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Although abnormal resting state connectivity within several brain networks has been repeatedly reported in depression, little is known about connectivity in patients with early onset chronic depression. We compared resting state connectivity in a homogenous sample of 32 unmedicated patients with early onset chronic depression and 40 healthy control participants in a seed-to-voxel-analysis. According to previous meta-analyses on resting state connectivity in depression, 12 regions implicated in default mode, limbic, frontoparietal and ventral attention networks were chosen as seeds. We also investigated associations between connectivity values and severity of depression. Patients with chronic depression exhibited stronger connectivity between precuneus and right pre-supplementary motor area than healthy control participants, possibly reflecting aberrant information processing and emotion regulation deficits in depression. Higher depression severity scores (Hamilton Rating Scale for Depression) were strongly and selectively associated with weaker connectivity between the precuneus and the subcallosal anterior cingulate. Our findings correspond to results obtained in studies including both episodic and chronic depression. This suggests that there may be no strong differences between subtypes of depression regarding the seeds analyzed here. To further clarify this issue, future studies should directly compare patients with different courses of depression.

Background and ObjectiveBioenergetic disturbance, mainly caused by mitochondrial dysfunction, is an established pathophysiologic phenomenon in neurodegenerative movement disorders. The in vivo assessment of brain energy metabolism by31phosphorus magnetic resonance spectroscopy imaging could provide pathophysiologic insights and serve in the differential diagnosis of parkinsonian disorders. In this study, we investigated such aspects of the underlying pathophysiology in patients with idiopathic Parkinson disease (PwPD) and progressive supranuclear palsy (PwPSP).MethodsIn total, 30 PwPD, 16 PwPSP, and 25 healthy control subjects (HCs) underwent a clinical examination, structural magnetic resonance imaging, and31phosphorus magnetic resonance spectroscopy imaging of the forebrain and basal ganglia in a cross-sectional study.ResultsHigh-energy phosphate metabolites were remarkably decreased in PwPD, particularly in the basal ganglia (−42% compared with HCs and −43% compared with PwPSP,p< 0.0001). This result was not confounded by morphometric brain differences. By contrast, PwPSP had normal levels of high-energy energy metabolites. Thus, the combination of morphometric and metabolic neuroimaging was able to discriminate PwPD from PwPSP with an accuracy of up to 0.93 [95%-CI: 0.91–0.94].DiscussionOur study shows that mitochondrial dysfunction and bioenergetic depletion contribute to idiopathic Parkinson disease pathophysiology but not to progressive supranuclear palsy. Combined morphometric and metabolic imaging could serve as an accompanying diagnostic biomarker in the neuroimaging-guided differential diagnosis of these parkinsonian disorders.Classification of EvidenceThis study provides Class III evidence that31phosphorus magnetic resonance spectroscopy imaging combined with morphometric MRI can differentiate PwPD from PwPSP.

Background Thyroid hormone action is mediated by two forms of thyroid hormone receptors (α, β) with differential tissue distribution. Thyroid hormone receptor β (TRβ) mutations lead to resistance to thyroid hormone action in tissues predominantly expressing the β form of the receptor (pituitary, liver). This study seeks to identify the effects of mutant TRβ on pituitary size. Methods High-resolution 3D T1-weighted magnetic resonance images were acquired in 19 patients with RTHβ in comparison to 19 healthy matched controls. Volumetric measurements of the pituitary gland were performed independently and blinded by four different raters (two neuroradiologists, one neurologist, one neuroscientist). Results Patients with mutant TRβ (resistance to thyroid hormone β, RTHβ) showed elevated free tri-iodothyronine/thyroxine levels with normal thyroid-stimulating hormone levels, whereas healthy controls showed normal thyroid hormone levels. Imaging revealed smaller pituitary size in RTHβ patients in comparison to healthy controls (F(1,35) = 7.05, P = 0.012, partial η2 = 0.17). Conclusion RTHβ subjects have impaired sensitivity to thyroid hormones, along with decreased size of the pituitary gland.

Contains fulltext : 241328.pdf (Publisher’s version ) (Closed access) Many studies point toward volume reductions in the amygdala as a potential neurostructural marker for trait aggression. However, most of these findings stem from clinical samples, rendering unclear whether the findings generalize to non-clinical populations. Furthermore, the notion of neural networks suggests that interregional correlations in gray matter volume (i.e., structural covariance) can explain individual differences in aggressive behavior beyond local univariate associations. Here, we tested whether structural covariance between amygdala subregions and the rest of the brain is associated with self-reported aggression in a large sample of healthy young students (n = 263; 49% women). Salivary testosterone concentrations were measured for a subset of n = 40 male and n = 36 female subjects, allowing us to investigate the influence of endogenous testosterone on structural covariance. Aggressive individuals showed enhanced covariance between left superficial amygdala (SFA) and left dorsal anterior insula (dAI), but lower covariance between right laterobasal amygdala (LBA) and right dorsolateral prefrontal cortex (dlPFC). These structural patterns overlap with functional networks involved in the genesis and regulation of aggressive behavior, respectively. With increasing endogenous testosterone, we observed stronger structural covariance between right centromedial amygdala (CMA) and right medial prefrontal cortex in men and between left CMA and bilateral orbitofrontal cortex in women. These results speak for structural covariance of amygdala subregions as a robust correlate of trait aggression in healthy individuals. Moreover, regions that showed structural covariance with the amygdala modulated by either testosterone or aggression did not overlap, suggesting a complex role of testosterone in human social behavior beyond facilitating aggressiveness. 09 juli 2021 14 p.

Retrieval practice improves retention of information in long-term memory more than restudy, but the underlying neural mechanisms of this “retrieval practice effect” (RPE) remain poorly understood. Therefore, we investigated the behavioral and neural differences between previously retrieved versus restudied items at final retrieval. Thirty younger (20–30 years old) and twenty-five older (50+ years old) adults learned familiar and new picture stimuli either through retrieval or restudy. At final recognition, hemodynamic activity was measured using functional magnetic resonance imaging (fMRI). Behaviorally, younger and older adults showed similar benefits of retrieval practice, with higher recollection, but unchanged familiarity rates. In a univariate analysis of the fMRI data, activation in medial prefrontal cortex and left temporal regions correlated with an individual’s amount of behavioral benefit from retrieval practice, irrespective of age. Compatible with this observation, in a multivariate representational similarity analysis (RSA), retrieval practice led to an increase in pattern similarity for retested items in a priori defined regions of interest, including the medial temporal lobe, as well as prefrontal and parietal cortex. Our findings demonstrate that retrieval practice leads to enhanced long-term memories in younger and older adults alike, and this effect may be driven by fast consolidation processes.

We examined the effect of galvanic vestibular stimulation (GVS) on resting state brain activity using fMRI (rs‐fMRI) in patients with bilateral vestibulopathy. Based on our previous findings, we hypothesized that GVS, which excites the vestibular nerve fibers, (a) increases functional connectivity in temporoparietal regions processing vestibular signals, and (b) alleviates abnormal visual–vestibular interaction. Rs‐fMRI of 26 patients and 26 age‐matched healthy control subjects was compared before and after GVS. The stimulation elicited a motion percept in all participants. Using different analyses (degree centrality, DC; fractional amplitude of low frequency fluctuations [fALFF] and seed‐based functional connectivity, FC), group comparisons revealed smaller rs‐fMRI in the right Rolandic operculum of patients. After GVS, rs‐fMRI increased in the right Rolandic operculum in both groups and in the patients' cerebellar Crus 1 which was related to vestibular hypofunction. GVS elicited a fALFF increase in the visual cortex of patients that was inversely correlated with the patients' rating of perceived dizziness. After GVS, FC between parietoinsular cortex and higher visual areas increased in healthy controls but not in patients. In conclusion, short‐term GVS is able to modulate rs‐fMRI in healthy controls and BV patients. GVS elicits an increase of the reduced rs‐fMRI in the patients' right Rolandic operculum, which may be an important contribution to restore the disturbed visual–vestibular interaction. The GVS‐induced changes in the cerebellum and the visual cortex were associated with lower dizziness‐related handicaps in patients, possibly reflecting beneficial neural plasticity that might subserve visual–vestibular compensation of deficient self‐motion perception.

Motivational influences on cognitive control play an important role in shaping human behavior. Cognitive facilitation through motivators such as prospective reward or punishment is thought to depend on regions from the dopaminergic mesocortical network, primarily the ventral tegmental area (VTA), inferior frontal junction (IFJ), and anterior cingulate cortex (ACC). However, how interactions between these regions relate to motivated control remains elusive. In the present functional magnetic resonance imaging study, we used dynamic causal modeling (DCM) to investigate effective connectivity between left IFJ, ACC, and VTA in a task‐switching paradigm comprising three distinct motivational conditions (prospective monetary reward or punishment and a control condition). We found that while prospective punishment significantly facilitated switching between tasks on a behavioral level, interactions between IFJ, ACC, and VTA were characterized by modulations through prospective reward but not punishment. Our DCM results show that IFJ and VTA modulate ACC activity in parallel rather than by interaction to serve task demands in reward‐based cognitive control. Our findings further demonstrate that prospective reward and punishment differentially affect neural control mechanisms to initiate decision‐making., Dynamic causal modeling (DCM) in functional magnetic resonance imaging data was applied to investigate effective connectivity between left IFJ, ACC, and VTA in a task‐switching paradigm comprising three distinct motivational conditions (prospective monetary reward or punishment and a control condition). Prospective punishment significantly facilitated switching between tasks on a behavioral level, while interactions between IFJ, ACC, and VTA were characterized by modulations through prospective reward. Our DCM results show that IFJ and VTA modulate ACC activity in parallel rather than by interaction to serve task demands in reward‐based cognitive control.

Contains fulltext : 233159.pdf (Publisher’s version ) (Open Access) Winners are commonly assumed to compete more aggressively than losers. Here, we find overwhelming evidence for the opposite. We first demonstrate that low-ranking teams commit more fouls than they receive in top-tier soccer, ice hockey, and basketball men's leagues. We replicate this effect in the laboratory, showing that male participants deliver louder sound blasts to a rival when placed in a low-status position. Using neuroimaging, we characterize brain activity patterns that encode competitive status as well as those that facilitate status-dependent aggression in healthy young men. These analyses reveal three key findings. First, anterior hippocampus and striatum contain multivariate representations of competitive status. Second, interindividual differences in status-dependent aggression are linked with a sharper status differentiation in the striatum and with greater reactivity to status-enhancing victories in the dorsal anterior cingulate cortex. Third, activity in ventromedial, ventrolateral, and dorsolateral prefrontal cortex is associated with trial-wise increases in status-dependent aggressive behavior. Taken together, our results run counter to narratives glorifying aggression in competitive situations. Rather, we show that those in the lower ranks of skill-based hierarchies are more likely to behave aggressively and identify the potential neural basis of this phenomenon. 15 p.

Present project is concerned with the possibility to modulate the neural regulation of food intake by non-invasive stimulation of the vagus nerve. This nerve carries viscero-afferent information from the gut and other internal organs and therefore serves an important role in ingestive behavior. The electrical stimulation of the vagus nerve (VNS) is a qualified procedure in the treatment of drug-resistant epilepsy and depression. Since weight loss is a known common side effect of VNS treatment in patients with implanted devices, VNS is evaluated as a treatment of obesity. To investigate potential VNS-related changes in the cognitive processing of food-related items, 21 healthy participants were recorded in a 3-Tesla scanner in two counterbalanced sessions. Participants were presented with 72 food pictures and asked to rate how much they liked that food. Before entering the scanner subjects received a 1-h sham or verum stimulation, which was implemented transcutanously with a Cerbomed NEMOS® device. We found significant activations in core areas of the vagal afferent pathway, including left brainstem, thalamus, temporal pole, amygdala, insula, hippocampus, and supplementary motor area for the interaction between ratings (high vs low) and session (verum vs sham stimulation). Significant activations were also found for the main effect of verum compared to sham stimulation in the left inferior and superior parietal cortex. These results demonstrate an effect of tVNS on food image processing even with a preceding short stimulation period. This is a necessary prerequisite for a therapeutic application of tVNS which has to be evaluated in longer-term studies.

Winners are commonly assumed to compete more aggressively than losers. Here, we find overwhelming evidence for the opposite. We first demonstrate that low-ranking teams commit more fouls than they receive in top-tier soccer, ice hockey, and basketball men’s leagues. We replicate this effect in the laboratory, showing that male participants deliver louder sound blasts to a rival when placed in a low-status position. Using neuroimaging, we characterize brain activity patterns that encode competitive status as well as those that facilitate status-dependent aggression in healthy young men. These analyses reveal three key findings. First, anterior hippocampus and striatum contain multivariate representations of competitive status. Second, interindividual differences in status-dependent aggression are linked with a sharper status differentiation in the striatum and with greater reactivity to status-enhancing victories in the dorsal anterior cingulate cortex. Third, activity in ventromedial, ventrolateral, and dorsolateral prefrontal cortex is associated with trial-wise increases in status-dependent aggressive behavior. Taken together, our results run counter to narratives glorifying aggression in competitive situations. Rather, we show that those in the lower ranks of skill-based hierarchies are more likely to behave aggressively and identify the potential neural basis of this phenomenon.

In humans, food is considered a powerful primary reinforcer, whereas money is a secondary reinforcer, as it gains a value through learning experience. Here, we aimed to identify the neural regions supporting the processing of food-related reinforcers, relate it to the neural underpinnings of monetary reinforcers, and explore their modulation by metabolic state (hunger vs satiety). Twenty healthy male participants were tested in two experimental sessions, once hungry and once satiated, using functional magnetic resonance imaging. Participants performed an associative learning task, receiving food or monetary rewards (in the form of images) on separate blocks. Irrespective of incentive type, both food and monetary rewards engaged ventral striatum, medial orbitofrontal cortex and amygdala, regions that have been previously associated with reward processing. Food incentives additionally engaged the opercular part of the inferior frontal gyrus and the insula, collectively known as a primary gustatory cortex. Moreover, in response to negative feedback (here, reward omission), robust activation was observed in anterior insula, supplementary motor area and lateral parts of the prefrontal cortex, including middle and inferior frontal gyrus. Furthermore, the interaction between metabolic state and incentive type resulted in supramarginal gyrus (SMG) activity, among other motor and sensory-related regions. Finally, functional connectivity analysis showed correlation in the hungry state between the SMG and mesolimbic regions, including the hippocampus, midbrain and cingulate areas. Also, the interaction between metabolic state and incentive type revealed coupling between SMG and ventral striatum. Whereas general purpose reward-related regions process incentives of different kinds, the current results suggest that the SMG might play a key role in integrating the information related to current metabolic state and available incentive type.

The pleiotropic function of thyroid hormones (TH) is mediated by an organ specific expression of thyroid hormone transporters, deiodinases and TH receptors. In a series of studies we used the model of an experimentally induced hyper- or hypothyroidism in human volunteers to delineate TH action on the brain. A battery of neuropsychological testing paradigms was employed and complemented by structural and functional multimodal neuroimaging. Experimentally induced mild thyrotoxicosis for 6 weeks was associated with changes in brain structure (determined with voxel-based morphometry), resting state functional connectivity, and task-related functional activation in a working memory paradigm. Partial withdrawal of TH replacement in patients without thyroid (subclinical hypothyroidism) likewise lead to changes on multiple functional and structural brain measures. Importantly, the series of studies reviewed here identified the cerebellum as one crucial site of action.

Objective X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disease with adult onset dystonia and subsequent parkinsonism. Postmortem and imaging studies revealed remarkable striatal pathology, with a predominant involvement of the striosomal compartment in the early phase. Here, we aimed to disentangle sequential neurodegeneration in the striatum of XDP patients, provide evidence for preferential loss of distinct striatal areas in the early phase, and investigate whether iron accumulation is present. Methods We used multimodal structural magnetic resonance imaging (voxel-based morphometry and relaxometry) in 18 male XDP patients carrying a TAF1 mutation and 19 age-matched male controls. Results Voxel-based relaxometry and morphometry revealed (1) a cluster in the anteromedial putamen showing high iron content and severe atrophy (-55%) and (2) a cluster with reduced relaxation rates as a marker for increased water levels and a lower degree of atrophy (-20%) in the dorsolateral putamen. Iron deposition correlated with the degree of atrophy (ρ = -0.585, p = 0.011) and disease duration (ρ = 0.632, p = 0.005) in the anteromedial putamen. In the dorsolateral putamen, sensorimotor putamen atrophy correlated with disease severity (ρ = -0.649, p = 0.004). Interpretation This multimodal approach identified a patchy pattern of atrophy within the putamen. Atrophy is advanced and associated with iron accumulation in rostral regions of the striatum, whereas neurodegeneration is moderate and still ongoing in dorsolateral areas. Given the short disease duration and predominant dystonic phenotype, these results are well in line with early and preferential degeneration of striosome-rich striatal areas in XDP. ANN NEUROL 2019;86:517-526.

Objective The aim of this study was to experimentally evaluate the effects of subclinical mild hypothyroidism on brain network connectivity as determined by resting state fMRI (rsfMRI) which serves as a proxy for global changes in brain function. Methods Fifteen otherwise healthy patients with complete hypothyroidism under stable, long term levothyroxine substitution volunteered for the study. They reduced their pretest levothyroxine dosage by 30% for 52–56 days. Basally and after partial levothyroxine withdrawal, rsfMRI along with a neuropsychological analysis was performed. RsfMRI was subjected to graph-theory-based analysis to investigate whole-brain intrinsic functional connectivity. Results The desired subclinical hypothyroidism was achieved in all subjects. This was associated with a significant decrease in resting-state functional connectivity specifically in the cuneus (0.05 FWE corrected at cluster level) which was mainly caused by a weaker functional connectivity to the cerebellum and regions of the default mode network, i.e. the medial prefrontal cortex, the precuneus and the bilateral angular gyri. The decrease in cuneus connectivity was correlated to the increase in TSH serum levels. A working memory task showed a slightly longer reaction time and less accuracy after partial levothyroxine withdrawal. Conclusion Even short-term partial levothyroxine partial withdrawal leads to deficits in working memory tasks and to a weaker integration of the cuneus within the default mode network.

Hypothyroidism is associated with memory impairments. The present study aimed to evaluate the effects of partial withdrawal of levothyroxine on working memory tasks and brain function. Fifteen subjects under long-term levothyroxine substitution as a result of complete hypothyroidism participated in the present study. Functional magnetic resonance imaging (MRI) was performed using a working memory task (n-back task) and neuropsychological tests were performed before and 52-54 days after the induction of subclinical hypothyroidism by reducing the pretest levothyroxine dosage by 30%. Reaction time of subjects under partial levothyroxine withdrawal was significantly longer and less accurate with respect to solving the working memory tasks. Functional MRI revealed significant activation changes after medication withdrawal in the cerebellum, insula, parietal, frontal, temporal and occipital lobes, lingual gyrus, and the cuneus. Partial withdrawal of levothyroxine may lead to deficits in a working memory task and to an activation of brain areas associated with working memory ability.

Bilateral vestibular failure (BVF) is a severe chronic disorder of the labyrinth or the eighth cranial nerve characterized by unsteadiness of gait and disabling oscillopsia during head movements. According to animal data, vestibular input to the hippocampus is proposed to contribute to spatial memory and spatial navigation. Except for one seminal study showing the association of impaired spatial navigation and hippocampal atrophy, patient data in BVF are lacking. Therefore, we performed a voxel-wise comparison of the hippocampal gray matter volume (GMV) in a clinically representative sample of 27 patients with incomplete BVF and 29 age- and gender-matched healthy controls to test the hypothesis of hippocampal atrophy in BVF. Although the two groups did not generally differ in their hippocampal GMV, a reduction of GMV in the bilateral hippocampal CA3 region was significantly correlated with increased vestibulopathy-related clinical impairment. We propose that GMV reduction in the hippocampus of BVF patients is related to the severity of vestibular-induced disability which is in line with combined hippocampal atrophy and disorders of spatial navigation in complete vestibular deafferentation due to bilateral nerve section. Clinically, however, the most frequent etiologies of BVF cause incomplete lesions. Accordingly, hippocampus atrophy and deficits in spatial navigation occur possibly less frequently than previously suspected. Hum Brain Mapp 37:1998-2006, 2016. © 2016 Wiley Periodicals, Inc.

Background Obsessive–compulsive disorder (OCD) is a psychiatric disorder which is characterized by recurrent intrusive thoughts (obsessions) and ritualized, repetitive behaviors or mental acts (compulsions). The gold standard for the treatment of OCD is cognitive behavioral therapy (CBT) with exposure and response prevention. This is the first study exploring the predictive value of resting-state functional connectivity for the outcome of CBT. Methods We assessed whole-brain resting-state functional connectivity in a group of 17 un-medicated OCD inpatients prior to CBT compared to 19 healthy controls using functional magnetic resonance imaging. The graph theoretical metric degree centrality served as indicator for altered voxel-wise whole-brain functional connectivity. The relative change in the Yale-Brown Obsessive Compulsive Scale (YBOCS) score was used to evaluate treatment outcome. Results The degree centrality of the right basolateral nuclei group of the amygdala was positively correlated with the response to subsequent CBT. OCD patients showed a lower degree centrality of the superficial amygdala (bilateral). Conclusions Our results suggest that two different sub-regions of the amygdala and their respective neural networks are affected in OCD: the superficial amygdala and networks related to evaluation of reinforcers and risk anticipation and the basolateral amygdala which is implicated in fear processing. The diminished CBT response in patients showing a lower degree centrality of the basolateral amygdala reflects a deficient fear circuit in these patients which may impact fear extinction as a core mechanism of exposure-based CBT.

Objective: Spatial orientation and navigation depends on information from the vestibular system. Previous work suggested impaired spatial navigation in patients with bilateral vestibular failure (BVF). The aim of this study was to investigate event-related brain activity by functional magnetic resonance imaging (fMRI) during spatial navigation and visual memory tasks in BVF patients. Methods: Twenty-three BVF patients and healthy age- and gender matched control subjects performed learning sessions of spatial navigation by watching short films taking them through various streets from a driver’s perspective along a route to the Cathedral of Cologne using virtual reality videos (adopted and modified from Google Earth®). In the scanner, participants were asked to respond to questions testing for visual memory or spatial navigation while they viewed short video clips. From a similar but not identical perspective depicted video frames of routes were displayed which they had previously seen or which were completely novel to them. Results: Compared with controls, posterior cerebellar activity in BVF patients was higher during spatial navigation than during visual memory tasks, in the absence of performance differences. This cerebellar activity correlated with disease duration. Conclusions: Cerebellar activity during spatial navigation in BVF patients may reflect increased non-vestibular efforts to counteract the development of spatial navigation deficits in BVF. Conceivably, cerebellar activity indicates a change in navigational strategy of BVF patients, i.e. from a more allocentric, landmark or place-based strategy (hippocampus) to a more sequence-based strategy. This interpretation would be in accord with recent evidence for a cerebellar role in sequence-based navigation.

Background In primary biliary cholangitis (PBC) fatigue is a major clinical challenge of unknown etiology. By demonstrating that fatigue in PBC is associated with an impaired cognitive performance, previous studies have pointed out the possibility of brain abnormalities underlying fatigue in PBC. Whether structural brain changes are present in PBC patients with fatigue, however, is unclear. To evaluate the role of structural brain abnormalities in PBC patients severely affected from fatigue we, therefore, performed a case-control cerebral magnetic resonance imaging (cMRI) study and correlated changes of white and grey brain matter with the cognitive and attention performance. Methods 20 female patients with PBC and 20 female age-matched controls were examined in this study. The assessment of fatigue, psychological symptoms, cognitive and attention performance included clinical questionnaires, established cognition tests and a computerized test battery of attention performance. T1-weighted cMRI and diffusion tensor imaging (DTI) scans were acquired with a 3 Tesla scanner. Structural brain alterations were investigated with voxel-based morphometry (VBM) and DTI analyses. Results were correlated to the cognitive and attention performance. Results Compared to healthy controls, PBC patients had significantly higher levels of fatigue and associated psychological symptoms. Except for an impairment of verbal fluency, no cognitive or attention deficits were found in the PBC cohort. The VBM and DTI analyses revealed neither major structural brain abnormalities in the PBC cohort nor correlations with the cognitive and attention performance. Conclusions Despite the high burden of fatigue and selected cognitive deficits, the attention performance of PBC patients appears to be comparable to healthy people. As structural brain alterations do not seem to be present in PBC patients with fatigue, fatigue in PBC must be regarded as purely functional. Future studies should evaluate, whether functional brain changes underlie fatigue in PBC.

Background: Hyper- as well hypothyroidism have an effect on behavior and brain function. Moreover, during development thyroid hormones influence brain structure. Objectives: This study aimed to demonstrate an effect of experimentally induced hyperthyroidism on brain gray matter in healthy adult humans. Methods: High-resolution 3D T1-weighted images were acquired in 29 healthy young subjects prior to as well as after receiving 250 µg of T4 per day for 8 weeks. Voxel-based morphometry analysis was performed using Statistical Parametric Mapping 8 (SPM8). Results: Laboratory testing confirmed the induction of hyperthyroidism. In the hyperthyroid condition, gray matter volumes were increased in the right posterior cerebellum (lobule VI) and decreased in the bilateral visual cortex and anterior cerebellum (lobules I-IV) compared to the euthyroid condition. Conclusions: Our study provides evidence that short periods of hyperthyroidism induce distinct alterations in brain structures of cerebellar regions that have been associated with sensorimotor functions as well as working memory in the literature.

Focal brain lesions may induce dysfunctions in distant brain regions leading to behavioral impairments. Based on this concept of 'diaschisis', spatial neglect following stroke has been related to structural damage of the right-lateralized ventral attention network (VAN) and disrupted inter-hemispheric functional connectivity (FC) in the bilateral dorsal attention network (DAN). We questioned whether neglect-related behavioral deficits may be determined by local dysfunction of a specific region within these brain networks. We investigated acute right-hemisphere stroke patients with left hemispatial neglect using resting-state functional MRI, neuropsychological tests of spatial attention and clinical assessment of neglect-related functional disability. In addition to conventional FC analyses between different cortical regions of interest (ROIs) in the DAN/VAN, we extracted the fractional amplitude of low frequency fluctuations (fALFF) from each ROI as a marker of regional spontaneous neuronal activity. Although DAN regions (as opposed to the VAN regions) were largely spared from structural brain damage, they exhibited a significant reduction of inter-hemispheric FC. However, significant fMRI-behavior correlations were revealed specifically for the fALFF of one DAN-ROI in the right superior parietal lobule (SPL): the smaller the fALFF in the right posterior intraparietal sulcus, the more severe the patient's pathological attention bias and neglect-related functional impairment. In line with 'diaschisis', our findings confirm a crucial role of the non-lesioned but dysfunctional right SPL for the emergence of spatial neglect and its behavioral consequences. They further support targeting the SPL dysfunction by non-invasive brain stimulation in neglect rehabilitation.

Obsessive-compulsive disorder (OCD) is characterized by recurrent intrusive thoughts and ritualized, repetitive behaviors, or mental acts. Convergent experimental evidence from neuroimaging and neuropsychological studies supports an orbitofronto-striato-thalamo-cortical dysfunction in OCD. Moreover, an over excitability of the amygdala and over monitoring of thoughts and actions involving the anterior cingulate, frontal and parietal cortex has been proposed as aspects of pathophysiology in OCD. We chose a data driven, graph theoretical approach to investigate brain network organization in 17 unmedicated OCD patients and 19 controls using resting-state fMRI. OCD patients showed a decreased connectivity of the limbic network to several other brain networks: the basal ganglia network, the default mode network, and the executive/attention network. The connectivity within the limbic network was also found to be decreased in OCD patients compared to healthy controls. Furthermore, we found a stronger connectivity of brain regions within the executive/attention network in OCD patients. This effect was positively correlated with disease severity. The decreased connectivity of limbic regions (amygdala, hippocampus) may be related to several neurocognitive deficits observed in OCD patients involving implicit learning, emotion processing and expectation, and processing of reward and punishment. Limbic disconnection from fronto-parietal regions relevant for (re)-appraisal may explain why intrusive thoughts become and/or remain threatening to patients but not to healthy subjects. Hyperconnectivity within the executive/attention network might be related to OCD symptoms such as excessive monitoring of thoughts and behavior as a dysfunctional strategy to cope with threat and uncertainty.

Hypo- and hyperthyroidism have effects on brain structure and function, as well as cognitive processes, including memory. However, little is known about the influence of thyroid hormones on brain perfusion and the relationship of such perfusion changes with cognition. The present study aimed to demonstrate the effect of short-term experimental hyperthyroidism on brain perfusion in healthy volunteers and to assess whether perfusion changes, if present, are related to cognitive performance. It is known that an interaction exists between brain perfusion and cerebral oxygen consumption rate and it is considered that neural activation increases cerebral regional perfusion rate in brain areas associated with memory. Measuring cerebral blood flow may therefore represent a proxy for neural activity. Therefore, arterial spin labelling (ASL) measurements were conducted and later analysed to evaluate brain perfusion in 29 healthy men before and after ingesting thyroid hormones for 8 weeks. Psychological tests concerning memory were performed at the same time-points and the results were correlated with the imaging results. In the hyperthyroid condition, perfusion was increased in the posterior cerebellum in regions connected with cerebral networks associated with cognitive control and the visual cortex compared to the euthyroid condition. In addition, these perfusion changes were positively correlated with changes of performance in the German version of the Auditory Verbal Learning Task [AVLT, Verbaler Lern-und-Merkfähigkeits-Test (VLMT)]. Cerebellar perfusion and function therefore appears to be modulated by thyroid hormones, likely because the cerebellum hosts a high number of thyroid hormone receptors.

The goal of this project is to develop a multi-channel TOF-PET system with a 300 ps FWHM time resolution, a factor two improvement with respect to commercially available systems (Surti et al., 2007 [1] ). In a TOF-PET system, the time-of-flight information can be used to improve significantly the sensitivity of the detector as shown in Karp et al. (2008) [2] . The target time resolution has been achieved in two channel systems with LYSO (Kim and Wang, 2008 [3] ), the aim is to port this results into a multi-channel system. This work extends the results shown in Gottlich et al. (2010) [4] , studying the stability of the detector performance in different geometries and configurations.

Aims Disturbed levels of thyroid hormones are associated with neuropsychiatric disorders, including memory impairments. The aim of this study was to evaluate effects of mild induced thyrotoxicosis on working memory and its neural correlates. Methods Twenty-nine healthy, male subjects with normal thyroid state participated in the study. Functional MRI was acquired during a working memory task (n-back task) before and after ingesting 250 μg L-thyroxin per day for a period of eight weeks. In addition, neuropsychological tests were performed. Results In the hyperthyroid condition the subjects showed slower reaction times, but a higher accuracy in the 0-back version of the memory tasks. Fewer differences between euthyroid and hyperthyroid state were seen for the more difficult conditions of the n-back task. FMRI revealed effects of difficulty in the parahippocampal gyrus, supplementary motor area, prefrontal cortex, anterior cingulate cortex, posterior cerebellum, rolandic operculum and insula (p

Bilateral vestibular failure (BVF) is a severe chronic disorder of the labyrinth or the eighth cranial nerve characterized by unsteadiness of gait and disabling oscillopsia during head movements. According to animal data, vestibular input to the hippocampus is proposed to contribute to spatial memory and spatial navigation. Except for one seminal study showing the association of impaired spatial navigation and hippocampal atrophy, patient data in BVF are lacking. Therefore, we performed a voxel‐wise comparison of the hippocampal gray matter volume (GMV) in a clinically representative sample of 27 patients with incomplete BVF and 29 age‐ and gender‐matched healthy controls to test the hypothesis of hippocampal atrophy in BVF. Although the two groups did not generally differ in their hippocampal GMV, a reduction of GMV in the bilateral hippocampal CA3 region was significantly correlated with increased vestibulopathy‐related clinical impairment. We propose that GMV reduction in the hippocampus of BVF patients is related to the severity of vestibular‐induced disability which is in line with combined hippocampal atrophy and disorders of spatial navigation in complete vestibular deafferentation due to bilateral nerve section. Clinically, however, the most frequent etiologies of BVF cause incomplete lesions. Accordingly, hippocampus atrophy and deficits in spatial navigation occur possibly less frequently than previously suspected. Hum Brain Mapp 37:1998–2006, 2016. © 2016 Wiley Periodicals, Inc.

Adult onset hyperthyroidism may impact on different cognitive domains, including attention and concentration, memory, perceptual function, language and executive function. Previous PET studies implicated changed functionality of limbic regions, the temporal and frontal lobes in hyperthyroidism, whereas it is unknown whether cognitive effects of hyperthyroidism may be due to changed brain connectivity. This study aimed to investigate the effect of experimentally induced short-term hyperthyroidism thyrotoxicosis on resting-state functional connectivity using functional magnetic resonance imaging. Twenty-nine healthy male right-handed subjects were examined twice, once prior and once after 8 weeks of oral administration of 250 μg levothyroxine per day. Resting-state fMRI was subjected to graph-theory based analysis methods to investigate whole-brain intrinsic functional connectivity. Despite a lack of subjective changes noticed by the subjects significant thyrotoxicosis was confirmed in all subjects. This induced a significant increase in resting-state functional connectivity specifically in the rostral temporal lobes (0.05 FDR corrected at the cluster level), which is caused by an increased connectivity to the cognitive control network. The increased connectivity between temporal poles and the cognitive control network shown here under experimental conditions supports an important function of thyroid hormones in the regulation of paralimbic structures.

Altered neural processing of social signals such as angry facial expressions has been associated with increased aggressive behavior, but evidence for this relationship in healthy persons using ecologically valid experimental designs is lacking. We presented socially relevant videos of facial expressions in a functional magnetic resonance imaging (fMRI) version of the well-established Taylor Aggression Paradigm and investigated 41 healthy male participants, of whom 32 were included in the analysis. In each round of this competitive reaction time task, participants observed their opponent while he selected a punishment level for him, bearing either a neutral or angry facial expression. Afterward, participants in turn selected a punishment level for their opponent. Across participants, reactivity of the medial orbitofrontal cortex (OFC) to angry facial expressions was negatively related to aggressive behavior. Within participants and across trials, activity in the anterior cingulate cortex (ACC) was positively related to aggressive behavior specifically in response to angry expressions. Moreover, we found an effect of angry expressions on neural activity patterns during later stages of the task, demonstrating that the effect of angry expressions on neural reactivity is more than just a short-lived, stimulus-driven response. Our results underscore the importance of OFC and ACC for the shaping of socially adaptive responses to provocation.

We present the first commissioning data of our TOF-PET test device featuring MPPC read-out of small size LFS crystals. We discuss the characteristics of the test device and present results from two different multi-channel read-out ASIC chips which offer a high timing performance.

The Multi-Pixel Photon Counter (MPPC) is a silicon based photon counting device consisting of multiple Avalanche Photodiodes operated in Geiger mode. In order to detect 511 keV photons we use MPPC devices with an active area of 3×3 mm2 which are directly coupled to 3 × 3 × 15 mm3 scintillator crystals made of Lutetium Fine Silicate (LFS). Two gammadetectors of this kind are used to detect both coincident photons emerging from an e+e− annihilation. The energy and the time resolution are measured. The very good performance of the gamma-detectors motivate the next step towards building a gamma camera consisting of a matrix of MPPC devices and scintillator crystals. First results concerning the design and the homogeneity of the read-out channels are presented. About 100 LFS crystals are tested. First studies on the properties of the ASIC which will be used for the multi-channel read-out are discussed. The experimental studies are supplemented with Monte Carlo simulations based on GEANT4. A full PET system is simulated in order to study and optimize the performance of the system in terms of spatial resolution.

Various samples of newly produced Micro-Pixels Photon Counters have been characterized and their properties are compared. The samples differ in the total number of active pixels as well as in the total detector area. The application of these devices for the next generation of highly granular calorimeter readout is discussed. Their enhanced blue sensitivity allows to consider direct coupling to plastic scintillator tiles as an alternative to the traditional readout mediated by a wavelength shifter fiber. The spin-off application for time resolution PET readout is considered. First measurements are presented of energy and time resolution obtained with a test system consisting of two inorganic scintillator crystals coupled to MPPC readout.