Thomas F. Münte

ISLES 2015 - A public evaluation benchmark for ischemic stroke lesion segmentation from multispectral MRI

&NA; Ischemic stroke is the most common cerebrovascular disease, and its diagnosis, treatment, and study relies on non‐invasive imaging. Algorithms for stroke lesion segmentation from magnetic resonance imaging (MRI) volumes are intensely researched, but the reported results are largely incomparable due to different datasets and evaluation schemes. We approached this urgent problem of comparability with the Ischemic Stroke Lesion Segmentation (ISLES) challenge organized in conjunction with the MICCAI 2015 conference. In this paper we propose a common evaluation framework, describe the publicly available datasets, and present the results of the two sub‐challenges: Sub‐Acute Stroke Lesion Segmentation (SISS) and Stroke Perfusion Estimation (SPES). A total of 16 research groups participated with a wide range of state‐of‐the‐art automatic segmentation algorithms. A thorough analysis of the obtained data enables a critical evaluation of the current state‐of‐the‐art, recommendations for further developments, and the identification of remaining challenges. The segmentation of acute perfusion lesions addressed in SPES was found to be feasible. However, algorithms applied to sub‐acute lesion segmentation in SISS still lack accuracy. Overall, no algorithmic characteristic of any method was found to perform superior to the others. Instead, the characteristics of stroke lesion appearances, their evolution, and the observed challenges should be studied in detail. The annotated ISLES image datasets continue to be publicly available through an online evaluation system to serve as an ongoing benchmarking resource (www.isles‐challenge.org). HighlightsEvaluation framework for automatic stroke lesion segmentation from MRIPublic multi‐center, multi‐vendor, multi‐protocol databases releasedOngoing fair and automated benchmark with expert created ground truth setsComparison of 14+7 groups who responded to an open challenge in MICCAISegmentation feasible in acute and unsolved in sub‐acute cases Graphical abstract Figure. No caption available.

Evaluation of Cognitive Deficits and Structural Hippocampal Damage in Encephalitis With Leucine-Rich, Glioma-Inactivated 1 Antibodies.

Importance Limbic encephalitis with leucine-rich, glioma-inactivated 1 (LGI1) antibodies is one of the most frequent variants of autoimmune encephalitis with antibodies targeting neuronal surface antigens. However, the neuroimaging pattern and long-term cognitive outcome are not well understood. Objective To study cognitive outcome and structural magnetic resonance imaging (MRI) alterations in patients with anti-LGI1 encephalitis. Design, Setting, and Participants A cross-sectional study was conducted at the Departments of Neurology at Charité-Universitätsmedizin Berlin and University Hospital Schleswig-Holstein, Kiel, Germany. Data on 30 patients with anti-LGI1 encephalitis and 27 healthy control individuals matched for age, sex, and educational level were collected from June 1, 2013, through February 28, 2015. Main Outcomes and Measures Clinical assessment, cognitive testing, and high-resolution MRI data, including whole-brain, hippocampal and basal ganglia volumetry; white matter integrity (diffusion tensor imaging); gray matter density (voxel-based morphometry); and hippocampal microstructural integrity (mean diffusivity and fractional anisotropy). Results Of the 30 patients included in the study, 19 were male (63%); mean (SD) age was 65.7 (12.3) years. Patients with anti-LGI1 encephalitis had incomplete recovery with significant and persisting verbal (mean [SE] Rey Auditory Verbal Learning Test [RAVLT], delayed recall: patients, 6.52 [1.05]; controls, 11.78 [0.56], Pu2009<u2009.001) and visuospatial (Rey-Osterrieth Complex Figure Test [ROCF], delayed recall: patients, 16.0 [1.96]; controls, 25.86 [1.24]; Pu2009<u2009.001) memory deficits. These deficits were accompanied by pronounced hippocampal atrophy, including subfields cornu ammonis 2/3 (CA2/3) and CA4/dentate gyrus (DG), as well as impaired hippocampal microstructural integrity. Higher disease severity correlated with larger verbal memory deficits (RAVLT delayed recall, ru2009=u2009−0.40; Pu2009=u2009.049), decreased volumes of left hippocampus (ru2009=u2009−0.47; Pu2009=u2009.02) and left CA2/3 (ru2009=u2009−0.41; Pu2009=u2009.04) and CA4/DG (ru2009=u2009−0.43; Pu2009=u2009.03) subfields, and impaired left hippocampal microstructural integrity (ru2009=u20090.47; Pu2009=u2009.01). In turn, decreased volume of the left CA2/3 subfield (RAVLT delayed recall, ru2009=u20090.40; Pu2009=u2009.047) and impaired left hippocampal microstructural integrity (RAVLT recognition, ru2009=u2009−0.41; Pu2009=u2009.04) correlated with verbal memory deficits. Basal ganglia MRI signal abnormalities were observed in only 1 patient, but a longer duration of faciobrachial dystonic seizures correlated with a reduction of pallidum volume (ru2009=u2009−0.71; Pu2009=u2009.03). In contrast, no abnormalities of cortical gray matter or white matter were found. The latency between disease onset and initiation of immunotherapy was significantly correlated with verbal (RAVLT recall after interference, ru2009=u2009−0.48; Pu2009=u2009.02) and visuospatial (ROCF delayed recall, ru2009=u2009−0.46; Pu2009=u2009.03) memory deficits. Conclusions and Relevance Anti-LGI1 encephalitis is associated with cognitive deficits and disability as a result of structural damage to the hippocampal memory system. This damage might be prevented by early immunotherapy.

Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model

BackgroundDeterminations of thyrotropin (TSH) and free thyroxine (FT4) represent the gold standard in evaluation of thyroid function. To screen for novel peripheral biomarkers of thyroid function and to characterize FT4-associated physiological signatures in human plasma we used an untargeted OMICS approach in a thyrotoxicosis model.MethodsA sample of 16 healthy young men were treated with levothyroxine for 8xa0weeks and plasma was sampled before the intake was started as well as at two points during treatment and after its completion, respectively. Mass spectrometry-derived metabolite and protein levels were related to FT4 serum concentrations using mixed-effect linear regression models in a robust setting. To compile a molecular signature discriminating between thyrotoxicosis and euthyroidism, a random forest was trained and validated in a two-stage cross-validation procedure.ResultsDespite the absence of obvious clinical symptoms, mass spectrometry analyses detected 65 metabolites and 63 proteins exhibiting significant associations with serum FT4. A subset of 15 molecules allowed a robust and good prediction of thyroid hormone function (AUCu2009=u20090.86) without prior information on TSH or FT4. Main FT4-associated signatures indicated increased resting energy expenditure, augmented defense against systemic oxidative stress, decreased lipoprotein particle levels, and increased levels of complement system proteins and coagulation factors. Further association findings question the reliability of kidney function assessment under hyperthyroid conditions and suggest a link between hyperthyroidism and cardiovascular diseases via increased dimethylarginine levels.ConclusionOur results emphasize the power of untargeted OMICs approaches to detect novel pathways of thyroid hormone action. Furthermore, beyond TSH and FT4, we demonstrated the potential of such analyses to identify new molecular signatures for diagnosis and treatment of thyroid disorders. This study was registered at the German Clinical Trials Register (DRKS) [DRKS00011275] on the 16th of November 2016.

Lack of Evidence That Neural Empathic Responses Are Blunted in Excessive Users of Violent Video Games: An fMRI Study

The use of violent video games has been often linked to increase of aggressive behavior. According to the General Aggression Model, one of the central mechanisms for this aggressiveness inducing impact is an emotional desensitization process resulting from long lasting repeated violent game playing. This desensitization should evidence itself in a lack of empathy. Recent research has focused primarily on acute, short term impact of violent media use but only little is known about long term effects. In this study 15 excessive users of violent games and control subjects matched for age and education viewed pictures depicting emotional and neutral situations with and without social interaction while fMRI activations were obtained. While the typical pattern of activations for empathy and theory of mind networks was seen, both groups showed no differences in brain responses. We interpret our results as evidence against the desensitization hypothesis and suggest that the impact of violent media on emotional processing may be rather acute and short-lived.

Reduced alpha-gamma phase amplitude coupling over right parietal cortex is associated with implicit visuomotor sequence learning

Implicit visuomotor sequence learning is important for our daily life, e.g., when writing or playing an instrument. Previous research identified a network of cortical regions that is relevant for motor sequence learning, namely primary motor cortex, premotor cortex, superior parietal cortex, and subcortical regions, including basal ganglia and cerebellum. Here, we investigated learning-related changes in oscillatory activity (theta, alpha and gamma power) and cross-frequency interactions (theta- and alpha-gamma phase-amplitude coupling) within cortical regions during sensorimotor memory formation. EEG was recorded from a large group of participants (n=73) performing the serial reaction time task (SRTT). Posterior parietal alpha power was larger early-on during sequence learning and smaller in later sessions. Alpha/low-gamma (8-13Hz and 30-48Hz) phase-amplitude coupling (PAC) was significantly smaller during sequence learning over right superior parietal cortex and frontal cortex. During the transition from sequential stimuli to random stimuli, participants made more errors, indicating that they still implicitly attempted to implement the learned motor sequence. At the same time, alpha/low-gamma phase-amplitude coupling was found to be smaller during the transition relative to later random trials. Our results show that learning and implementing a learned motor sequence reduces alpha/low-gamma PAC over parietal and frontal cortex. Fronto-parietal alpha/low-gamma PAC might be relevant for visuomotor mapping which becomes less relevant once the motor sequence has been encoded.

Neuroanatomical changes extend beyond striatal atrophy in X-linked dystonia parkinsonism

BACKGROUNDnX-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative adult-onset basal ganglia model disease associated with severe striatal atrophy. Anatomical changes exceeding striatal pathology were not yet described in XDP. The present study aimed to assess the microstructure of white matter tracts in XDP using magnetic resonance tomography.nnnMETHODSnDiffusion-weighted imaging was done in 10 XDP patients, aged 42.2 years (SD 8.1), and 14 ethnicity and age-matched controls, aged 40.2 years (SD 6.4). Based on diffusion tensor images, mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated.nnnRESULTSnExcept for in the occipital lobe, XDP patients showed generally increased MD values across the entire white matter. FA map analysis identified four significant clusters with controls showing higher FA values than XDP patients. Involved regions included the fornix, anterior thalamic radiation, corticospinal tract, and superior corona radiata bilaterally. In the fornix and the anterior thalamic radiation, the UPDRSIII total score showed a negative correlation with mean FA values at a trend level (tauxa0=xa0-0.40, pxa0=xa00.053). Volumetric analysis revealed significant gray matter volume loss of putamen (F(1,19)xa0=xa044.2, pxa0<xa00.001), caudate nucleus (F(1,19)xa0=xa054.3, pxa0<xa00.001), and pallidum (F(1,19)xa0=xa08.9, pxa0=xa00.007).nnnCONCLUSIONSnThe present study confirms striatal atrophy in XDP and provides evidence for a strong involvement of the white matter and the pallidum. This calls into question the previously held concept of exclusive striatal atrophy in this unique movement disorder. The spared occipital region may point towards a lack of anatomical connections with the atrophied striatum.

Impact of nutrition on social decision making

Significance Food intake is essential for survival in all species for meeting energetic demands. However, food intake also modulates various biochemical processes underlying cognition. Across two studies, we showed that different macronutrient compositions in standard European meals affect plasma neurotransmitter precursor levels, and these in turn influence social decision making. Our results provide evidence that variations in the macronutrient content of a normal European meal exert a significant impact on high-level human cognition. This study opens perspectives on nutrition-driven cognition modulation. The results have implications for education, economics, and public policy by emphasizing the importance of a balanced diet on fundamental expressions of cognition. Food intake is essential for maintaining homeostasis, which is necessary for survival in all species. However, food intake also impacts multiple biochemical processes that influence our behavior. Here, we investigate the causal relationship between macronutrient composition, its bodily biochemical impact, and a modulation of human social decision making. Across two studies, we show that breakfasts with different macronutrient compositions modulated human social behavior. Breakfasts with a high-carbohydrate/protein ratio increased social punishment behavior in response to norm violations compared with that in response to a low carbohydrate/protein meal. We show that these macronutrient-induced behavioral changes in social decision making are causally related to a lowering of plasma tyrosine levels. The findings indicate that, in a limited sense, “we are what we eat” and provide a perspective on a nutrition-driven modulation of cognition. The findings have implications for education, economics, and public policy, and emphasize that the importance of a balanced diet may extend beyond the mere physical benefits of adequate nutrition.

Effect of Mild Thyrotoxicosis on Performance and Brain Activations in a Working Memory Task.

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<0.05, FWE corrected). When comparing euthyroid and hyperthyroid condition in relation to task-induced activation, differences of activation were found in the right prefrontal cortex as well as in the right parahippocampal area. In the psychological assessment, the alerting effect in the Attention Network Task (ANT) and four out of five parameters of the auditory verbal learning test (AVLT) showed an increase from euthyroid to hyperthyroid state. Conclusions It can be concluded that even a short-term intake of thyroid hormones leads to an activation of brain areas associated with working memory and to an improvement of accuracy of working memory tasks.

Neurophysiological evidence of impaired self-monitoring in schizotypal personality disorder and its reversal by dopaminergic antagonism.

Background Schizotypal personality disorder (SPD) is a schizophrenia-spectrum disorder characterized by odd or bizarre behavior, strange speech, magical thinking, unusual perceptual experiences, and social anhedonia. Schizophrenia proper has been associated with anomalies in dopaminergic neurotransmission and deficits in neurophysiological markers of self-monitoring, such as low amplitude in cognitive event-related brain potentials (ERPs) like the error-related negativity (ERN), and the error positivity (Pe). These components occur after performance errors, rely on adequate fronto-striatal function, and are sensitive to dopaminergic modulation. Here we postulated that analogous to observations in schizophrenia, SPD individuals would show deficits in self-monitoring, as measured by the ERN and the Pe. We also assessed the capacity of dopaminergic antagonists to reverse these postulated deficits. Methods We recorded the electroencephalogram (EEG) from 9 SPD individuals and 12 healthy controls in two separate experimental sessions while they performed the Eriksen Flanker Task, a classical task recruiting behavioral monitoring. Participants received a placebo or 1 mg risperidone according to a double-blind randomized design. Results After placebo, SPD individuals showed slower reaction times to hits, longer correction times following errors and reduced ERN and Pe amplitudes. While risperidone impaired performance and decreased ERN and Pe in the control group, it led to behavioral improvements and ERN amplitude increases in the SPD individuals. Conclusions These results indicate that SPD individuals show deficits in self-monitoring analogous to those in schizophrenia. These deficits can be evidenced by neurophysiological measures, suggest a dopaminergic imbalance, and can be reverted by dopaminergic antagonists.

Winning is not enough: ventral striatum connectivity during physical aggression

Social neuroscience studies have shown that the ventral striatum (VS), a highly reward-sensitive brain area, is activated when participants win competitive tasks. However, in these settings winning often entails both avoiding punishment and punishing the opponent. It is thus unclear whether the rewarding properties of winning are mainly associated to punishment avoidance, or if punishing the opponent can be additionally gratifying. In the present paper we explored the neurophysiological correlates of each outcome, aiming to better understand the development of aggression episodes. We previously introduced a competitive reaction time task that separates both effects: in half of the won trials, participants can physically punish their opponent (active trials), whereas in the other half they can only avoid a punishment (passive trials). We performed functional connectivity analysis seeded in the VS to test for differential network interactions in active compared to passive trials. The VS showed greater connectivity with areas involved in reward valuation (orbitofrontal cortex), arousal (dorsal thalamus and posterior insula), attention (inferior occipital gyrus), and motor control (supplementary motor area) in active compared to passive trials, whereas connectivity between the VS and the inferior frontal gyrus decreased. Interindividual variability in connectivity strength between VS and posterior insula was related to aggressive behavior, whereas connectivity between VS and supplementary motor area was related to faster reaction times in active trials. Our results suggest that punishing a provoking opponent when winning might adaptively favor a “competitive state” in the course of an aggressive interaction.