Neural correlates of script-driven imagery in adolescents with interpersonal traumatic experiences: A pilot study.

In adults, trauma imagery has proven to be a useful tool to assess the neural mechanisms of psychological trauma processing. In adolescents, heterogeneous results could be found for other tasks, however, a trauma imagery paradigm has not been evaluated. For this purpose, we investigated a trauma imagery paradigm with control scripts to assess neural correlates of traumatic experiences in youth. 15 adolescents, who had experienced a traumatic interpersonal event in the past and have developed clinically relevant symptoms, underwent an fMRI scan while listening to their individual trauma- versus two control scripts (positive/negative). We analysed a parametric contrast of the imagery phases (trauma > negative > positive) which revealed activity in the thalamus, dorsal anterior cingulate cortex, cuneus, dorsomedial prefrontal cortex and amygdala. Additionally, amygdala-activity correlated positively with depression-symptom-severity. Our data provide evidence for the feasibility of fMRI during a trauma imagery task in adolescents to investigate networks previously related to hyperarousal in adults with PTSD. Further, we demonstrate the specificity of the activated networks for trauma imagery as compared to imagery of other emotional situations. The task might be particularly useful to evaluate neural correlates of treatment in adolescents when hyperarousal is a target symptom.

Successful group psychotherapy of depression in adolescents alters fronto-limbic resting-state connectivity.

BACKGROUND: Current resting state imaging findings support suggestions that the neural signature of depression and therefore also its therapy should be conceptualized as a network disorder rather than a dysfunction of specific brain regions. In this study, we compared neural connectivity of adolescent patients with depression (PAT) and matched healthy controls (HC) and analysed pre-to-post changes of seed-based network connectivities in PAT after participation in a cognitive behavioral group psychotherapy (CBT). METHODS: 38 adolescents (30 female; 19 patients; 13-18 years) underwent an eyes-closed resting-state scan. PAT were scanned before (pre) and after (post) five sessions of CBT. Resting-state functional connectivity was analysed in a seed-based approach for right-sided amygdala and subgenual anterior cingulate cortex (sgACC). Symptom severity was assessed using the Beck Depression Inventory Revision (BDI-II). RESULTS: Prior to group CBT, between groups amygdala and sgACC connectivity with regions of the default mode network was stronger in the patients group relative to controls. Within the PAT group, a similar pattern significantly decreased after successful CBT. Conversely, seed-based connectivity with affective regions and regions processing cognition and salient stimuli was stronger in HC relative to PAT before CBT. Within the PAT group, a similar pattern changed with CBT. Changes in connectivity correlated with the significant pre-to-post symptom improvement, and pre-treatment amygdala connectivity predicted treatment response in depressed adolescents. LIMITATIONS: Sample size and missing long-term follow-up limit the interpretability. CONCLUSIONS: Successful group psychotherapy of depression in adolescents involved connectivity changes in resting state networks to that of healthy controls.

Neural correlates of successful psychotherapy of depression in adolescents.

BACKGROUND: While major effort has been put in investigating neural correlates of depression and its treatment in adults, less is known about the effects of psychotherapy in adolescents. Given the concordance of the ventral striatum, amygdala, hippocampus and the subgenual anterior cingulate cortex (sgACC) as correlates of depression and their involvement in reward processing, we used functional magnetic resonance imaging (fMRI) during performance of a monetary reward task in an intervention versus waitlist-control design to investigate the clinical and neural effects of cognitive behavioral group therapy (CBT-G). METHODS: 22 medication naïve adolescents with major depressive disorder were scanned before and after five sessions of CBT-G (PAT-I), or before and after five weeks of waiting (PAT-W). Changes in symptom scales were analyzed along with neural activation changes within the amygdala, hippocampus, sgACC and ventral striatum regions of interest (ROI). RESULTS: Psychometric assessments and ROI activation remained unchanged in PAT-W. In PAT-I, significant reduction in clinical symptoms accompanied significant changes in brain activation within the left amygdala, left hippocampus and bilateral sgACC. In line with previous findings in adults, pre-to-post-activation changes in the bilateral sgACC correlated with pre-to-post and pre-to-follow-up symptom improvement, and individual expressions of sgACC activation before treatment were related to pre-to-follow-up therapeutic success. LIMITATIONS: Future studies should include larger sample sizes. CONCLUSIONS: Successful group psychotherapy of depression in adolescents was related to signal changes in brain regions previously demonstrated to be reliably linked with successful, particularly pharmacological treatment in adults.

Polymorphism in the µ-opioid receptor gene (OPRM1) modulates neural processing of physical pain, social rejection and error processing.

Variations of the µ-opioid receptor gene OPRM1 have been shown to modulate pain perception with some evidence pointing towards a modulation of not only physical but also "psychological pain". In line with suggestions of a common neural network involved in the processing of physical pain and negative and distressing stimuli, like social rejection as a psychologically harmful event, we examined the influence of the A118G polymorphism on the neural processing of physical and non-physical pain. Using fMRI, we investigated a sample of 23 females with the more frequent AA genotype, and eight females with the relatively rare but more pain-sensitive AG genotype during electrical stimulation to the dorsum of the non-dominant hand. Non-physical pain was investigated using Cyberball, a virtual ball-tossing game, to induce experiences of non-self-dependent social rejection. A Go/NoGo task with an increased risk of self-dependent erroneous performance was used as a control task to investigate the effects of negative feedback as a more cognitive form of distress. Relative to A118G homozygous A-allele carriers, G-allele carriers showed significantly increased activation of the supplementary motor area/superior frontal gyrus and the precentral gyrus during electrical stimulation. Increased activation of the secondary sensorimotor cortex (SII) was found during social exclusion and during negative feedback. We demonstrate that brain regions particularly related to the somatosensory component of pain processing are modulated by variations in OPRM1. Influences were evident for both physical and psychological pain processing supporting the assumption of shared neural pathways.

High field FMRI reveals thalamocortical integration of segregated cognitive and emotional processing in mediodorsal and intralaminar thalamic nuclei.

Thalamocortical loops, connecting functionally segregated, higher order cortical regions, and basal ganglia, have been proposed not only for well described motor and sensory regions, but also for limbic and prefrontal areas relevant for affective and cognitive processes. These functions are, however, more specific to humans, rendering most invasive neuroanatomical approaches impossible and interspecies translations difficult. In contrast, non-invasive imaging of functional neuroanatomy using fMRI allows for the development of elaborate task paradigms capable of testing the specific functionalities proposed for these circuits. Until recently, spatial resolution largely limited the anatomical definition of functional clusters at the level of distinct thalamic nuclei. Since their anatomical distinction seems crucial not only for the segregation of cognitive and limbic loops but also for the detection of their functional interaction during cognitive-emotional integration, we applied high resolution fMRI on 7 Tesla. Using an event-related design, we could isolate thalamic effects for preceding attention as well as experience of erotic stimuli. We could demonstrate specific thalamic effects of general emotional arousal in mediodorsal nucleus and effects specific to preceding attention and expectancy in intralaminar centromedian/parafascicular complex. These thalamic effects were paralleled by specific coactivations in the head of caudate nucleus as well as segregated portions of rostral or caudal cingulate cortex and anterior insula supporting distinct thalamo-striato-cortical loops. In addition to predescribed effects of sexual arousal in hypothalamus and ventral striatum, high resolution fMRI could extent this network to paraventricular thalamus encompassing laterodorsal and parataenial nuclei. We could lend evidence to segregated subcortical loops which integrate cognitive and emotional aspects of basic human behavior such as sexual processing.

[Polyneuropathy and monoclonal IgG/IgA gammopathy--differential neurography on the basis of two patient cases]. / Polyneuropathie und monoklonale IgG/IgA-Gammopathie--differenzielle Neurografie anhand von zwei Fallbeispielen.

With higher age, monoclonal gammopathies are more frequently diagnosed as the underlying cause of polyneuropathies. Whereas in approximately one-third of the patients, the gammopathy is related to multiple myeloma, lymphoma, other lymphoproliferative diseases, or amyloidosis, the remaining patients are diagnosed with monoclonal gammopathy of undetermined significance (MGUS). As underlined by the two reported cases, in IgG/IgA-type gammopathies electrophysiological findings of axonal lesions in mildly impaired patients are more likely to be found in patients with MGUS, while demyelinating polyneuropathies with more severe clinical impairment are more commonly seen in myeloma patients.

Antidepressant effects of augmentative transcranial magnetic stimulation: randomised multicentre trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a new treatment option for depression. Previous studies were performed with low sample sizes in single centres and reported heterogeneous results. AIMS: To investigate the efficacy of rTMS as augmentative treatment in depression. METHOD: In a randomised, double-blind, sham-controlled multicentre trial 127 patients with moderate to severe depressive episodes were randomly assigned to real or sham stimulation for 3 weeks in addition to simultaneously initiated antidepressant medication. RESULTS: We found no difference in the responder rates of the real and the sham treatment groups (31% in each) or in the decrease of the scores on the depression rating scales. CONCLUSIONS: The data do not support previous reports from smaller samples indicating an augmenting or accelerating antidepressant effect of rTMS. Further exploration of the possible efficacy of other stimulation protocols or within selected sub-populations of patients is necessary.

Verbal storage in a premotor-parietal network: evidence from fMRI-guided magnetic stimulation.

Phonological rehearsal helps to keep selected information consciously in mind for further processing. This part of short-term storage takes place during the delay period of verbal working memory tasks and involves a frontoparietal network as functional magnetic resonance imaging (fMRI) studies have shown. The involved cortical areas can be further investigated by interfering with the local information processing using transcranial magnetic stimulation (TMS). On a single subject level, we identified predominantly left-sided premotor, prefrontal, and parietal areas active during the delay period of a verbal working memory task using event-related fMRI. In a pilot approach, TMS was neuronavigated to the individually active areas by using a stereotaxic device. Then, TMS was applied during the delay period of similar tasks as in fMRI. Error rates increased significantly upon stimulating left premotor cortex, but not upon parietal or prefrontal stimulation. The contribution of the premotor cortex to storage and rehearsal is discussed as an active top-down storage process within the frontoparietal network.