ObjectivesPost-traumatic stress disorder (PTSD) is a common psychiatric disease with changes in neural circuitries. Neurobiological models conceptualize the symptoms of PTSD as correlates of a dysfunctional stress reaction to traumatic events. Functional imaging studies showed an increased amygdala and a decreased prefrontal cortex response in PTSD patients. As psychotherapeutic approaches represent the gold standard for PTSD treatment, it is important to examine its underlying neurobiological correlates.MethodsStudies published until August 2016 were selected through systematic literature research in the databases PubMed, PsychInfo, and Cochrane Library’s Central Register of Controlled Trials or were identified manually by searching reference lists of selected articles. Search terms were “neural correlates” OR “fMRI” OR “SPECT,” AND “therapy” AND “PTSD.” A total of 19 articles were included in the present review whereof 15 studies compared pre-to-post-therapy signal changes, six studies related pre-treatment activity to pre-to-post-symptom improvement, and four studies compared neural correlates of responders versus non-responders. The disposed therapy forms were cognitive behavioral therapy (CBT), eye movement desensitization and reprocessing, cognitive therapy, exposure therapy, mindfulness-based intervention, brief eclectic psychotherapy, and unspecified therapy.ResultsSuccessful psychotherapy of PTSD was repeatedly shown to be accompanied by decreased activity in the amygdala and the insula as well as increased activity in the dorsal anterior cingulate cortex (dACC) and hippocampus. Elevated dACC activity prior to treatment was related to subsequent treatment success and a positive predictor for treatment response. Elevated amygdala and insula pre-treatment activities were related to treatment failure.DiscussionDecreased activity in limbic brain regions and increased activity in frontal brain areas in PTSD patients after successful psychotherapeutic treatment might reflect regained top-down control over previously impaired bottom-up processes.

Functional compensation demonstrated as mechanism to offset neuronal loss in early Alzheimer disease may also occur in other adult-onset neurodegenerative diseases, particularly Huntington disease (HD) with its genetic determination and gradual changes in structural integrity. In HD, neurodegeneration typically initiates in the dorsal striatum, successively affecting ventral striatal areas. Investigating carriers of the HD mutation with evident dorsal, but only minimal or no ventral striatal atrophy, we expected to find evidence for compensation of ventral striatal functioning. We investigated 14 pre- or early symptomatic carriers of the mutation leading to HD and 18 matched healthy controls. Participants underwent structural T1 magnetic resonance imaging (MRI) and functional MRI during a reward task that probes ventral striatal functioning. Motor functioning and attention were assessed with reaction time (RT) tasks. Structural images confirmed a specific decrease of dorsal striatal but only marginal ventral striatal volume in HD relative to control subjects, paralleling prolonged RT in the motor response tasks. While behavioral performance in the reward task during fMRI scanning was unimpaired, reward-related fMRI signaling in the HD group was differentially enhanced in the bilateral ventral striatum and in bilateral orbitofrontal cortex/anterior insula, as another region sensitive to reward processing. We provide evidence for the concept of functional compensation in premanifest HD which may suggest a defense mechanism in neurodegeneration. Given the so far inevitable course of HD with its genetically determined endpoint, this disease may provide another model to study the different aspects of the concept of functional compensation.

Background: Investigating adolescents and young adults may provide a unique opportunity to understand developmental aspects of the neurobiology of depression. During adolescence, a considerable physiologic reorganization of both grey and white matter of the brain takes place, and it has been suggested that differences in grey-matter volumes during adolescence may reflect different maturational processes. Methods: We investigated grey-matter volumes in a comparatively large sample (n = 103) of adolescents and young adults (aged 12 to 27 years), 60 of them with a diagnosis of current depression. Results: Replicating previous studies, we found a clear wholebrain effect of age: the older the participants, the lower their global grey-matter volumes, particularly in the paracingulate and prefrontal cortices. Contrasting depressed and healthy youth in a whole-brain approach, we found greater grey-matter volumes in the dorsolateral prefrontal cortex of those with depression. Furthermore, a region-of-interest analysis indicated lower grey-matter volumes in the hippocampus in participants with depression compared with healthy controls. Limitations: The present study was limited because of a skewed sex distribution, its cross-sectional design and the fact that some participants were taking an antidepressant. Conclusion: During adolescence, restructuring of the brain is characterized by marked decreases in prefrontal grey-matter volumes, interpreted as a correlate of brain maturation. Findings of greater volumes in the prefrontal cortex, particularly in younger adolescents with depression, may suggest that these participants were more prone to delayed brain maturation or increased neuroplasticity. This finding may represent a risk factor for depression or constitute an effect of developing depression.

Human sexual behavior is mediated by a complex interplay of cerebral and spinal centers, as well as hormonal, peripheral, and autonomic functions. Neuroimaging studies identified central neural signatures of human sexual responses comprising neural emotional, motivational, autonomic, and cognitive components. However, empirical evidence regarding the neuromodulation of these neural signatures of human sexual responses was scarce for decades. Pharmacological functional magnetic resonance imaging (fMRI) provides a valuable tool to examine the interaction between neuromodulator systems and functional network anatomy relevant for human sexual behavior. In addition, this approach enables the examination of potential neural mechanisms regarding treatment-related sexual dysfunction under psychopharmacological agents. In this article, we introduce common neurobiological concepts regarding cerebral sexual responses based on neuroimaging findings and we discuss challenges and findings regarding investigating the neuromodulation of neural sexual stimulus processing. In particular, we summarize findings from our research program investigating how neural correlates of sexual stimulus processing are modulated by serotonergic, dopaminergic, and noradrenergic antidepressant medication in healthy males.

The clinical presentation of major depression (MD) is heterogenous and comprises various affective and cognitive symptoms including an increased sensitivity to errors. Various electrophysiological but only few functional magnetic resonance imaging (fMRI) studies investigated neural error processing in MD with inconsistent findings. Thus, reliable evidence regarding neural signatures of error processing in patients with current MD is limited despite its potential relevance as viable neurobiological marker of psychopathology. We therefore investigated a sample of 16 young adult female patients with current MD and 17 healthy controls (HC). During fMRI, we used an established Erikson-flanker Go/NoGo-paradigm and focused on neural alterations during errors of commission. In the absence of significant differences in rates of errors of commission in MD compared to HC, we observed significantly (p < 0.05, FWE-corrected on cluster level) enhanced neural activations of the dorsal anterior cingulate cortex (dACC) and the pre-supplementary motor area (pre-SMA) in MD relative to HC and thus, in brain regions consistently associated to neural error processing and corresponding behavioral adjustments. Considering comparable task performance, in particular similar commission error rates in MD and HC, our results support the evidence regarding an enhanced responsivity of neural error detection mechanisms in MD as a potential neural signature of increased negative feedback sensitivity as one of the core psychopathological features of this disorder.

Humans engage in social interactions and have a fundamental need and motivation to establish and maintain social connections. Neuroimaging studies particularly focused on the neural substrates of social exclusion in healthy subjects (HC), borderline personality disorder (BPD), and major depression (MD). However, there is evidence regarding neural alterations also during social inclusion in BPD that we intended to elucidate in our study. Considering that patients with BPD often have comorbid MD, we investigated patients with BPD, and comorbid MD, patients with MD without BPD, and a sample of HC. By investigating these two clinical samples within one study design, we attempted to disentangle potential confounds arising by psychiatric disorder or medication and to relate neural alterations under social inclusion specifically to BPD. We investigated 48 females (15 BPD and MD, 16 MD, and 17 HC) aged between 18 and 40 years by fMRI (3T), using the established cyberball paradigm with social exclusion, inclusion, and passive watching conditions. Significant group-by-condition interaction effects (p < 0.05, FWE-corrected on cluster level) were observed within the dorsolateral (dlPFC) and dorsomedial prefrontal cortex (dmPFC), the temporo-parietal junction (TPJ), the posterior cingulate cortex (PCC), and the precuneus. Comparisons of estimated neural activations revealed that significant interaction effects were related to a relative increase in neural activations during social inclusion in BPD. In detail, we observed a significant increase in differential (social inclusion vs. passive watching) neural activation within the dmPFC and the PCC in BPD compared to both, MD and HC. However, significant interaction effects within the dlPFC and the TPJ could not specifically be linked to BPD considering that they did not differ significantly between the two clinical groups in post-hoc comparisons. Our study supports previous results on effects of social and inclusion in BPD, and provides further evidence regarding disorder specific neural alterations in BPD for brain regions associated with self-referential and mentalizing processes during social inclusion.

An altered processing of negative salient stimuli has been suggested to play a central role in the pathophysiology of major depression (MD). Besides negative affective and social stimuli, physical pain as a subtype of negative sensory stimulation has been investigated in this context. However, the few neuroimaging studies on unpleasant sensory stimulation or pain processing in MD report heterogeneous findings. Here, we investigated 47 young females, 22 with MD and 25 healthy controls (HC) using fMRI (3.0 T). Four levels of increasingly unpleasant electrical stimulation were applied. Ratings of stimulus intensity were assessed by a visual analogue scale. fMRI-data were analyzed using a 2 × 4 ANOVA. Behavioral results revealed no group differences regarding accuracy of unpleasant stimulation level ratings and sensitivity to stimulation. Regarding neural activation related to increasing levels of unpleasant stimulation, we observed increasing activation of brain regions related to the pain and salient stimulus processing corresponding to increasingly unpleasant stimulation in controls. This modulation was significantly smaller in MD compared to controls, particularly in the dorsal anterior cingulate cortex, the somatosensory cortex, and the posterior insula. Overall, brain regions associated with the processing of unpleasant sensory stimulation, but also associated with the salience network, were highly reactive but less modulated in female patients with MD. These results support and extent findings on altered processing of salience and of negative sensory stimuli even of a non-painful quality in female patients with MD.

Borderline Personality Disorder (BPD) is clinically characterized by emotional instability, interpersonal disturbances and dysfunctional behavior such as non-suicidal self-injury (NSSI). During NSSI, patients with BPD typically report analgesic or hypoalgesic phenomena, and pain perception and pain processing in BPD have been repeatedly investigated. Most of the studies so far focused on affective-motivational and cognitive-evaluative neural components of pain within categorial study designs. By contrast, rather basic somatosensory aspects such as neural intensity-encoding of somatosensory stimuli were not examined in further details. Thus, we investigated patients with BPD and healthy controls (HC) by functional magnetic resonance imaging (fMRI) during an unpleasant sensory stimulation task with parametrically increasing stimulus intensities. 15 females diagnosed with BPD and 15 HCs were investigated with fMRI during four individually adjusted levels of electrical stimulus intensities. Ratings of stimulus intensity were assessed by button presses during fMRI. fMRI-data were analyzed by analyses of variances (ANOVA) at a statistical threshold of p < 0.05 FWE-corrected on cluster level. Subjective ratings of stimulus intensities were alike between BPD and HC, and intensity levels identified with equal accuracy. Significant intensity-encoding neural activations were observed within the primary and secondary somtasensory cortex, the posterior insula, the posterior midcingulate cortex (pMCC) and the supplementary motor area (SMA) in both, HC and BPD. Notably, there were no significant between-groups differences in intensity-encoding neural activations, even at lowered significance thresholds. Present results suggest a similar neural somatosensory stimulus intensity encoding in BPD as previously observed on a behavioral level. The alterations in neural affective-motivational or cognitive-evaluative components reported so far may be restricted to pain rather than unpleasant stimulus processing and were absent in our study.