More by stick than by carrot: A reinforcement learning style rooted in the medial frontal cortex in anorexia nervosa.

Anorexia nervosa (AN) is characterized by a relentless pursuit of thinness, despite serious implications for health and social relations. In a previous study wielding the power of computational psychiatry, we found alterations in learning from negative feedback and in neural activity in the posterior medial frontal cortex (pMFC) in young acutely underweight AN patients (acAN). Here we ask whether these abnormalities are merely a state-related consequence of the illness or whether they might constitute a trait marker predisposing individuals to AN. To address this question, we employed the same reinforcement learning paradigm during fMRI with 31 female former AN patients after complete weight-recovery (recAN) and 31 age-matched healthy volunteers (15-28 years). Participants performed a decision task that required adaptation to changing reward contingencies. Data were analyzed within a hierarchical Gaussian filter model, which captures interindividual variability in feedback learning and decision-making under uncertainty. Similar to acute patients, individuals recovered from AN appear to emphasize negative over positive feedback when updating expectations regarding changing reward-punishment contingencies (difference in learning rate between punished and rewarded trials was increased in recAN: p = .006, d = .70. This behavioral pattern was mirrored in hyperactivation of the pMFC following negative feedback (FWE p < .001). Because the previously observed alterations in acANs are also evident after recovery and do not correlate with state variables like weight, altered feedback learning might be a trait marker of AN. The neural underpinnings of these alterations may lie in the pMFC. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Altered Medial Frontal Feedback Learning Signals in Anorexia Nervosa.

BACKGROUND: In their relentless pursuit of thinness, individuals with anorexia nervosa (AN) engage in maladaptive behaviors (restrictive food choices and overexercising) that may originate in altered decision making and learning. METHODS: In this functional magnetic resonance imaging study, we employed computational modeling to elucidate the neural correlates of feedback learning and value-based decision making in 36 female patients with AN and 36 age-matched healthy volunteers (12-24 years). Participants performed a decision task that required adaptation to changing reward contingencies. Data were analyzed within a hierarchical Gaussian filter model that captures interindividual variability in learning under uncertainty. RESULTS: Behaviorally, patients displayed an increased learning rate specifically after punishments. At the neural level, hemodynamic correlates for the learning rate, expected value, and prediction error did not differ between the groups. However, activity in the posterior medial frontal cortex was elevated in AN following punishment. CONCLUSIONS: Our findings suggest that the neural underpinning of feedback learning is selectively altered for punishment in AN.

mTOR inhibitor reverses autistic-like social deficit behaviours in adult rats with both Tsc2 haploinsufficiency and developmental status epilepticus.

Epilepsy is a major risk factor for autism spectrum disorder (ASD) and complicates clinical manifestations and management of ASD significantly. Tuberous sclerosis complex (TSC), caused by TSC1 or TSC2 mutations, is one of the medical conditions most commonly associated with ASD and has become an important model to examine molecular pathways associated with ASD. Previous research showed reversal of autism-like social deficits in Tsc1 +/- and Tsc2 +/- mouse models by mammalian target of rapamycin (mTOR) inhibitors. However, at least 70 % of individuals with TSC also have epilepsy, known to complicate the severity and treatment responsiveness of the behavioural phenotype. No previous study has examined the impact of seizures on neurocognitive reversal by mTOR inhibitors. Adult Tsc2 +/- (Eker)-rats express social deficits similar to Tsc2 +/- mice, with additive social deficits from developmental status epilepticus (DSE). DSE was induced by intraperitoneal injection with kainic acid at post-natal days P7 and P14 (n = 12). The experimental group that modelled TSC pathology carried the Tsc2 +/- (Eker)-mutation and was challenged with DSE. The wild-type controls had not received DSE (n = 10). Four-month-old animals were analysed for social behaviour (T1), then treated three times during 1 week with 1 mg/kg everolimus and finally retested in the post-treatment behavioural analysis (T2). In the experimental group, both social interaction and social cognition were impaired at T1. After treatment at T2, behaviour in the experimental group was indistinguishable from controls. The mTOR inhibitor, everolimus, reversed social deficit behaviours in the Tsc2 haploinsufficiency plus DSE animal model to control levels.

Genetic underpinnings of left superior temporal gyrus thickness in patients with schizophrenia.

OBJECTIVES: Schizophrenia is a highly disabling psychiatric disorder with a heterogeneous phenotypic appearance. We aimed to further the understanding of some of the underlying genetics of schizophrenia, using left superior temporal gyrus (STG) grey matter thickness reduction as an endophenoptype in a genome-wide association (GWA) study. METHODS: Structural magnetic resonance imaging (MRI) and genetic data of the Mind Clinical Imaging Consortium (MCIC) study of schizophrenia were used to analyse the interaction effects between 1,067,955 single nucleotide polymorphisms (SNPs) and disease status on left STG thickness in 126 healthy controls and 113 patients with schizophrenia. We next used a pathway approach to detect underlying pathophysiological pathways that may be related to schizophrenia. RESULTS: No SNP by diagnosis interaction effect reached genome-wide significance (5 × 10-8) in our GWA study, but 10 SNPs reached P-values less than 10-6. The most prominent pathways included those involved in insulin, calcium, PI3K-Akt and MAPK signalling. CONCLUSIONS: Our strongest findings in the GWA study and pathway analysis point towards an involvement of glucose metabolism in left STG thickness reduction in patients with schizophrenia only. These results are in line with recently published studies, which showed an increased prevalence of psychosis among patients with metabolic syndrome-related illnesses including diabetes.

Olfactory short-term memory encoding and maintenance - an event-related potential study.

This study examined whether the memory encoding and short term maintenance of olfactory stimuli is associated with neurophysiological activation patterns which parallel those described for sensory modalities such as vision and auditory. We examined olfactory event-related potentials in an olfactory change detection task in twenty-four healthy adults and compared the measured activation to that found during passive olfactory stimulation. During the early olfactory post-processing phase, we found a sustained negativity over bilateral frontotemporal areas in the passive perception condition which was enhanced in the active memory task. There was no significant lateralization in either experimental condition. During the maintenance interval at the end of the delay period, we still found sustained activation over bilateral frontotemporal areas which was more negative in trials with correct - as compared to incorrect - behavioural responses. This was complemented by a general significantly stronger frontocentral activation. Summarizing, we were able to show that olfactory short term memory involves a parallel sequence of activation as found in other sensory modalities. In addition to olfactory-specific frontotemporal activations in the memory encoding phase, we found slow cortical potentials over frontocentral areas during the memory maintenance phase indicating the activation of a supramodal memory maintenance system. These findings could represent the neurophysiological underpinning of the 'olfactory flacon', the olfactory counter-part to the visual sketchpad and phonological loop embedded in Baddeley's working memory model.

Who wants to become a child psychiatrist? Lessons for future recruitment strategies from a student survey at seven German medical schools.

OBJECTIVE: The objective of this survey was to investigate undergraduate German medical students' attitudes toward child and adolescent psychiatry (CAP) and to describe the characteristics of students considering CAP as a possible career choice. METHODS: The authors conducted a cross-sectional, multicenter survey of medical students (at the time of their first CAP lecture) at seven German medical schools. The students completed an anonymous self-report questionnaire, asking about their attitude toward CAP and their view of CAP as a possible career choice. RESULTS: Of the 574 students, 42.9% had "high" or "very high" interest in CAP, and 59.4% rated CAP basic knowledge as "highly" or "very highly" relevant for their prospective work as physicians. CAP was a possible career choice for 25.4%. The most frequently mentioned reasons for choosing CAP were interesting clinical cases (65.8%), helping ill children (52.1%), and close patient-physician contact (50.7%). The most frequently mentioned reasons against this decision were a definite decision for another subspecialty (54.8%), expected difficulties in working with parents and family members (35.3%), and an expected high emotional burden (29.6%). In addition to the highly significant correlation with general interest in CAP, students with previous experience in general psychiatry and CAP clinical courses, as well as female students and students with relatives or acquaintances with CAP-related disorders, showed the highest interest in CAP as a possible career choice. CONCLUSION: The majority of the students surveyed showed a positive attitude toward CAP and considered CAP basic knowledge to be relevant for their future work. When designing recruitment strategies, it may be helpful to consider that CAP exposure early in the curriculum might be decisive and that students with previous clinical courses in this field, as well as female students, showed the highest interest in CAP as a possible career choice.

[What do medical students expect of lectures in child and adolescent psychiatry?]. / Was erwarten medizinstudierende von vorlesungen in der kinder- und jugendpsychiatrie?

OBJECTIVE: In child and adolescent psychiatry (CAP) lectures are the most common teaching format for medical students. Besides conveying basic knowledge and skills related to the medical management of children and adolescents with mental health problems, lectures also play a decisive role in the recruitment of future residents for this discipline. Thus, knowledge of the expectations of medical students of lectures is a crucial factor. METHOD: 1,029 medical students at ten German medical schools were surveyed with a questionnaire in a cross-sectional design. RESULTS: Items perceived as most important were knowledge of disorders (73 %), medical skills in handling children and adolescents (61 %), and differential diagnosis of normal and abnormal child behaviour in children and adolescents (59 %). 71 % set a high value on patient presentation, while 41 % expressed ethical concerns about presenting mentally ill minors in lectures. CONCLUSIONS: The expectations of medical students toward CAP lectures are mainly related to the transfer of specialty-related knowledge and generic skills. The important area of teaching attitudes could best be covered via patient presentations, which are desired by most students. However, ethical concerns over patient presentation also need to be discussed with students.

A new classification of the delusional misidentification syndromes.

In recent years, a great number of very different and in part contradictory terminologies and classifications of delusional misidentification syndromes (DMS) have been published. In various case reports, several authors have also made contradictory comments on questions concerning classification, etiology and assignment to a possible entity of DMS. Further development and extension of the classifications proposed during recent years did not help to eliminate discrepancies and contradictions. The classification presented here has not shown any inconsistencies so far and it allows the classification of any DMS that has been examined recently.