Belief Updating during Social Interactions: Neural Dynamics and Causal Role of Dorsomedial Prefrontal Cortex.

In competitive interactions, humans have to flexibly update their beliefs about another person's intentions in order to adjust their own choice strategy, such as when believing that the other may exploit their cooperativeness. Here we investigate both the neural dynamics and the causal neural substrate of belief updating processes in humans. We used an adapted prisoner's dilemma game in which participants explicitly predicted the coplayer's actions, which allowed us to quantify the prediction error between expected and actual behavior. First, in an EEG experiment, we found a stronger medial frontal negativity (MFN) for negative than positive prediction errors, suggesting that this medial frontal ERP component may encode unexpected defection of the coplayer. The MFN also predicted subsequent belief updating after negative prediction errors. In a second experiment, we used transcranial magnetic stimulation (TMS) to investigate whether the dorsomedial prefrontal cortex (dmPFC) causally implements belief updating after unexpected outcomes. Our results show that dmPFC TMS impaired belief updating and strategic behavioral adjustments after negative prediction errors. Taken together, our findings reveal the time course of the use of prediction errors in social decisions and suggest that the dmPFC plays a crucial role in updating mental representations of others' intentions.

Dorsomedial prefrontal cortex repetitive transcranial magnetic stimulation for treatment-refractory major depressive disorder: A three-arm, blinded, randomized controlled trial.

BACKGROUND: Dorsomedial prefrontal cortex (DMPFC) repetitive transcranial magnetic stimulation (rTMS) is a novel intervention for treatment-refractory depression (TRD). To date, many open-label case series and one randomized controlled trial of modest sample size have provided preliminary evidence that DMPFC-rTMS is an effective treatment for TRD. Here, we report the results of a large, double-blinded, sham-controlled trial of DMPFC-rTMS for TRD. OBJECTIVE: The primary aim of this study was to determine the efficacy of DMPFC-rTMS for TRD under sham-controlled conditions. METHODS: 120 TRD patients were randomized to receive 30 twice-daily sessions of either active high-frequency, active low-frequency, or sham DMPFC-rTMS using a novel bent active/sham double-cone coil. Placebo stimulation also involved the use of surface electrodes placed above the eyebrows. The 17-item Hamilton Rating Scale for Depression served as the primary outcome measure. RESULTS: Although there was a significant main effect of treatment across all arms, active DMPFC-rTMS was not superior to sham. Both participants and assessors were unable to accuracy determine whether patients received active or placebo stimulation. However, technicians' treatment arm guesses were significantly above chance. CONCLUSION: DMPFC rTMS did not result in improvement of depressive symptoms greater than sham stimulation. We cannot rule out that the sham apparatus may also have elicited an antidepressant effect via electrical trigeminal stimulation; future DMPFC-rTMS trials are therefore warranted.

The serotonin transporter gene variants modulate acute stress-induced hippocampus and dorsomedial prefrontal cortex activity during memory retrieval.

The short (s) allele of a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is related to reduced serotonin transporter efficiency and an increased vulnerability to stress and mental disorders. In the present study, we investigated how 5-HTTLPR impacts on memory retrieval under stress and related neural activity by reanalyzing a small genetic neuroimaging data set. Twenty-seven healthy male volunteers participated in both the Trier Social Stress Test (TSST) and a respective control procedure and then their brain activity was measured with functional MRI (fMRI) while they performed an emotional-face-recognition task. Sixteen participants were carriers of the short allele (ss/sl carriers) and 11 were homozygous for the long allele (ll carriers). Genotype groups were compared with respect to stress-related physiological changes, memory performance, and brain activity. No significant genotype-dependent effects on memory performance or cortisol levels were found. The ss/sl carriers showed significantly higher systolic and diastolic blood pressure than the ll carriers, independent of stress. The ss/sl carriers reported stronger stress-induced nervous mood than the ll carriers. Our fMRI data revealed that the ss/sl carriers showed significantly weaker left hippocampus activation and stronger dorsomedial prefrontal cortex (dmPFC) deactivation when retrieving memories under stress as compared with the ll carriers. Subsequent analyses revealed that the distinct hippocampal activation pattern in both genotypes was associated with stress-induced cortisol elevation, while the distinct dmPFC activation pattern in both genotypes was associated with stress-induced changes in reaction times. Our results thus add new evidence that serotonin signaling modulates neural activity in the hippocampus and dmPFC during memory retrieval under acute psychosocial stress.

Depression alters maternal extended amygdala response and functional connectivity during distress signals in attachment relationship.

Maternal attachment-related parenting behaviors require mothers to regulate self-related and child-related distress. Emotion regulation is, in turn, influenced by maternal mood and personal developmental history. In the current study we examined how depressive mood may alter maternal limbic system function and functional connectivity underlying defensive and hedonic motivations. Twenty nine mothers were recruited to undergo a baby-cry task during a functional magnetic resonance imaging (fMRI) scan. Based on self-reported depression symptoms and clinical interview, the participants were grouped as healthy controls (n=15) and currently depressed (n=14). In the baby-cry task, 30s-long auditory stimuli of baby-cry sounds were presented to simulate four conditions: generic baby-cry (Just-Listen), baby-cry as if it were their own child's cry (Your-Baby), baby-cry as if it were themselves (Self), and matched control sounds (Noise). Depressed mothers, as compared to healthy controls, showed greater Self versus Just-Listen responses in left extended amygdala and decreased functional coupling between this left extended amygdala as the seed and nucleus accumbens (NAc) in self-oriented (Self versus Just-Listen) and child-oriented (Your-Baby versus Just-Listen) distress signals. Moreover, the extended amygdala's differential functional connectivity with dorsomedial prefrontal cortex (dmPFC) during the Your-Baby versus Self was increased for depressed mothers and decreased for healthy controls. Thus, depression may affect mothers by increasing baby-cry threat responses and dysregulating associations between threat and heathy child-oriented parenting motivations. These results are discussed in the context of attachment and self-psychology.

Cognitive safety of dorsomedial prefrontal repetitive transcranial magnetic stimulation in major depression.

The most widely used target for repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression (TRD) is the dorsolateral prefrontal cortex (DLPFC). Despite convergent evidence that the dorsomedial prefrontal cortex (DMPFC) may be a promising alternative target for rTMS in TRD, its cognitive safety profile has not previously been assessed. Here, we applied 20 sessions of rTMS to the DMPFC in 21 TRD patients. Before and after treatment, a battery of neuropsychological tasks was administered to evaluate changes in cognition across three general cognitive domains: learning and memory, attention and processing speed, and cognitive flexibility. Subjects also completed the 17-item Hamilton Rating Scale for Depression (HamD17) prior to and following treatment to measure changes in severity of depressive symptoms, and to assess the relationship between mood and cognitive performance over the course of treatment. No serious adverse effects or significant deterioration in cognitive performance were observed. Overall, subjects improved significantly on Stroop Inhibition/Switching and on Trails B, and this improvement was independent of the degree of improvement in depression symptoms. No domains or items significantly predicted clinical outcome, with the exception of baseline performance on Visual Elevator Accuracy. Clinical improvement correlated to improved performance in the overall domain of attention and processing speed, although this effect was not evident following covariate adjustment. DMPFC-rTMS did not produce any detectable cognitive adverse effects during treatment of TRD. Performance did not deteriorate significantly on any measures. Taken together, the present findings support the tolerability and cognitive safety of DMPFC-rTMS in refractory depression.

Structural Neural Substrates of Reading the Mind in the Eyes.

The ability to read the minds of others in their eyes plays an important role in human adaptation to social environments. Behavioral studies have resulted in the development of a test to measure this ability (Reading the Mind in the Eyes Test, revised version; Eyes Test), and have demonstrated that this ability is consistent over time. Although functional neuroimaging studies revealed brain activation while performing the Eyes Test, the structural neural substrates supporting consistent performance on the Eyes Test remain unclear. In this study, we assessed the Eyes Test and analyzed structural magnetic resonance images using voxel-based morphometry (VBM) in healthy participants. Test performance was positively associated with the gray matter volumes of the dorsomedial prefrontal cortex, inferior parietal lobule (temporoparietal junction), and precuneus in the left hemisphere. These results suggest that the fronto-temporoparietal network structures support the consistent ability to read the mind in the eyes.