The boundaries of the self: The sense of agency across different sensorimotor aspects.

The sense of agency (SoA) is the sensation of control over our actions. SoA is thought to rely mainly upon the comparison of predictions regarding the sensory outcomes of one's actions and the actual sensory outcomes. Previous studies have shown that when a discrepancy is introduced between one's actions and the sensory feedback, the reported SoA is reduced. Experimental manipulations of SoA are typically induced by introducing a discrepancy between a motor action and visual feedback of a specific sensorimotor aspect. For example, introducing a delay or a spatial deviation between the action and its sensory feedback reduces SoA. However, it is yet unclear whether the sensorimotor prediction processes underlying SoA are related between different aspects. Here in one exploratory and one preregistered experiment we tested the sense of agency across temporal, spatial, and anatomical aspects in a within-subject design. Using a novel virtual-reality task allowing the manipulation of the visual feedback of a motor action across different aspects, we show that the sensitivity of agency is different across aspects, agency judgments are correlated across aspects within subjects and bias toward attributing the viewed action to the self or to an external source is correlated as well. Our results suggest that sensorimotor prediction mechanisms underlying SoA are related between different aspects and that people have a predisposition for the directionality of agency judgments. These findings reveal the psychophysical attributes of SoA across sensorimotor aspects. Data and preregistration are available at https://goo.gl/SkbGrb.

Amygdala-derived-EEG-fMRI-pattern neurofeedback for the treatment of chronic post-traumatic stress disorder. A prospective, multicenter, multinational study evaluating clinical efficacy.

We conducted a prospective, single arm, multisite, multinational, open label trial assessing the safety and efficacy of a novel amygdala derived neurofeedback treatment, designated Amygdala-Derived-EFP, for chronic PTSD. Participants, including veterans and civilians, underwent screening, training, 15 neurofeedback sessions over 8 weeks and; baseline, termination (8 weeks) and 3 month post treatment assessments with validated measures. The primary endpoint was more than 50 % of the participants demonstrating a Minimally Clinically Important Difference (MCID) defined as a 6-point reduction, on the Clinician Administered PTSD Scale (CAPS-5) total score at 3 months. Secondary measures included the PCL-5, ERQ, PHQ-9, and CGI. Statistical analyses were performed using SAS®V9.4. The primary endpoint was met, with a CAPS-5 MCID response rate of 66.7 %. The average reduction in CAPS-5 total scores at 3 month follow up was 13.5 points, more than twice the MCID. Changes from baseline in CAPS-5, PCL-5, PHQ-9 scores at 8 weeks and the 3 month follow-up demonstrated statistically significant improvements in response and; demonstrated effect sizes ranging from 0.46 to 1.07. Adverse events were mild and resolved after treatment. This study builds on prior research demonstrating similar outcomes using amygdala-derived neurofeedback. Positive attributes of this therapy include monitoring by non-physician personnel, affordability, accessibility, and tolerability.

The bodily self from psychosis to psychedelics.

The sense of self is a foundational element of neurotypical human consciousness. We normally experience the world as embodied agents, with the unified sensation of our selfhood being nested in our body. Critically, the sense of self can be altered in psychiatric conditions such as psychosis and altered states of consciousness induced by psychedelic compounds. The similarity of phenomenological effects across psychosis and psychedelic experiences has given rise to the "psychotomimetic" theory suggesting that psychedelics simulate psychosis-like states. Moreover, psychedelic-induced changes in the sense of self have been related to reported improvements in mental health. Here we investigated the bodily self in psychedelic, psychiatric, and control populations. Using the Moving Rubber Hand Illusion, we tested (N = 75) patients with psychosis, participants with a history of substantial psychedelic experiences, and control participants to see how psychedelic and psychiatric experience impacts the bodily self. Results revealed that psychosis patients had reduced Body Ownership and Sense of Agency during volitional action. The psychedelic group reported subjective long-lasting changes to the sense of self, but no differences between control and psychedelic participants were found. Our results suggest that while psychedelics induce both acute and enduring subjective changes in the sense of self, these are not manifested at the level of the bodily self. Furthermore, our data show that bodily self-processing, related to volitional action, is disrupted in psychosis patients. We discuss these findings in relation to anomalous self-processing across psychedelic and psychotic experiences.

Differential effects of deep TMS of the prefrontal cortex on apathy and depression.

BACKGROUND: Apathy is one hallmark of major depression (MDD). It is distinguished by lack of emotion, whereas other aspects of depression involve considerable emotional distress. Investigating both apathy and depression may increase the degree of treatment efficacy for both ailments together and apart. OBJECTIVE: Evaluate the differential effects of deep transcranial magnetic stimulation (DTMS) over the prefrontal cortex (PFC) on apathy and other aspects of depression in patients suffering from a depressive episode. METHODS: Fifty-four treatment-resistant MDD patients were evaluated with the Hamilton Rating Scale for Depression (HRSD), and then treated with DTMS. Apathy-related items from HRSD (ApHRSD) were compared with the remaining items from HRSD (DepHRSD). Antidepressant medications were withdrawn and active DTMS treatment was administered at 20 Hz, 5 days a week for 4 weeks. Changes in HRSD were recorded. Primary efficacy time point was 1 week after the end of active treatment. RESULTS: At screening, ApHRSD distribution was unimodal (moderate apathy), with low correlation (r = 0.17) between ApHRSD and DepHRSD. After treatment, a third had remitted apathy, and the correlation between ApHRSD and DepHRSD had dramatically increased (r = 0.83). Severe ApHRSD (≥ 7) at screening correlated with nonremission for both ApHRSD (R(2) = 0.1993, P = .0012) and DepHRSD (R(2) = 0.0860, P = .0334). CONCLUSIONS: DTMS over the PFC improved both apathy and depression similarly. However, DTMS did not lead to MDD remission if ApHRSD at screening was ≥ 7 of 12. Further investigation using a larger sample will determine whether screening apathy at baseline could be used to predict efficacy of DTMS in MDD patients.

Deep transcranial magnetic stimulation over the prefrontal cortex: evaluation of antidepressant and cognitive effects in depressive patients.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective alternative for pharmacotherapy in treatment-resistant depressive patients, but the side effects limit its use. Transcranial magnetic stimulation (TMS) has been proposed as a refined alternative, but most studies do not indicate that TMS is as effective as ECT for severe depression. OBJECTIVE: We propose that the limited effectiveness of standard TMS resides in its superficial effect on the cortex, although much of the pathophysiology of depression is associated with deeper and larger brain regions implicated in the reward system. Herein, we tested the effectiveness and safety of a novel TMS coil, the "H-coil," which enables direct stimulation of deeper brain regions, at the expense of focality. METHODS: We have studied the antidepressant and cognitive effects induced by 4 weeks of high-frequency (20 Hz) repeated deep TMS (DTMS) over the prefrontal cortex (PFC) of 65 medication-free depressive patients, who have failed to benefit from prior medications. Patients were randomly assigned to various treatment configurations, differing in stimulation intensity and laterality. Effects were assessed by the 24-item Hamilton depression rating scale (HDRS-24) and several secondary outcome measures. RESULTS: A significant improvement in HDRS scores was found when high, but not low, stimulation intensity was used. Several cognitive improvements were evident, and no treatment-related serious adverse events were observed. CONCLUSIONS: DTMS over the PFC was found safe and effective in alleviating depression. The results accentuate the significance of deep, high-intensity stimulation over low, and serve as the first study to indicate the potential of DTMS in psychiatric and neurologic disorders.

Repetitive transcranial magnetic stimulation in the treatment of depression in adolescents: an open-label study.

OBJECTIVE: This open-label pilot study examined repetitive transcranial magnetic stimulation as a possible treatment of adolescent resistant depression. METHOD: Nine adolescents (aged 16-18 years) with severe resistant depression (determined by SCID) were recruited, and their depression, suicidality, and cognitive functions were evaluated before, during, and after a course of twenty 10-Hz, 2-second trains (intertrain intervals of 58 seconds) given over 20 min/d over 14 working days. RESULTS: Lower levels of depression with progression in therapy were recorded by both the Beck Depression Inventory and Child Depression Rating Scale measures (F1.7,14.01 = 4.52, P < 0.05; F4,32 = 6.645, P < 0.01, respectively). Three patients reached the primary outcome measure of less than 30% reduction in their Child Depression Rating Scale. The effect on suicidality was not significant. Side effects were considered mild. CONCLUSIONS: Repetitive transcranial magnetic stimulation might be a possible therapy for adolescent depression. Our preliminary findings warrant double-blind, controlled studies.