Structural Learning in Autistic and Non-Autistic Children: A Replication and Extension.

The hippocampus is involved in many cognitive domains which are difficult for autistic individuals. Our previous study using a Structural Learning task that has been shown to depend on hippocampal functioning found that structural learning is diminished in autistic adults (Ring et al., 2017). The aim of the present study was to examine whether those results can be replicated in and extended to a sample of autistic and non-autistic children. We tested 43 autistic children and 38 non-autistic children with a subsample of 25 autistic and 28 non-autistic children who were well-matched on IQ. The children took part in a Simple Discrimination task which a simpler form of compound learning, and a Structural Learning task. We expected both groups to perform similarly in Simple Discrimination but reduced performance by the autism group on the Structural Learning task, which is what we found in both the well-matched and the non-matched sample. However, contrary to our prediction and the findings from autistic adults in our previous study, autistic children demonstrated a capacity for Structural Learning and showed an overall better performance in the tasks than was seen in earlier studies. We discuss developmental differences in autism as well as the role of executive functions that may have contributed to better than predicted task performance in this study.

Caring for a child with cancer: Parental competence, distress, and cortisol levels.

Parents of children facing cancer are subject to psychological distress. In this study, we explored whether the time that had passed since a child's cancer diagnosis was associated with parents' distress levels and whether parental sense of competence (PSOC) moderated this association. Forty-four parents of children with cancer who were hospitalized during 2022 participated. Parents completed questionnaires and provided hair samples for the examination of hair cortisol concentration (HCC). Correlations indicated no significant association between time since diagnosis and distress indices. Yet, linear regression analysis revealed that PSOC moderated the association between time since diagnosis and parental HCC (ß = -0.36, p < 0.05). For parents with low PSOC, time since diagnosis did not predict parental HCC. For parents with high PSOC, a longer time since diagnosis was associated with lower levels of parental HCC. Our results provide support for the clinical significance of PSOC as a target for intervention.

Catecholaminergic Modulation of Metacontrol Is Reflected by Changes in Aperiodic EEG Activity.

BACKGROUND: "Metacontrol" describes the ability to maintain an optimal balance between cognitive control styles that are either more persistent or more flexible. Recent studies have shown a link between metacontrol and aperiodic EEG patterns. The present study aimed to gain more insight into the neurobiological underpinnings of metacontrol by using methylphenidate (MPH), a compound known to increase postsynaptic catecholamine levels and modulate cortical noise. METHODS: In a double-blind, randomized, placebo-controlled study design, we investigated the effect of MPH (0.5 mg/kg) on aperiodic EEG activity during a flanker task in a sample of n = 25 neurotypical adults. To quantify cortical noise, we employed the fitting oscillations and one over f algorithm. RESULTS: Compared with placebo, MPH increased the aperiodic exponent, suggesting that it reduces cortical noise in 2 ways. First, it did so in a state-like fashion, as the main effect of the drug was visible and significant in both pre-trial and within-trial periods. Second, the electrode-specific analyses showed that the drug also affects specific processes by dampening the downregulation of noise in conditions requiring more control. CONCLUSIONS: Our findings suggest that the aperiodic exponent provides a neural marker of metacontrol states and changes therein. Further, we propose that the effectiveness of medications targeting catecholaminergic signaling can be evaluated by studying changes of cortical noise, fostering the idea of using the quantification of cortical noise as an indicator in pharmacological treatment.

Exaggerated frontoparietal control over cognitive effort-based decision-making in young women with anorexia nervosa.

Effortful tasks are generally experienced as costly, but the value of work varies greatly across individuals and populations. While most mental health conditions are characterized by amotivation and effort avoidance, individuals with anorexia nervosa (AN) persistently engage in effortful behaviors that most people find unrewarding (food restriction, excessive exercise). Current models of AN differentially attribute such extreme weight-control behavior to altered reward responding and exaggerated cognitive control. In a novel test of these theoretical accounts, we employed an established cognitive effort discounting paradigm in combination with fMRI in young acutely underweight female patients with AN (n = 48) and age-matched healthy controls (HC; n = 48). Contrary to the hypothesis that individuals with AN would experience cognitive effort (operationalized as N-back task performance) as less costly than HC participants, groups did not differ in the subjective value (SV) of discounted rewards or in SV-related activation of brain regions involved in reward valuation. Rather, all group differences in both behavior (superior N-back performance in AN and associated effort ratings) and fMRI activation (increased SV-related frontoparietal activation during decision-making in AN even for easier choices) were more indicative of increased control. These findings suggest that while effort discounting may be relatively intact in AN, effort investment is high both when performing demanding tasks and during effort-based decision-making; highlighting cognitive overcontrol as an important therapeutic target. Future research should establish whether exaggerated control during effort-based decision-making persists after weight-recovery and explore learning the value of effort in AN with tasks involving disorder-relevant effort demands and rewards.

Indicated Prevention for Children Screened in Routine Health Care: Effectiveness of a Social Skills Program on Social Anxiety and Depressive Symptoms.

Social anxiety is common in childhood and potentially transitions into clinical disorders including depression. The present study aimed to examine the effectiveness of an indicated prevention program for children screened in routine care. Data came from the PROMPt project, a prospective implementation study (10/2018-09/2022) that explored a novel care chain, starting with screening with the Strengths and Difficulties Questionnaire (SDQ) as part of regular health check-ups, followed by indicated assignment and participation in a prevention program. Questionnaires assessing anxiety and depression symptoms were administered shortly after screening or before program participation (T0), six months after screening or after program participation (T1) and at a follow-up, six months after T1 (T2). Children who participated in a group cognitive-behavioral social skills program (TT; n = 145) were compared using mixed model analyses with non-participating children who were either screened as normal (NOR; n = 894) or refused program participation despite indication (NoTT; n = 67). TT scores improved from T0 to T1 compared to NOR and NoTT (anxiety ß = -0.71 and ß = -0.71, social anxiety ß = -0.46 and ß = -0.52, depression ß = -0.52 and ß = -0.73). Improvement was maintained at T2. Moderation analyses showed a trend toward greater benefit for participants with higher baseline scores. Indicated prevention can improve anxiety and depression symptoms in children identified by screening in routine care. Systematic screening and targeted prevention may positively affect mental health of children on a population level.

Automated Video-Based Approach for the Diagnosis of Tourette Syndrome.

BACKGROUND: The occurrence of tics is the main basis for the diagnosis of Gilles de la Tourette syndrome (GTS). Video-based tic assessments are time consuming. OBJECTIVE: The aim was to assess the potential of automated video-based tic detection for discriminating between videos of adults with GTS and healthy control (HC) participants. METHODS: The quantity and temporal structure of automatically detected tics/extra movements in videos from adults with GTS (107 videos from 42 participants) and matched HCs were used to classify videos using cross-validated logistic regression. RESULTS: Videos were classified with high accuracy both from the quantity of tics (balanced accuracy of 87.9%) and the number of tic clusters (90.2%). Logistic regression prediction probability provides a graded measure of diagnostic confidence. Expert review of about 25% of lower-confidence predictions could ensure an overall classification accuracy above 95%. CONCLUSIONS: Automated video-based methods have a great potential to support quantitative assessment and clinical decision-making in tic disorders.

The impact of the COVID-19 pandemic on administrative eating disorder prevalence in the outpatient sector and on severity of anorexia nervosa.

The COVID-19 pandemic appears to have had a considerable impact on the mental health of children and adolescents, particularly regarding eating disorders. However, it remains unclear whether the pandemic affected only the frequency or also the severity of eating disorders. We examined potential pandemic-related changes in the administrative prevalence of eating disorders in the outpatient sector compared with other mental disorders using German statutory health insurance data for the age group 10 to 16 years. We also examined disorder severity of anorexia nervosa using data from the multicenter German Registry of Children and Adolescents with Anorexia Nervosa in the same age group. Our results showed a marked increase in the administrative prevalence of eating disorders (based on documented diagnoses) in the outpatient sector among girls but not among boys. A similar pattern was found for internalizing disorders, whereas the administrative prevalences of externalizing disorders decreased. Regarding the severity of anorexia nervosa among inpatients, we found no pandemic-related changes in body mass index standard deviation score at admission, body weight loss before admission, psychiatric comorbidities and psychopharmacological medication. Given the administrative prevalence increase in the outpatient sector, the lack of impact of the pandemic on the inpatient sector may also be partly due to a shift in healthcare utilization towards outpatient services during the pandemic. Thus, the higher number of children and adolescents requiring specialized and timely outpatient care may be a major concern under pandemic conditions.

The metacontrol of event segmentation-A neurophysiological and behavioral perspective.

During our everyday life, the constant flow of information is divided into discrete events, a process conceptualized in Event Segmentation Theory (EST). How people perform event segmentation and the resulting granularity of encapsulated segments likely depends on their metacontrol style. Yet, the underlying neural mechanisms remain undetermined. The current study examines how the metacontrol style affects event segmentation through the analysis of EEG data using multivariate pattern analysis (MVPA) and source localization analysis. We instructed two groups of healthy participants to either segment a movie as fine-grained as possible (fine-grain group) or provided no such instruction (free-segmentation group). The fine-grain group showed more segments and a higher likelihood to set event boundaries upon scene changes, which supports the notion that cognitive control influences segmentation granularity. On a neural level, representational dynamics were decodable 400 ms prior to the decision to close a segment and open a new one, and especially fronto-polar regions (BA10) were associated with this representational dynamic. Groups differed in their use of this representational dynamics to guide behavior and there was a higher sensitivity to incoming information in the Fine-grain group. Moreover, a higher likelihood to set event boundaries was reflected by activity increases in the insular cortex suggesting an increased monitoring of potentially relevant upcoming events. The study connects the EST with the metacontrol framework and relates these to overarching neural concepts of prefrontal cortex function.

Retrospective assessment of ICD-10/DSM-5 criteria of childhood ADHD from descriptions of academic and social behaviors in German primary school reports.

BACKGROUND: The diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adolescence and adulthood is particularly challenging because retrospective confirmation of previous childhood ADHD is mandatory. Therefore, collecting valid diagnostic information about behavior at school is important. Primary school reports often contain descriptions of academic performance and social behaviors associated with ADHD criteria. Yet, there is no systematic approach available how to assess such reports quantitatively, and therefore, there is also no study on how valid such an approach could predict an ADHD diagnosis. METHODS: We examined primary school reports from Germany (ADHD: n = 1197, typically developing controls: n = 656) for semantic references to ICD-10/DSM-5 main and sub-criteria of ADHD. Descriptions were assessed on a quantitative scale (blinded clinical expert rating) for disorder-associated behaviors (symptoms scale) as well as for desired, adaptive behaviors (competencies scale) according to these criteria. The scores of these developed scales have been summarized to summary scores. Scores were analyzed using linear mixed models, and sensitivity and specificity were estimated using receiver operating characteristics (ROC). RESULTS: Ratings showed highly significant differences between school reports of children with and without ADHD. For the summary scores, both symptoms and competencies scales showed high diagnostic accuracy (ROC area under the curve at least 0.96) with best discrimination when combining both into an integrated index (sensitivity and specificity > 0.97). CONCLUSIONS: Our findings suggest that systematic quantitative analysis of primary school reports should be further explored to construct a valid instrument for retrospective assessment of childhood ADHD criteria to aid the diagnostic process in adolescents and adults.

How culture affects the way in which psychopathologies manifest in behavior: The case of Confucianism in China.

BACKGROUND: Internalizing disorders in children and adolescents are about as frequent as externalizing disorders in the US, but three times more prevalent than externalizing disorders in China. AIMS: To examine why and how mental predispositions and stress lead to psychopathology in general and manifest as internalizing or externalizing problems in particular, and which role intercultural differences may play in understanding this. METHOD: A review of the literature. RESULTS/CONCLUSIONS: The interplay of personal freedom and societal duties in an individual's development crucially influences whether psychopathologies appear as externalizing or internalizing issues. Eastern and especially Chinese cultures have long favored societal obligations over individual autonomy, guided by Confucian principles, promoting internalization over externalization. Understanding culture's role in behavior can improve mental healthcare by fostering tailored, culturally informed interventions for children and adolescents.

Neural connectivity patterns explain why adolescents perceive the world as moving slow.

That younger individuals perceive the world as moving slower than adults is a familiar phenomenon. Yet, it remains an open question why that is. Using event segmentation theory, electroencephalogram (EEG) beamforming and nonlinear causal relationship estimation using artificial neural network methods, we studied neural activity while adolescent and adult participants segmented a movie. We show when participants were instructed to segment a movie into meaningful units, adolescents partitioned incoming information into fewer encapsulated segments or episodes of longer duration than adults. Importantly, directed communication between medial frontal and lower-level perceptual areas and between occipito-temporal regions in specific neural oscillation spectrums explained behavioral differences between groups. Overall, the study reveals that a different organization of directed communication between brain regions and inefficient transmission of information between brain regions are key to understand why younger people perceive the world as moving slow.

Assessment of affective dysregulation in children: development and evaluation of a semi-structured interview for parents and for children.

BACKGROUND: Children with affective dysregulation (AD) show an excessive reactivity to emotionally positive or negative stimuli, typically manifesting in chronic irritability, severe temper tantrums, and sudden mood swings. AD shows a large overlap with externalizing and internalizing disorders. Given its transdiagnostic nature, AD cannot be reliably and validly captured only by diagnostic categories such as disruptive mood dysregulation disorder (DMDD). Therefore, this study aimed to evaluate two semi-structured clinical interviews-one for parents and one for children. METHODS: Both interviews were developed based on existing measures that capture particular aspects of AD. We analyzed internal consistencies and interrater agreement to evaluate their reliability. Furthermore, we analyzed factor loadings in an exploratory factor analysis, differences in interview scores between children with and without co-occurring internalizing and externalizing disorders, and associations with other measures of AD and of AD-related constructs. The evaluation was performed in a screened community sample of children aged 8-12 years (n = 445). Interrater reliability was additionally analyzed in an outpatient sample of children aged 8-12 years (n = 27). RESULTS: Overall, internal consistency was acceptable to good. In both samples, we found moderate to excellent interrater reliability on a dimensional level. Interrater agreement for the dichotomous diagnosis DMDD was substantial to perfect. In the exploratory factor analysis, almost all factor loadings were acceptable. Children with a diagnosis of disruptive disorder, attention-deficit/hyperactivity disorder, or any disorder (disruptive disorder, attention-deficit/hyperactivity disorder, and depressive disorder) showed higher scores on the DADYS interviews than children without these disorders. The correlation analyses revealed the strongest associations with other measures of AD and measures of AD-specific functional impairment. Moreover, we found moderate to very large associations with internalizing and externalizing symptoms and moderate to large associations with emotion regulation strategies and health-related quality of life. CONCLUSIONS: The analyses of internal consistency and interrater agreement support the reliability of both clinical interviews. Furthermore, exploratory factor analysis, discriminant analyses, and correlation analyses support the interviews' factorial, discriminant, concurrent, convergent, and divergent validity. The interviews might thus contribute to the reliable and valid identification of children with AD and the assessment of treatment responses. TRIAL REGISTRATION: ADOPT Online: German Clinical Trials Register (DRKS) DRKS00014963. Registered 27 June 2018.

Event segmentation in ADHD: neglect of social information and deviant theta activity point to a mechanism underlying ADHD.

Background: Attention-deficit/hyperactivity disorder (ADHD) is one of the most frequently diagnosed psychiatric conditions in children and adolescents. Although the symptoms appear to be well described, no coherent conceptual mechanistic framework integrates their occurrence and variance and the associated problems that people with ADHD face. Aims: The current study proposes that altered event segmentation processes provide a novel mechanistic framework for understanding deficits in ADHD. Methods: Adolescents with ADHD and neurotypically developing (NT) peers watched a short movie and were then asked to indicate the boundaries between meaningful segments of the movie. Concomitantly recorded electroencephalography (EEG) data were analysed for differences in frequency band activity and effective connectivity between brain areas. Results: Compared with their NT peers, the ADHD group showed less dependence of their segmentation behaviour on social information, indicating that they did not consider social information to the same extent as their unaffected peers. This divergence was accompanied by differences in EEG theta band activity and a different effective connectivity network architecture at the source level. Specifically, NT adolescents primarily showed error signalling in and between the left and right fusiform gyri related to social information processing, which was not the case in the ADHD group. For the ADHD group, the inferior frontal cortex associated with attentional sampling served as a hub instead, indicating problems in the deployment of attentional control. Conclusions: This study shows that adolescents with ADHD perceive events differently from their NT peers, in association with a different brain network architecture that reflects less adaptation to the situation and problems in attentional sampling of environmental information. The results call for a novel conceptual view of ADHD, based on event segmentation theory.

Altered neural anticipation of reward and loss but not receipt in adolescents with obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by persistent, unwanted thoughts and repetitive actions. Such repetitive thoughts and/or behaviors may be reinforced either by reducing anxiety or by avoiding a potential threat or harm, and thus may be rewarding to the individual. The possible involvement of the reward system in the symptomatology of OCD is supported by studies showing altered reward processing in reward-related regions, such as the ventral striatum (VS) and the orbitofrontal cortex (OFC), in adults with OCD. However, it is not clear whether this also applies to adolescents with OCD. METHODS: Using functional magnetic resonance imaging, two sessions were conducted focusing on the anticipation and receipt of monetary reward (1) or loss (2), each contrasted to a verbal (control) condition. In each session, adolescents with OCD (n1=31/n2=26) were compared with typically developing (TD) controls (n1=33/ n2=31), all aged 10-19 years, during the anticipation and feedback phase of an adapted Monetary Incentive Delay task. RESULTS: Data revealed a hyperactivation of the VS, but not the OFC, when anticipating both monetary reward and loss in the OCD compared to the TD group. CONCLUSIONS: These findings suggest that aberrant neural reward and loss processing in OCD is associated with greater motivation to gain or maintain a reward but not with the actual receipt. The greater degree of reward 'wanting' may contribute to adolescents with OCD repeating certain actions more and more frequently, which then become habits (i.e., OCD symptomatology).

Slips of the tongue in patients with Gilles de la Tourette syndrome.

BACKGROUND: Motor and vocal tics are the main symptom of Gilles de la Tourette-syndrome (GTS). A particular complex vocal tic comprises the utterance of swear words, termed coprolalia. Since taboo words are socially inappropriate, they are normally suppressed by people, which implies cognitive control processes. METHOD: To investigate the control of the unintentional pronunciation of taboo words and the associated processes of conflict monitoring, we used the "Spoonerisms of Laboratory Induced Predisposition" (SLIP) paradigm. Participants read multiple inductor word pairs with the same phonemes, followed by pronouncing a target pair with inverse phonemes. This led to a conflict between two competing speech plans: the correct word pair and the word pair with inverted phonemes. Latter speech error, a spoonerism, could result in a neutral or taboo word. We investigated 19 patients with GTS and 23 typically developed controls (TDC) and measured participants' electroencephalography (EEG) during the SLIP task. RESULTS: At the behavioral level less taboo than neutral word spoonerisms occurred in both groups without significant differences. Event-related brain potentials (ERP) revealed a difference between taboo and neutral word conditions in the GTS group at the midline electrodes in a time range of 250-400 ms after the speech prompt, which was not found in the TDC group. The extent of this effect depended on the number of inductor word pairs, suggesting an increasing level of cognitive control in the GTS group. CONCLUSION: The differences between taboo and neutral word conditions in patients with GTS compared to TDC suggest an altered recruitment of cognitive control processes in GTS, likely enlisted to suppress taboo words.

Effects of Catecholaminergic and Transcranial Direct Current Stimulation on Response Inhibition.

BACKGROUND: The principle of gain control determines the efficiency of neuronal processing and can be enhanced with pharmacological or brain stimulation methods. It is a key factor for cognitive control, but the degree of how much gain control may be enhanced underlies a physical limit. METHODS: To investigate whether methylphenidate (MPH) and transcranial direct current stimulation (tDCS) share common underlying mechanisms and cognitive effects, we administered MPH and anodal tDCS (atDCS) over the right inferior frontal gyrus both separately and combined, while healthy adult participants (n = 104) performed a response selection and inhibition task. The recorded EEG data were analyzed with a focus on theta band activity, and source estimation analyses were conducted. RESULTS: The behavioral data show that MPH and atDCS revealed interactive effects on the ability to inhibit responses. Both MPH and atDCS modulated task-related theta oscillations in the supplementary motor area when applied separately, making a common underlying mechanism likely. When both stimulation methods were combined, there was no doubling of effects in the supplementary motor area but a shift to inferior frontal areas in the cortical network responsible for theta-driven processing. CONCLUSIONS: The results indicate that both MPH and atDCS likely share a common underlying neuronal mechanism, and interestingly, they demonstrate interactive effects when combined, which are most likely due to the physical limitations of gain control increases. The current study provides critical groundwork for future combined applications of MPH and non-invasive brain stimulation.

The impact of depressive and anxious symptoms on quality of life in adults on the autism spectrum.

Quality of life (QoL) is lower in adults on the autism spectrum (AS) compared with typically developing (TD) adults. In this context, recent studies have examined the role of depression and anxiety in reducing QoL in AS adults. The aim of this study was to (1) replicate these findings of lower QoL and (2) assess the negative influence of depressive and anxious symptoms on QoL in an adult AS (N = 86) and TD (N = 87) German sample with a broad age range (18-70 years). For this, we used questionnaires that have been validated for the AS and TD population: the World Health Organization Quality of Life Brief Version, the Autism-Specific QoL items, and the Hospital Anxiety and Depression Scale. We replicated previous findings and extended them to autism-specific QoL. Our AS sample had lower QoL compared with the TD adults. However, depressive symptoms were the largest contributor to lower QoL in both samples, more so than group membership and anxious symptoms. We conclude that interventions to improve QoL in AS adults should specifically target depressive symptoms and for this, improvements to the diagnostic process and treatment of depression in AS are necessary.

Interactions of catecholamines and GABA+ in cognitive control: Insights from EEG and 1H-MRS.

Catecholamines and amino acid transmitter systems are known to interact, the exact links and their impact on cognitive control functions have however remained unclear. Using a multi-modal imaging approach combining EEG and proton-magnetic resonance spectroscopy (1H-MRS), we investigated the effect of different degrees of pharmacological catecholaminergic enhancement onto theta band activity (TBA) as a measure of interference control during response inhibition and execution. It was central to our study to evaluate the predictive impact of in-vivo baseline GABA+ concentrations in the striatum, the anterior cingulate cortex (ACC) and the supplemental motor area (SMA) of healthy adults under varying degrees of methylphenidate (MPH) stimulation. We provide evidence for a predictive interrelation of baseline GABA+ concentrations in cognitive control relevant brain areas onto task-induced TBA during response control stimulated with MPH. Baseline GABA+ concentrations in the ACC, the striatum, and the SMA had a differential impact on predicting interference control-related TBA in response execution trials. GABA+ concentrations in the ACC appeared to be specifically important for TBA modulations when the cognitive effort needed for interference control was high - that is when no prior task experience exists, or in the absence of catecholaminergic enhancement with MPH. The study highlights the predictive role of baseline GABA+ concentrations in key brain areas influencing cognitive control and responsiveness to catecholaminergic enhancement, particularly in high-effort scenarios.

Longitudinal changes in brain-derived neurotrophic factor (BDNF) but not cytokines contribute to hippocampal recovery in anorexia nervosa above increases in body mass index.

BACKGROUND: Physical sequelae of anorexia nervosa (AN) include a marked reduction in whole brain volume and subcortical structures such as the hippocampus. Previous research has indicated aberrant levels of inflammatory markers and growth factors in AN, which in other populations have been shown to influence hippocampal integrity. METHODS: Here we investigated the influence of concentrations of two pro-inflammatory cytokines (tumor necrosis factor-alpha [TNF-α] and interleukin-6 [IL-6]) and brain-derived neurotrophic factor (BDNF) on the whole hippocampal volume, as well as the volumes of three regions (the hippocampal body, head, and tail) and 18 subfields bilaterally. Investigations occurred both cross-sectionally between acutely underweight adolescent/young adult females with AN (acAN; n = 82) and people recovered from AN (recAN; n = 20), each independently pairwise age-matched with healthy controls (HC), and longitudinally in acAN after partial renourishment (n = 58). Hippocampal subfield volumes were quantified using FreeSurfer. Concentrations of molecular factors were analyzed in linear models with hippocampal (subfield) volumes as the dependent variable. RESULTS: Cross-sectionally, there was no evidence for an association between IL-6, TNF-α, or BDNF and between-group differences in hippocampal subfield volumes. Longitudinally, increasing concentrations of BDNF were positively associated with longitudinal increases in bilateral global hippocampal volumes after controlling for age, age2, estimated total intracranial volume, and increases in body mass index (BMI). CONCLUSIONS: These findings suggest that increases in BDNF may contribute to global hippocampal recovery over and above increases in BMI during renourishment. Investigations into treatments targeted toward increasing BDNF in AN may be warranted.