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TRIAL REGISTRATION: German Clinical Trials Register identifier: DRKS00024005.

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Social cognition, in particular mindreading, enables the understanding of another individual's feelings, intentions, desires, and mental states. The Reading the Mind in the Eyes Test (RMET) captures the ability to identify mental states from gaze. We investigated RMET accuracy in the context of age and cognition across the whole adult age-range (19-79 years) in a very large population-based sample (N = 1,603) with linear regression models accounting for cognitive abilities, neurological diseases, and psychiatric disorders. Higher age predicted lower RMET performance in women and men, suggesting difficulties to infer mental states from gaze at older age. Effects remained stable when taking other cognitive abilities and psychiatric disorders or neurological diseases into account. Our results show that RMET performance as a measure of social cognition declines with increasing age.

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Virtual reality (VR) represents a key technology of the 21st century, attracting substantial interest from a wide range of scientific disciplines. With regard to clinical neuropsychology, a multitude of new VR applications are being developed to overcome the limitations of classical paradigms. Consequently, researchers increasingly face the challenge of systematically evaluating the characteristics and quality of VR applications to design the optimal paradigm for their specific research question and study population. However, the multifaceted character of contemporary VR is not adequately captured by the traditional quality criteria (ie, objectivity, reliability, validity), highlighting the need for an extended paradigm evaluation framework. To address this gap, we propose a multidimensional evaluation framework for VR applications in clinical neuropsychology, summarized as an easy-to-use checklist (VR-Check). This framework rests on 10 main evaluation dimensions encompassing cognitive domain specificity, ecological relevance, technical feasibility, user feasibility, user motivation, task adaptability, performance quantification, immersive capacities, training feasibility, and predictable pitfalls. We show how VR-Check enables systematic and comparative paradigm optimization by illustrating its application in an exemplary research project on the assessment of spatial cognition and executive functions with immersive VR. This application furthermore demonstrates how the framework allows researchers to identify across-domain trade-offs, makes deliberate design decisions explicit, and optimizes the allocation of study resources. Complementing recent approaches to standardize clinical VR studies, the VR-Check framework enables systematic and project-specific paradigm optimization for behavioral and cognitive research in neuropsychology.

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The reliable, valid and economic assessment of social cognition is more relevant than ever in the field of clinical psychology. Theory of Mind is one of the most important socio-cognitive abilities but standardized assessment instruments for adults are rare. The Reading the Mind in the Eyes Test (RMET) is well-established and captures the ability to identify mental states from gaze. Here, we computed standard scores for the German version of the RMET derived from a large, community-dwelling sample of healthy adults (20-79 years). The standardization sample contains 966 healthy adult individuals of the population-based Leipzig Research Center for Civilization Diseases (LIFE) study. Before standardization, weighting factors were applied to match the current sample with distribution characteristics of the German population regarding age, sex, and education. RMET scores were translated into percentage ranks for men and women of five age groups (20-29, 30-39, 40-49, 50-59, 60+ years). Age-specific percentage ranks are provided for men and women. Independent of age, men present a larger variance in test scores compared to women. Within the specific age groups, women score higher and their scoring range is less variable. With increasing age, the scoring variance increases in both men and women. This is the first study providing age- and sex-specific RMET standard scores. Data was weighted to match German population characteristics, enabling the application of standard scores across German-speaking areas. Our results contribute to the standardized assessment of socio-cognitive abilities in clinical diagnostics.

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In humans, action errors and perceptual novelty elicit activity in a shared frontostriatal brain network, allowing them to adapt their ongoing behavior to such unexpected action outcomes. Healthy and pathologic aging reduces the integrity of white matter pathways that connect individual hubs of such networks and can impair the associated cognitive functions. Here, we investigated whether structural disconnection within this network because of small-vessel disease impairs the neural processes that subserve motor slowing after errors and novelty (post-error slowing, PES; post-novel slowing, PNS). Participants with intact frontostriatal circuitry showed increased right-lateralized beta-band (12-24 Hz) synchrony between frontocentral and frontolateral electrode sites in the electroencephalogram after errors and novelty, indexing increased neural communication. Importantly, this synchrony correlated with PES and PNS across participants. Furthermore, such synchrony was reduced in participants with frontostriatal white matter damage, in line with reduced PES and PNS. The results demonstrate that behavioral change after errors and novelty result from coordinated neural activity across a frontostriatal brain network and that such cognitive control is impaired by reduced white matter integrity.

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Cerebral small vessel disease, mainly characterized by white matter lesions and lacunes, has a high clinical impact as it leads to vascular dementia. Recent studies have shown that this disease impairs frontoparietal networks. Here, we apply resting-state magnetic resonance imaging and data-driven whole-brain imaging analysis methods (eigenvector centrality) to investigate changes of the functional connectome in early small vessel disease. We show reduced connectivity in frontoparietal networks, whereas connectivity increases in the cerebellum. These functional changes are closely related to white matter lesions and typical neuropsychological deficits associated with small vessel disease.

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The current study investigated neuropsychological and underlying structural and functional brain alterations in long-term adequately treated patients with Hashimoto's thyroiditis in order to examine much discussed residual complaints in patients in relation to possible long-term neural alterations with a specific interest in the underlying autoimmune process. Eighteen patients with treated hypothyroidism due to Hashimoto's thyroiditis (mean age 32, range 18-54 years; two males; mean treatment duration 4.4 years) and 18 healthy matched control subjects underwent 3-Tesla magnetic resonance imaging (MRI). Voxel-based morphometry was used to investigate grey matter density, resting-state functional MRI to analyse the brain connectivity of areas known to be altered in hypothyroidism and event-related functional MRI to examine brain activity during associative memory encoding. Neuropsychological assessment included memory, working memory, psychomotor speed and attention. We previously reported subclinically reduced mood in this study population and investigated its neural correlates here. Thyroid stimulating hormone, free triiodthyronine, free thyroxine and thyroid peroxidase antibodies were measured in serum. We did not find cognitive deficits or alterations in grey matter density, functional connectivity or associative memory-related brain activity in comparison to the control group and cognition was unrelated to thyroid serum measures in the patient group. Thyroid peroxidase antibodies in the patient group correlated with increased grey matter density in right amygdala and enhanced connectivity between subcallosal and parahippocampal areas. Treatment duration was associated with brain structure in frontal and occipital cortex and connectivity between left amygdala and frontal cortex. Mood correlated with brain areas associated with distinct functional networks, but not with those most prominently affected in depression. In conclusion, no cognitive or neural alterations were detected in this young and otherwise healthy cohort of patients in comparison to a healthy control group and current mood status could not be related to depression-related networks. However, autoimmune activity and treatment duration showed a relationship with depression and hypothyroidism-related brain structure and function. They are thus promising factors to further investigate residual complaints despite biochemically adequate treatment in patients with Hashimoto's thyroiditis. Given the small sample size, all findings require replication.

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BACKGROUND: Disease-specific patient-reported outcome measures (PROMs) have been developed as important research tools in the study of various diseases. For hypothyroidism there exist three validated disease-specific questionnaires in English: the Thyroid-Dependent Quality of Life Questionnaire (ThyDQoL), the Underactive Thyroid Symptom Rating Questionnaire (ThySRQ) and the Thyroid Treatment Satisfaction Questionnaire (ThyTSQ). We report psychometric properties of new German versions of the questionnaires including construct validity from two independent samples. METHODS: 230 envelopes with ThyDQoL, ThySRQ and ThyTSQ were given out to patients receiving levothyroxine for diagnosed hypothyroidism. Reliability and factor analyses were performed, correlations and hypothesised subgroup differences calculated to assess psychometric properties. Independently, 18 patients with treated hypothyroidism for autoimmune thyroiditis (Hashimoto's disease) and 18 healthy control subjects were enrolled in a clinical study. Participants filled in the above questionnaires alongside well-known generic PROMs, e.g. the Beck Depression Inventory, the 12-item Well-Being Questionnaire and the Short-Form-36. Two blood samples were taken. Groups were compared and correlations between disease-specific and generic instruments analysed. Relationships between PROMs and biochemically determined thyroid hormone status were investigated. RESULTS: 102 patients returned completed questionnaires (response rate 44%). The newly translated questionnaires had satisfactory psychometric properties. Cronbach's alpha was 0.92 for ThyDQoL, 0.81 for ThySRQ and 0.86 for ThyTSQ. For each of the questionnaires, a single factor structure explained the data best. Adequately treated patients with thyroid stimulating hormone levels in the upper normal range reported more symptoms in the ThySRQ. Those with autoimmune hypothyroidism reported being more bothered by depressive symptoms. Within the clinical sample, correlation with well-known generic instruments revealed good construct validity. In the clinical sample patients reported more symptoms in the ThySRQ, being more bothered by tiredness, higher depression and reduced well-being despite biochemically adequate treatment. Correlations between PROMs and biochemical thyroid hormone status revealed moderate though consistent associations. CONCLUSIONS: Psychometric properties including construct validity of German versions of the ThyDQoL, ThySRQ and ThyTSQ are satisfactory. Feasibility and sensitivity in a clinical sample could be shown. We encourage the use of disease-specific PROMs in future studies as important additions to generic instruments in clinical research on hypothyroidism.

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Cerebral microangiopathy (CMA) has been associated with executive dysfunction and fronto-parietal neural network disruption. Advances in magnetic resonance imaging allow more detailed analyses of gray (e.g., voxel-based morphometry-VBM) and white matter (e.g., diffusion tensor imaging-DTI) than traditional visual rating scales. The current study investigated patients with early CMA and healthy control subjects with all three approaches. Neuropsychological assessment focused on executive functions, the cognitive domain most discussed in CMA. The DTI and age-related white matter changes rating scales revealed convergent results showing widespread white matter changes in early CMA. Correlations were found in frontal and parietal areas exclusively with speeded, but not with speed-corrected executive measures. The VBM analyses showed reduced gray matter in frontal areas. All three approaches confirmed the hypothesized fronto-parietal network disruption in early CMA. Innovative methods (DTI) converged with results from conventional methods (visual rating) while allowing greater spatial and tissue accuracy. They are thus valid additions to the analysis of neural correlates of cognitive dysfunction. We found a clear distinction between speeded and nonspeeded executive measures in relationship to imaging parameters. Cognitive slowing is related to disease severity in early CMA and therefore important for early diagnostics.

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