network architecture in MDD. Our results suggest that RSN connectivity may explain underlying neurobiological mechanisms of MDD symptoms and has the potential to serve as an effective diagnostic biomarker.

Objectives: We aimed to examine the effects and safety of accelerated intermittent Theta Burst Stimulation (iTBS) on suicide risk in a group of treatment-resistant unipolar depressed patients, using an extensive suicide assessment scale.Methods: In 50 therapy-resistant, antidepressant-free depressed patients, an intensive protocol of accelerated iTBS was applied over the left dorsolateral prefrontal cortex (DLPFC) in a randomized, sham-controlled crossover design. Patients received 20 iTBS sessions over 4 days. Suicide risk was assessed using the Beck Scale of Suicide ideation (BSI).Results: The iTBS protocol was safe and well tolerated. We observed a significant decrease of the BSI score over time, unrelated to active or sham stimulation and unrelated to depression-response. No worsening of suicidal ideation was observed. The effects of accelerated iTBS on mood and depression severity are reported in Duprat et al. (2016). The decrease in suicide risk lasted up to 1 month after baseline, even in depression non-responders.Conclusions: This accelerated iTBS protocol was safe. The observed significant decrease in suicide risk was unrelated to active or sham stimulation and unrelated to depression response. Further sham-controlled research in suicidal depressed patients is necessary. (Clinicaltrials.gov identifier: NCT01832805).

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Background: Repetitive transcranial magnetic stimulation over the left dorsolateral prefrontal cortex (DLPFC) has been documented to influence striatal and orbitofrontal dopaminergic activity implicated in reward processing. However, the exact neuropsychological mechanisms of how DLPFC stimulation may affect the reward system and how trait hedonic capacity may interact with the effects remains to be elucidated.Objective: In this sham-controlled study in healthy individuals, we investigated the effects of a single session of neuronavigated intermittent theta burst stimulation (iTBS) on reward responsiveness, as well as the influence of trait hedonic capacity.Methods: We used a randomized crossover single session iTBS design with an interval of 1 week. We assessed reward responsiveness using a rewarded probabilistic learning task and measured individual trait hedonic capacity (the ability to experience pleasure) with the temporal experience of pleasure scale questionnaire.Results: As expected, the participants developed a response bias toward the most rewarded stimulus (rich stimulus). Reaction time and accuracy for the rich stimulus were respectively shorter and higher as compared to the less rewarded stimulus (lean stimulus). Active or sham stimulation did not seem to influence the outcome. However, when taking into account individual trait hedonic capacity, we found an early significant increase in the response bias only after active iTBS. The higher the individual's trait hedonic capacity, the more the response bias toward the rich stimulus increased after the active stimulation.Conclusion: When taking into account trait hedonic capacity, one active iTBS session over the left DLPFC improved reward responsiveness in healthy male participants with higher hedonic capacity. This suggests that individual differences in hedonic capacity may influence the effects of iTBS on the reward system.

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Inhibitory control refers to the ability to inhibit an action once it has been initiated. Impaired inhibitory control plays a key role in triggering relapse in some pathological states, such as addictions. Therefore, a major challenge of current research is to establish new methods to strengthen inhibitory control in these "high-risk" populations. In this attempt, the right inferior frontal cortex (rIFC), a neural correlate crucial for inhibitory control, was modulated using transcranial direct current stimulation (tDCS). Healthy participants (n = 31) were presented with a "Go/No-go" task, a well-known paradigm to measure inhibitory control. During this task, an event-related potential (ERP) recording (T1; 32 channels) was performed. One subgroup (n = 15) was randomly assigned to a condition with tDCS (anodal electrode was placed on the rIFC and the cathodal on the neck); and the other group (n = 16) to a condition with sham (placebo) tDCS. After one 20- minute neuromodulation session, all participants were confronted again with the same ERP Go/No-go task (T2). To ensure that potential tDCS effects were specific to inhibition, ERPs to a face-detection task were also recorded at T1 and T2 in both subgroups. The rate of commission errors on the Go/No-go task was similar between T1 and T2 in both neuromodulation groups. However, the amplitude of the P3d component, indexing the inhibition function per se, was reduced at T2 as compared with T1. This effect was specific for participants in the tDCS (and not sham) condition for correctly inhibited trials. No difference in the P3 component was observable between both subgroups at T1 and T2 for the face detection task. Overall, the present data indicate that boosting the rIFC specifically enhances inhibitory skills by decreasing the neural activity needed to correctly inhibit a response.

Although both MDD groups showed no differences in task performance, our brain imaging findings suggest that left DLPFC aiTBS treatment modulates the reward system differently according to anhedonia severity.