GnRH replacement rescues cognition in Down syndrome.

At the present time, no viable treatment exists for cognitive and olfactory deficits in Down syndrome (DS). We show in a DS model (Ts65Dn mice) that these progressive nonreproductive neurological symptoms closely parallel a postpubertal decrease in hypothalamic as well as extrahypothalamic expression of a master molecule that controls reproduction-gonadotropin-releasing hormone (GnRH)-and appear related to an imbalance in a microRNA-gene network known to regulate GnRH neuron maturation together with altered hippocampal synaptic transmission. Epigenetic, cellular, chemogenetic, and pharmacological interventions that restore physiological GnRH levels abolish olfactory and cognitive defects in Ts65Dn mice, whereas pulsatile GnRH therapy improves cognition and brain connectivity in adult DS patients. GnRH thus plays a crucial role in olfaction and cognition, and pulsatile GnRH therapy holds promise to improve cognitive deficits in DS.

Mechanisms of change in brief treatments for borderline personality disorder: a protocol of a randomized controlled trial.

BACKGROUND: Borderline personality disorder (BPD) is one of the most frequent, most debilitating and lethal mental conditions and is associated with a serious burden of disease. Treatment for patients with BPD involves structured psychotherapy, and may involve brief psychiatric treatment as first-line intervention. No controlled study has assessed the effectiveness of such brief intervention. Whereas most psychotherapy studies in patients with BPD focus on the effectiveness of the intervention, we still lack an understanding of how and why these effects are produced from a patient process perspective. It is therefore of utmost importance to study the treatment-underlying mechanisms of change. The present study plans to apply novel measurement methods for assessing change in two central psychobiological processes in BPD: emotion and socio-cognitive processing. The study uses theory-driven and ecologically valid experimental tasks, which take the patient's individual experience as the anchor, by integrating methodology from psychotherapy process and neurofunctional imagery research. METHODS: The aim of this two-arm, randomized controlled study is to test the effects (i.e., symptom reduction) and the underlying mechanisms of change associated with a brief psychiatric treatment (10 sessions over 4 months), compared with treatment as usual. Participants (N = 80 patients with BPD) undergo assessments at four points (intake, 2 months, discharge, and 12-month follow up). In addition to symptom measures, individuals undergo a 2-step assessment for the potential mechanisms of change (i.e., emotion and socio-cognitive processing): (1) behavioral and (2) (for a sub-sample) neurofunctional. We hypothesize that change in the mechanisms explains the treatment effects. DISCUSSION: This study uses an easy-to-implement treatment of BPD, and a sophisticated assessment procedure to demonstrate the critical role of psychobiological change in emotion and socio-cognitive processing in brief treatments. It will help increase the effectiveness of brief treatment for BPD and help diminish the societal burden of disease related to BPD, in these early stages of treatment. TRIAL REGISTRATION {2}: ClinicalTrials.gov: NCT03717818. Registered on 24 October 2018). Protocol version {3} number 2 from 9 February 2018.

Investigating Neuroanatomical Features in Top Athletes at the Single Subject Level.

In sport events like Olympic Games or World Championships competitive athletes keep pushing the boundaries of human performance. Compared to team sports, high achievements in many athletic disciplines depend solely on the individual's performance. Contrasting previous research looking for expertise-related differences in brain anatomy at the group level, we aim to demonstrate changes in individual top athlete's brain, which would be averaged out in a group analysis. We compared structural magnetic resonance images (MRI) of three professional track-and-field athletes to age-, gender- and education-matched control subjects. To determine brain features specific to these top athletes, we tested for significant deviations in structural grey matter density between each of the three top athletes and a carefully matched control sample. While total brain volumes were comparable between athletes and controls, we show regional grey matter differences in striatum and thalamus. The demonstrated brain anatomy patterns remained stable and were detected after 2 years with Olympic Games in between. We also found differences in the fusiform gyrus in two top long jumpers. We interpret our findings in reward-related areas as correlates of top athletes' persistency to reach top-level skill performance over years.

[Operative and perioperative aspects of deep brain stimulation]. / Aspects opératoires et péri-opératoires de la stimulation cérébrale profonde.

Deep brain stimulation (DBS) requires the surgical implantation of a system including brain electrodes and impulsion generator(s). The nuclei targeted by the stereotaxic implantation methodology have to be visualized at best by high resolution imaging. The surgical procedure for implanting the electrodes is performed if possible under local anaesthesia to make electro-physiological measurements and to test intra-operatively the effect of the stimulation, in order to optimize the position of the definitive electrode. In a second step, the impulsion generator(s) are implanted under general anaesthesia. DBS for movement disorders has a very good efficacy and a low albeit non-zero risk of serious complications. Complications related to the material are the most common.

Body context and posture affect mental imagery of hands.

Different visual stimuli have been shown to recruit different mental imagery strategies. However the role of specific visual stimuli properties related to body context and posture in mental imagery is still under debate. Aiming to dissociate the behavioural correlates of mental processing of visual stimuli characterized by different body context, in the present study we investigated whether the mental rotation of stimuli showing either hands as attached to a body (hands-on-body) or not (hands-only), would be based on different mechanisms. We further examined the effects of postural changes on the mental rotation of both stimuli. Thirty healthy volunteers verbally judged the laterality of rotated hands-only and hands-on-body stimuli presented from the dorsum- or the palm-view, while positioning their hands on their knees (front postural condition) or behind their back (back postural condition). Mental rotation of hands-only, but not of hands-on-body, was modulated by the stimulus view and orientation. Additionally, only the hands-only stimuli were mentally rotated at different speeds according to the postural conditions. This indicates that different stimulus-related mechanisms are recruited in mental rotation by changing the bodily context in which a particular body part is presented. The present data suggest that, with respect to hands-only, mental rotation of hands-on-body is less dependent on biomechanical constraints and proprioceptive input. We interpret our results as evidence for preferential processing of visual- rather than kinesthetic-based mechanisms during mental transformation of hands-on-body and hands-only, respectively.

Improved segmentation of deep brain grey matter structures using magnetization transfer (MT) parameter maps.

Basal ganglia and brain stem nuclei are involved in the pathophysiology of various neurological and neuropsychiatric disorders. Currently available structural T1-weighted (T1w) magnetic resonance images do not provide sufficient contrast for reliable automated segmentation of various subcortical grey matter structures. We use a novel, semi-quantitative magnetization transfer (MT) imaging protocol that overcomes limitations in T1w images, which are mainly due to their sensitivity to the high iron content in subcortical grey matter. We demonstrate improved automated segmentation of putamen, pallidum, pulvinar and substantia nigra using MT images. A comparison with segmentation of high-quality T1w images was performed in 49 healthy subjects. Our results show that MT maps are highly suitable for automated segmentation, and so for multi-subject morphometric studies with a focus on subcortical structures.

Transcranial ultrasound brain perfusion assessment with a contrast agent-specific imaging mode: results of a two-center trial.

BACKGROUND AND PURPOSE: The purpose of this study was to assess brain perfusion with an ultrasound contrast-specific imaging mode and to prove if the results are comparable between 2 centers using a standardized study protocol. METHODS: A total of 32 individuals without known cerebrovascular disease were included in the study. Perfusion studies were performed ipsilaterally in an axial diencephalic plane after intravenous administration of 0.75 mL of Optison. Offline time intensity curves (TIC) were generated in different anatomic regions. Both centers used identical study protocols, ultrasound machines, and contrast agent. RESULTS: In both centers, the comparison of the parameter time to peak intensity (TPI) revealed significantly shorter TPIs in the main vessel structures compared with any parenchymal region of interest (ROI), whereas no significant differences were seen between the parenchymal ROIs. The parameter peak intensity (PI) varied widely interindividually in both centers, whereas the inter-ROI comparison revealed statistical significance (P < 0.05) in most of the cases according to the following pattern: (1) lentiforme nucleus > thalamus and white matter region, (2) thalamus > white matter region, and (3) main vessel > any parenchymal structure. Similar results were achieved in both centers independently. CONCLUSIONS: The study demonstrates that brain perfusion assessment with an ultrasound contrast-specific imaging mode is comparable between different centers using the same study protocol.

Bilateral thalamic gray matter changes in patients with restless legs syndrome.

Restless legs syndrome (RLS) is a common neurological disorder of a primary unpleasant sensation with an urge to move the legs occurring at rest. The etiology of idiopathic RLS is unknown and structural cerebral abnormalities have so far not been detected. We studied 51 right-handed patients with an idiopathic restless legs syndrome in two independent samples (Regensburg RLS-group: n = 28, Munich RLS-group: n = 23) and compared them to 51 sex- and age-matched healthy volunteers. High-resolution T1-weighted magnetic resonance imaging (MRI) of each subject was obtained and analyzed using voxel-based morphometry (VBM) to detect regionally specific differences in gray matter between patients and controls. Conjunction analysis was used to combine results from both centers. In patients with idiopathic RLS, both study centers observed independently a bilateral gray matter increase in the pulvinar. In the conjunction analysis including all patients and controls from both study centers, a significant gray matter increase in the pulvinar bilaterally (right: x = 16, y = -21, z = 12, Z = 4.57; left: x = -16, y = -24, z = 12, Z = 4.10) was present. This is the first demonstration of structural changes in the brain of patients with idiopathic RLS. These changes in thalamic structures are either involved in the pathogenesis of RLS or may reflect a consequence of chronic increase in afferent input of behaviorally relevant information.