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Introduction: We investigated the prosodic perception of uncertainty cues in adults with Autism Spectrum Disorder (ASD) compared to neurotypical adults (NTC). Method: We used articulatory synthetic speech to express uncertainty in a human-machine scenario by varying the three acoustic cues pause, intonation, and hesitation. Twenty-eight adults with ASD and 28 NTC adults rated each answer for uncertainty, naturalness, and comprehensibility. Results: Both groups reliably perceived different levels of uncertainty. Stimuli were rated as less uncertain by the ASD group, but not significantly. Only when we pooled the recipients' ratings for all three cues, did we find a significant group difference. In terms of reaction time, we observed longer reaction times in the ASD group compared to the neurotypical comparison group for the uncertainty level hesitation & strong intonation, but the differences were not significant after Bonferroni correction. Furthermore, our results showed a significant group difference between the correlation of uncertainty and naturalness, i.e. the correlation in the ASD group is significantly lower than in the NTC group. Obtained effect size estimates can inform sample size calculations in future studies for the reliable identification of group differences. Discussion: In future work, we would like to further investigate the interaction of all three cues and uncertainty perception. It would be interesting to further vary the duration of the pause and also to use different types of fillers. From a developmental perspective, uncertainty perception should also be investigated in children and adolescents with ASD. [ABSTRACT FROM AUTHOR]

Introduction Attention-deficit/hyperactivity disorder (ADHD) is a neuro-developmental disorder characterized by early childhood onset and persistent symptoms of attention deficit, motor hyperactivity and impulsivity causing psychosocial impairments in different areas of [...], Background: Based on animal research several authors have warned that the application of methylphenidate, the firstline drug for the treatment of attention-deficit/hyperactivity disorder (ADHD), might have neurotoxic effects potentially harming the brain. We investigated whether methylphenidate application, over a 1-year period, results in cerebral volume decrease. Methods: We acquired structural MRIs in a double-blind study comparing methylphenidate to placebo. Global and regional brain volumes were analyzed at baseline, after 3 months and after 12 months using diffeomorphic anatomic registration through exponentiated lie algebra. Results: We included 131 adult patients with ADHD into the baseline sample, 98 into the 3-month sample (54 in the methylphenidate cohort and 44 in the placebo cohort) and 76 into the 1-year sample (37 in the methylphenidate cohort and 29 in the placebo cohort). Methylphenidate intake compared with placebo did not lead to any detectable cerebral volume loss; there was a trend toward bilateral cerebellar grey matter increase. Limitations: Detecting possible neurotoxic effects of methylphenidate might require a longer observation period. Conclusion: There is no evidence of grey matter volume loss after 1 year of methylphenidate treatment in adult patients with ADHD.

Background: Autoimmune encephalitis (AE) might be seropositive or seronegative, depending on whether antibodies targeting well-characterized neuronal antigens can be detected or not. Since data on treatment efficacy in seronegative cases, are scarce, the main rationale of this study was to evaluate immunotherapy response in seronegative AE in comparison to seropositive cases. Methods: An electronic database search retrospectively identified 150 AE patients, treated in our tertiary care university hospital between 2010 and 2020 with an AE. Therapy response was measured using both general impression and the modified Rankin Scale (mRS). Results: Seventy-four AE patients (49.3%) were seronegative and 76 (50.7%) seropositive. These cases were followed up for a mean of 15.3 (standard deviation, SD, 24.9) and 24.3 months (SD 28.1), respectively. Both groups were largely similar on the basis of numerous clinical and paraclinical findings including cerebrospinal fluid, electroencephalography, magnetic resonance imaging, and 18-F-fluor-desoxy-glucose-positron-emmission-tomography pathologies. The majority of patients (80.4%) received at least one immunotherapy, which were glucocorticoids in most cases (76.4%). Therapy response on general impression was high with 49 (92.5%) of treated seronegative, and 57 (86.4%) of treated seropositive AE cases showing improvement following immunotherapies and not significantly different between both groups. Notably, the proportion of patients with a favorable neurological deficit (mRS 0-2) was twice as high during long-term follow-up as compared to baseline in both groups. Conclusion: Since both, patients with seronegative and seropositive AE, substantially benefitted from immunotherapies, these should be considered in AE patients irrespective of their antibody results. [ABSTRACT FROM AUTHOR]

Introduction: During observation of the ambiguous Necker cube, our perception suddenly reverses between two about equally possible 3D interpretations. During passive observation, perceptual reversals seem to be sudden and spontaneous. A number of theoretical approaches postulate destabilization of neural representations as a pre-condition for reversals of ambiguous figures. In the current study, we focused on possible Electroencephalogram (EEG) correlates of perceptual destabilization, that may allow prediction of an upcoming perceptual reversal. Methods: We presented ambiguous Necker cube stimuli in an onset-paradigm and investigated the neural processes underlying endogenous reversals as compared to perceptual stability across two consecutive stimulus presentations. In a separate experimental condition, disambiguated cube variants were alternated randomly, to exogenously induce perceptual reversals. We compared the EEG immediately before and during endogenous Necker cube reversals with corresponding time windows during exogenously induced perceptual reversals of disambiguated cube variants. Results: For the ambiguous Necker cube stimuli, we found the earliest differences in the EEG between reversal trials and stability trials already 1 s before a reversal occurred, at bilateral parietal electrodes. The traces remained similar until approximately 1100 ms before a perceived reversal, became maximally different at around 890 ms (p = 7.59 × 10-6, Cohen’s d = 1.35) and remained different until shortly before offset of the stimulus preceding the reversal. No such patterns were found in the case of disambiguated cube variants. Discussion: The identified EEG effects may reflect destabilized states of neural representations, related to destabilized perceptual states preceding a perceptual reversal. They further indicate that spontaneous Necker cube reversals are most probably not as spontaneous as generally thought. Rather, the destabilization may occur over a longer time scale, at least 1 s before a reversal event, despite the reversal event as such being perceived as spontaneous by the viewer. [ABSTRACT FROM AUTHOR]

Magneto- and electroencephalography (M/EEG) are widespread techniques to measure neural activity in-vivo at a high temporal resolution but low spatial resolution. Locating the neural sources underlying the M/EEG poses an inverse problem, which is ill-posed. We developed a new method based on Recursive Application of Multiple Signal Classification (MUSIC). Our proposedmethod is able to recover not only the locations but, in contrast to other inverse solutions, also the extent of active brain regions flexibly (FLEX-MUSIC). This is achieved by allowing it to search not only for single dipoles but also dipole clusters of increasing extent to find the best fit during each recursion. FLEX-MUSIC achieved the highest accuracy for both single dipole and extended sources compared to all othermethods tested. Remarkably, FLEX-MUSIC was capable to accurately estimate the level of sparsity in the source space (r = 0.82), whereas all other approaches tested failed to do so (r = 0.18). The average computation time of FLEX-MUSIC was considerably lower compared to a popular Bayesian approach and comparable to that of another recursiveMUSIC approach and eLORETA. FLEX-MUSIC produces only few errors and was capable to reliably estimate the extent of sources. The accuracy and low computation time of FLEX-MUSIC renders it an improved technique to solve M/EEG inverse problems both in neuroscience research and potentially in pre-surgery diagnostic in epilepsy. [ABSTRACT FROM AUTHOR]

Introduction Impulsivity and emotion regulation problems are core traits of borderline personality disorder (BPD) and are related to other symptoms and problematic behaviours. (1) With respect to emotion dysregulation, BPD [...], Background: Both emotion regulation and impulsivity are core aspects of borderline personality disorder (BPD) pathology. Although both problems may be combined specifically in BPD, few studies to date have investigated the emotional modulation of impulsivity in BPD. Methods: Women with BPD and matched healthy controls performed go/no-go tasks after induction of anger, joy or a neutral mood by vocally presented short stories. Dependent variables were the behavioural results and functional magnetic resonance imaging data. Results: We included 17 women with BPD and 18 controls in our study. No behavioural group differences were found. However, patients with BPD showed stronger activation of the left amygdala and weaker activation of the subgenual anterior cingulate during anger induction than controls. Inhibition in the go/no-go task after anger induction increased activity in the left inferior frontal cortex in controls, but not in women with BPD, who, in turn, showed increased activation in the subthalamic nucleus. Limitations: Findings cannot be generalized to men, and 4 patients were taking antidepressant medication (selective serotonin reuptake inhibitors). In addition, no patient control group was investigated, thus we do not know whether findings are specific to BPD compared with other disorders. Conclusion: Our findings are consistent with the view that a disturbed amygdala-prefrontal network in patients with BPD is compensated by a subcortical loop involving the subthalamic nucleus, leading to normal behavioural inhibition in these patients.

Objective: Attention-deficit hyperactivity disorder (ADHD) in adulthood is a serious health problem with a prevalence of up to 4%. Limbic structures have been implicated in the genesis of ADHD; it [...]

Objective: Decreased brain volumes in prefrontal, limbic and parietal areas have been found in women with borderline personality disorder (BPD). Recent models suggest impaired structural and functional connectivity in this [...]

Autoimmune obsessive-compulsive disorder (OCD) is rare. The case presented here is that of a female patient in her mid-thirties who developed postpartum OCD. Magnetic resonance imaging showed multiple juxtacortical hyperintensities that may have been post-inflammatory in origin. In tissuebased assays using mouse brain slices, the patient's cerebrospinal fluid (CSF) showed novel anti-nucleoli autoantibodies in cerebellar Purkinje cells and cortical neurons. The CSF dopamine and glutamate concentrations were dysregulated. The clinical course and diagnostic findings were compatible with possible autoimmune OCD with postpartum onset. [ABSTRACT FROM AUTHOR]

Sensory features in autism spectrum disorder (ASD) have received increasing interest in clinical work and research during the recent years. With the Sensory Perception Quotient (SPQ), Tavasolli and colleagues have produced a self-rating scale for adults with ASD that measures sensory hyper-sensitivity in different sensory modalities, without also tapping cognitive or motivational aspects that precede or follow autistic sensory experiences. Here, we present the results of a translation of the SPQ to German and its short version as well as their validation in samples of autistic or neuro-typical participants. We, furthermore, present the psychometric properties and validities of Tavasolli's original SPQ-short version as well as an alternative short version based on different psychometric item-selection criteria. We can show here that our alternative SPQ-short version, overlapping with the original short-version in 61% of its items, exhibits superior reliabilities, reasonable concurrent validities with other related measures. It, furthermore, exhibits excellent differentiation between autistic and non-autistic samples, underscoring its utility as a screening instrument in research and a clinical instrument to supplement the ASD diagnostic process. [ABSTRACT FROM AUTHOR]

Introduction: Reelin (RELN) is an extracellular glycoprotein best known to be crucial for neuronal migration during the embryonic period and regulation of synaptic plasticity in the adult brain, with recent studies pointing to reelin playing an important part in the organization of peripheral organs as well. Abnormalities in RELN function are associated with a variety of medical conditions in human beings. These alterations partly also reflect in RELN's blood levels, which gives it a clinical relevance as a potential biomarker. Requirement for a possible clinical use is a profound understanding of RELN's physiology. We hypothesized blood RELN levels could underlie time-dependent variations and therefore examined individuals' serum reelin concentrations in the course of one day.Material and Methods: We obtained blood samples from healthy individuals (n = 10) at several times of measurement over a time period of 24 h. We subsequently determined the respective serum RELN concentrations utilizing an enzyme-linked immunosorbent assay and tested for intra- and interindividual variations in serum RELN concentrations over time.Results: All tested individuals' serum RELN levels displayed significant intraindividual variations in the course of 24 h. Test subjects' reelin day profiles showed substantial divergence among each other.Conclusions: Our findings point to short-term fluctuations in blood RELN levels being part of physiological RELN homeostasis. This is of special interest with regard to a potential clinical use of RELN as a biomarker. [ABSTRACT FROM AUTHOR]

Background: We previously described inflammatory cerebrospinal fluid (CSF) alterations in a subgroup of patients with schizophreniform disorders and the synthesis of polyspecific intrathecal antibodies against different neurotropic infectious pathogens in some patients with bipolar disorders. Consequently, we have measured the prevalence of a positive MRZ reaction (MRZR)--a marker for a polyspecific, antiviral, intrathecal, humoral immune response composed of three antibody indices for the neurotropic viruses of measles (M), rubella (R), and varicella zoster (Z)--in these patients. Methods: We analyzed paired CSF and serum samples of 39 schizophreniform and 39 bipolar patients. For comparison, we used a group of 48 patients with other inflammatory neurological disorders (OIND) and a cohort of 203 multiple sclerosis (MS) patients. Results: We found a positive MRZR in two patients with schizophreniform disorders (5.1%); both suffered from schizodepressive disorders without any other signs suggestive of MS. None of the bipolar patients (0%) and four members of the OIND group (8.3%) showed a positive MRZR. In the MS cohort, a positive MRZR was found significantly more frequently [in 99 patients (48.8%)] than in the other patient groups (p > 0.001). In summary, we did not find a positive MRZR in a relevant subgroup of patients with schizophreniform or bipolar disorders. Conclusions: Our results indicate that the MRZR is highly specific to MS. Nevertheless, two schizodepressive patients also had a positive MRZR. This finding corresponds to the few MRZR-positive patients with OIND or other autoimmune disorders with central nervous involvement, implicating that the MRZR specificity for MS is high, but not 100%. [ABSTRACT FROM AUTHOR]

Background: Hashimoto's encephalopathy (HE) is a rare immunological neuropsychiatric disorder characterized by increased antithyroid antibodies and mixed neurological and psychiatric symptoms. HE has been previously discussed as a differential diagnosis for rapid progressive dementia. However, most of these patients suffered from additional neurological symptoms, like ataxia or seizures. Case presentation: Here, we present the case of a 59-year-old female patient suffering rapid onset dementia with salient frontal executive dysfunction. She developed rapid onset symptoms, including apathy, verbal depletion up to a stuporous state, severe working memory deficits, evidence of primitive reflexes, disturbed Luria's three-step test, and micturition disorder. Analysis of her cerebrospinal fluid was normal. The serum analyses showed increased antithyroid (antithyroid peroxidase and antithyroglobulin) antibodies. In the cerebral magnetic resonance imaging, supratentorial deep and peripheral white matter lesions were found; the electroencephalography showed intermittent slowing, and the [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) depicted medial and superior dorsolateral frontal hypometabolism. Several different psychopharmacological therapeutic approaches with various neuroleptics, antidepressants, and high doses of lorazepam were unsuccessful. Due to the organic alterations, including increased antithyroid antibodies, HE was suspected. Against expectations, treatment with high-dose corticosteroids proved to be ineffective and was associated with worsening symptoms. However, escalated treatment with plasmapheresis over 5 days led to significant improvement in all reported symptoms and in psychometric testing. The neuropsychological improvement was stable over a 6-month follow-up period, and the FDG-PET normalized. Conclusion: This case report reveals that (1) HE can mimic rapid onset dementia with predominantly frontal dysfunction; (2) this syndrome can be successfully treated in the context of HE; and (3) plasmapheresis can be effective in such a disease constellation. The detection of the immunological causes of rapid onset dementia and other psychiatric syndromes is important because it opens opportunities for new, innovative immunosuppressive treatment options. [ABSTRACT FROM AUTHOR]

Background: Schizophreniform syndromes can be divided into primary forms from polygenic causes or secondary forms due to immunological, epileptiform, monogenic, or degenerative causes. Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is a secondary immunological form associated with increased thyroid antibodies, such as antithyroid peroxidase antibodies and shows a good response to corticosteroids. Case presentation: We present the case of a 41-year-old woman suffering from a schizophreniform syndrome. Starting at the age of 35, she developed psychotic exac- erbations with formal thought disorder, acoustic hallucinations, cenesthopathic experi- ences, and loss of ego boundaries. At the same time, she began to suffer from chronic sexual delusions and olfactory hallucinations, which did not respond to neuroleptic med- ication. Her levels of antithyroid peroxidase antibodies were slightly increased, and the blood--brain barrier was disturbed. An electroencephalogram (EEG) showed intermittent generalized slowing, and cerebral magnetic resonance imaging (cMRI) depicted mild tem- porolateral atrophy. High-dose corticosteroid treatment led to convincing improvement of attentional performance and the disappearance of delusions and olfactory hallucinations. Conclusion: SREAT can mimic typical symptoms of schizophreniform syndromes. The increased titer of antithyroid peroxidase antibodies in combination with the EEG slowing, blood--brain barrier dysfunction, and the cMRI alterations were the basis for suspecting an immunological cause in our patient. Chronic delusions, olfactory hallucinations, and cognitive defcits were successfully treated with corticosteroids. The occurrence of sec- ondary immunological forms of schizophreniform syndromes demonstrates the need for innovative immunosuppressive treatment options. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by difficulties in social communication, unusually restricted, repetitive behavior and interests, and specific abnormalities in language and perception. The precise etiology of ASD is still unknown and probably heterogeneous. In a subgroup of patients, toxic environmental exposure might lead to an imbalance between oxidative stress and anti-oxidant systems. Previous serum and postmortem studies measuring levels of glutathione (GSH), the main cellular free radical scavenger in the brain, have supported the hypothesis that this compound might play a role in the pathophysiology of autism. Methods: Using the method of single-voxel proton magnetic resonance spectroscopy (MRS), we analyzed the GSH signal in the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (DLPFC) of 24 ASD patients with normal or above average IQs and 18 matched control subjects. We hypothesized that we would find decreased GSH concentrations in both regions. Results: We did not find overall group differences in neurometabolites including GSH, neither in the dorsal ACC (Wilks' lambda test; p = 0.429) nor in the DLPFC (p = 0.288). In the dACC, we found a trend for decreased GSH signals in ASD patients (p = 0.076). Conclusions: We were unable to confirm our working hypothesis regarding decreased GSH concentrations in the ASD group. Further studies combining MRS, serum, and cerebrospinal fluid measurements of GSH metabolism including other regions of interest or even whole brain spectroscopy are needed. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia-like disorders can be divided into endogenic or primary, idiopathic, polygenetic forms, and different secondary, organic subgroups [e.g., (para)epileptic, immunological, degenerative]. Epileptic and paraepileptic explanatory approaches have a long tradition due to the high rate of electroencephalography (EEG) alterations in patients with schizophrenia. Case presentation: We present the case of a 23-year-old female patient suffering, since the age of 14 years, from a fluctuating paranoid-hallucinatory syndrome with formal thought disorder, fear, delusions of persecution, auditory, visual, and tactile hallucinations, as well as negative and cognitive symptoms. Laboratory measurements showed increased titers of antinuclear antibodies (ANAs) in the context of ulcerative colitis. While there was no clear history or evidence of epileptic seizures, the EEG showed generalized 3 Hz polyspike wave complexes. Under treatment with levetiracetam, the symptoms disappeared and the patient was able to complete vocational training. Conclusion: The schizophrenia-like symptoms associated with epileptiform discharges but not overt seizures and the good response to antiepileptic treatment could be interpreted in the context of a (para)epileptic pathomechanism. The EEG alterations might be due to a polygenetic effect due to different genes. Mild immunological mechanisms in the framework of ulcerative colitis and increased ANA titers might have supported the network instability. This case report illustrates (1) the importance of EEG screenings in schizophrenia, (2) a potential pathogenetic role of epileptiform discharges in a subgroup of patients with schizophrenia-like symptoms, and (3) that antiepileptic medication with levetiracetam could be a successful treatment alternative in schizophrenia-like disorders with EEG alterations. [ABSTRACT FROM AUTHOR]

Neuroscience is a multidisciplinary effort to understand the structures and functions of the brain and brain-mind relations. This effort results in an increasing amount of data, generated by sophisticated technologies. However, these data enhance our descriptive knowledge, rather than improve our understanding of brain functions. This is caused by methodological gaps both within and between subdisciplines constituting neuroscience, and the atomistic approach that limits the study of macroand mesoscopic issues. Whole-brain measurement technologies do not resolve these issues, but rather aggravate them by the complexity problem. The present article is devoted to methodological and epistemic problems that obstruct the development of human neuroscience. We neither discuss ontological questions (e.g., the nature of the mind) nor review data, except when it is necessary to demonstrate a methodological issue. As regards intradisciplinary methodological problems, we concentrate on those within neurobiology (e.g., the gap between electrical and chemical approaches to neurophysiological processes) and psychology (missing theoretical concepts). As regards interdisciplinary problems, we suggest that core disciplines of neuroscience can be integrated using systemic concepts that also entail human-environment relations.We emphasize the necessity of a meta-discussion that should entail a closer cooperation with philosophy as a discipline of systematic reflection. The atomistic reduction should be complemented by the explicit consideration of the embodiedness of the brain and the embeddedness of humans. The discussion is aimed at the development of an explicit methodology of integrative human neuroscience, which will not only link different fields and levels, but also help in understanding clinical phenomena. [ABSTRACT FROM AUTHOR]

In neuropsychiatric research, the aspects of sex have received increasing attention over the past decade. With regard to the neurometabolic differences in the prefrontal cortex and the cerebellum of both men and women, we performed a magnetic resonance spectroscopic (MRS) study of a large group of healthy subjects. For neurometabolic measurements, we used single-voxel proton MRS. The voxels of interest (VOI) were placed in the pregenual anterior cingulate cortex (pACC) and the left cerebellar hemisphere. Absolute quantification of creatine (Cre), total choline (t-Cho), glutamate and glutamine (Glx), N-acetylaspartate, and myo-inositol (mI) was performed. Thirty-three automatically matched ACCs and 31 cerebellar male-female pairs were statistically analyzed. We found no significant neurometabolic differences in the pACC region (Wilks' lambda: p = 0.657). In the left cerebellar region, we detected significant variations between the male and female groups (p = 0.001). Specifically, we detected significantly higher Cre (p = 0.005) and t-Cho (p = 0.000) levels in men. Additionally, males tended to have higher Glx and mI concentrations. This is the first study to report neurometabolic sex differences in the cerebellum. The effects of sexual hormones might have influenced our findings. Our data indicates the importance of adjusting for the confounding effects of sex in MRS studies. [ABSTRACT FROM AUTHOR]

Background: Hashimoto's encephalopathy is a neuropsychiatric disease with symptoms of cognitive impairment, stroke-like episodes, seizures, and psychotic or affective symptoms associated with autoimmune thyroiditis and excellent steroid responsiveness; therefore, it is also called "steroid responsive encephalopathy associated with autoimmune thyroiditis" (SREAT). Case presentation: We present the case of a 50-year-old woman who developed a first-onset depressive syndrome with predominant cognitive impairment and inability to work. Antidepressive treatment and cognitive behavioral therapy over two years were unsuccessful. Neurological examination was unremarkable. Serum analysis showed increased thyroid peroxidase and thyroglobulin antibodies. Cerebrospinal fluid protein and albumin quotient were increased. Magnetic resonance imaging depicted unspecific, supratentorial white matter lesions and frontal accentuated brain atrophy. Electroencephalography was normal. Neuropsychological testing for attentional performance was below average. High-dose intravenous treatment with methylprednisolone over 5 days and oral dose reduction over 3 weeks led to the sustained improvement of clinical symptoms. Following discharge from the hospital, the patient returned to work, and 6.5 months after the start of therapy, no neuropsychological deficit remained. Conclusion: This case report illustrates that SREAT might present with purely depressive symptoms, thus mimicking classical major depression. In such cases, corticosteroid therapy may be an effective treatment option. [ABSTRACT FROM AUTHOR]