Jochen Seitz

Deviant processing of letters and speech sounds as proximate cause of reading failure: a functional magnetic resonance imaging study of dyslexic children

Learning to associate auditory information of speech sounds with visual information of letters is a first and critical step for becoming a skilled reader in alphabetic languages. Nevertheless, it remains largely unknown which brain areas subserve the learning and automation of such associations. Here, we employ functional magnetic resonance imaging to study letter-speech sound integration in children with and without developmental dyslexia. The results demonstrate that dyslexic children show reduced neural integration of letters and speech sounds in the planum temporale/Heschl sulcus and the superior temporal sulcus. While cortical responses to speech sounds in fluent readers were modulated by letter-speech sound congruency with strong suppression effects for incongruent letters, no such modulation was observed in the dyslexic readers. Whole-brain analyses of unisensory visual and auditory group differences additionally revealed reduced unisensory responses to letters in the fusiform gyrus in dyslexic children, as well as reduced activity for processing speech sounds in the anterior superior temporal gyrus, planum temporale/Heschl sulcus and superior temporal sulcus. Importantly, the neural integration of letters and speech sounds in the planum temporale/Heschl sulcus and the neural response to letters in the fusiform gyrus explained almost 40% of the variance in individual reading performance. These findings indicate that an interrelated network of visual, auditory and heteromodal brain areas contributes to the skilled use of letter-speech sound associations necessary for learning to read. By extending similar findings in adults, the data furthermore argue against the notion that reduced neural integration of letters and speech sounds in dyslexia reflect the consequence of a lifetime of reading struggle. Instead, they support the view that letter-speech sound integration is an emergent property of learning to read that develops inadequately in dyslexic readers, presumably as a result of a deviant interactive specialization of neural systems for processing auditory and visual linguistic inputs.

Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis

BACKGROUND Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis. METHODS In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156. FINDINGS Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohens d=-0·15), amygdala (d=-0·19), caudate (d=-0·11), hippocampus (d=-0·11), putamen (d=-0·14), and intracranial volume (d=-0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (<15 years) versus adults (>21 years): in the accumbens (Cohens d=-0·19 vs -0·10), amygdala (d=-0·18 vs -0·14), caudate (d=-0·13 vs -0·07), hippocampus (d=-0·12 vs -0·06), putamen (d=-0·18 vs -0·08), and intracranial volume (d=-0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5). INTERPRETATION With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. FUNDING National Institutes of Health.

The role of impulsivity, inattention and comorbid ADHD in patients with bulimia nervosa.

Introduction Little is known about the contribution of impulsivity, inattention and comorbid attention deficit/hyperactivity disorder (ADHD) in the development and maintenance of bulimia nervosa (BN). In particular, their specific contribution to disordered eating symptoms and whether they have additive effects to the general psychopathological burden remains unclear. Methods Fifty-seven female patients seeking treatment for BN and 40 healthy controls completed diagnostic questionnaires and interviews that investigated: a) ADHD, b) impulsivity, c) eating disorders and d) general psychopathology. Attentional processes and impulsivity were assessed by a comprehensive computer-based neuropsychological battery. Results Twenty-one percent of patients with BN met the clinical cut-off for previous childhood ADHD compared to 2.5% of healthy controls. Adult ADHD according to DSM IV was also more prevalent in patients with BN, with an odds ratio of 4.2. Patients with BN and previous childhood ADHD were more impulsive and inattentive than patients with BN alone. These patients also displayed more severely disordered eating patterns and more general psychopathological symptoms compared with those without ADHD. Severity of eating disorder symptoms was better explained by inattentiveness than by either impulsivity or hyperactivity. Discussion Our data suggest an elevated rate of former childhood and current ADHD-symptoms in treatment-seeking patients with BN. Stronger impulsivity and inattention associated with more severe neuropsychological deficits and eating disorder symptoms indicate an additive risk that is clinically relevant for these patients. Thus, clinicians should identify comorbid patients who might profit from additional ADHD-specific treatments.

Morphological Changes in the Brain of Acutely Ill and Weight-Recovered Patients with Anorexia Nervosa

OBJECTIVE Acute anorexia nervosa (AN) leads to reduced gray (GM) and white matter (WM) volume in the brain, which however improves again upon restoration of weight. Yet little is known about the extent and clinical correlates of these brain changes, nor do we know much about the time-course and completeness of their recovery. METHODS We conducted a meta-analysis and a qualitative review of all magnetic resonance imaging studies involving volume analyses of the brain in both acute and recovered AN. RESULTS We identified structural neuroimaging studies with a total of 214 acute AN patients and 177 weight-recovered AN patients. In acute AN, GM was reduced by 5.6% and WM by 3.8% compared to healthy controls (HC). Short-term weight recovery 2-5 months after admission resulted in restitution of about half of the GM aberrations and almost full WM recovery. After 2-8 years of remission GM and WM were nearly normalized, and differences to HC (GM: -1.0%, WM: -0.7%) were no longer significant, although small residual changes could not be ruled out. In the qualitative review some studies found GM volume loss to be associated with cognitive deficits and clinical prognosis. CONCLUSIONS GM and WM were strongly reduced in acute AN. The completeness of brain volume rehabilitation remained equivocal.

Eating disorders : the big issue

A new report from the King’s Fund entitled Bringing Together Physical and Mental Health: a New Frontier for Integrated Care not only reviews the case for integration, but also provides real practical examples of how it has been achieved. Importantly, the report describes both the barriers to and facilitators of its successful implementation on the basis of interviews of those involved. The barriers are many and not all will be overcome simply by colocation of services (colocation is not integration). They include deeply ingrained cultural factors in the workforce that reinforce division and the separate organisational and payment systems for physical and mental health care. Key facilitators to achievement of integration include strong leadership for change at both clinical and board level and a willingness to innovate in the relevant organisations. Policy developments in various countries, including the new models of care introduced by the National Health Service Five Year Forward View in England and the growth of accountable care organisations in the USA have the exciting potential to facilitate integration of physical and mental health care. However, this integration will only happen if psychiatrists and other professionals now actively engage with these developments and use them as opportunities to advocate for and lead new forms of collaborative or even integrated working. The idea of so-called parity of esteem for patients’ mental and physical health care, which has been successfully championed by the Royal College of Psychiatrists, has achieved considerable influence. Indeed, in England, the Health and Social Care Act 2012 created a new legal responsibility for the National Health Service to deliver parity of esteem between physical and mental health, something that the Government has pledged to achieve by 2020. However, interpretations of parity of esteem vary. One interpretation is simply for existing mental health services to be as well funded and provide as good care as existing physical health services. Although this interpretation is an important ambition, the report from the King’s Fund7 raises sights much higher than this ambition to a vision in which mental health care is not only as good as physical care is, but is also delivered as part of all health and care services. This challenge should be addressed and the opportunity seized if we are to repair the harm caused by 100 years of separation.

White matter microstructural changes in adolescent anorexia nervosa including an exploratory longitudinal study

Background Anorexia nervosa (AN) often begins in adolescence, however, the understanding of the underlying pathophysiology at this developmentally important age is scarce, impeding early interventions. We used diffusion tensor imaging (DTI) to investigate microstructural white matter (WM) brain changes including an experimental longitudinal follow-up. Methods We acquired whole brain diffusion-weighted brain scans of 22 adolescent female hospitalized patients with AN at admission and nine patients longitudinally at discharge after weight rehabilitation. Patients (10–18 years) were compared to 21 typically developing controls (TD). Tract-based spatial statistics (TBSS) were applied to compare fractional anisotropy (FA) across groups and time points. Associations between average FA values of the global WM skeleton and weight as well as illness duration parameters were analyzed by multiple linear regression. Results We observed increased FA in bilateral frontal, parietal and temporal areas in AN patients at admission compared to TD. Higher FA of the global WM skeleton at admission was associated with faster weight loss prior to admission. Exploratory longitudinal analysis showed this FA increase to be partially normalized after weight rehabilitation. Conclusions Our findings reveal a markedly different pattern of WM microstructural changes in adolescent AN compared to most previous results in adult AN. This could signify a different susceptibility and reaction to semi-starvation in the still developing brain of adolescents or a time-dependent pathomechanism differing with extend of chronicity. Higher FA at admission in adolescents with AN could point to WM fibers being packed together more closely.

Food matters: how the microbiome and gut–brain interaction might impact the development and course of anorexia nervosa

Anorexia nervosa (AN) is one of the most common chronic illnesses in female adolescents and exhibits the highest mortality risk of all psychiatric disorders. Evidence for the effectiveness of psychotherapeutic or psychopharmacological interventions is weak. Mounting data indicate that the gut microbiome interacts with the central nervous system and the immune system by neuroendocrine, neurotransmitter, neurotrophic and neuroinflammatory afferent and efferent pathways. There is growing evidence that the gut microbiota influences weight regulation and psychopathology, such as anxiety and depression. This article reviews how the gut–brain interaction may impact the development and course of AN. A “leaky gut”, characterized by antigens traversing the intestinal wall, was demonstrated in an animal model of AN, and could underlie the low-grade inflammation and increased risk of autoimmune diseases found in AN. Moreover, starvation has a substantial impact on the gut microbiome, and diets used for re-nutrition based on animal products may support the growth of bacteria capable of triggering inflammation. As there is currently no empirically derived agreement on therapeutic re-nourishment in AN, this review discusses how consideration of gut–brain interactions may be important for treatment regarding the determination of target weight, rapidity of weight gain, refeeding methods and composition of the diet which might all be of importance to improve long-term outcome of one of the most chronic psychiatric disorders of adolescence.

The neural correlates of movement intentions: a pilot study comparing hypnotic and simulated paralysis

The distinct feeling of wanting to act and thereby causing our own actions is crucial to our self-perception as free human agents. Disturbances of the link between intention and action occur in several disorders. Little is known, however, about the neural correlates of wanting or intending to act. To investigate these for simple voluntary movements, we used a paradigm involving hypnotic paralysis and functional magnetic resonance imaging. Eight healthy women were instructed to sequentially perform left and right hand movements during a normal condition, as well as during simulated weakness, simulated paralysis and hypnotic paralysis of the right hand. Right frontopolar cortex was selectively hypoactivated for attempted right hand movement during simulated paralysis while it was active in all other conditions. Since simulated paralysis was the only condition lacking an intention to move, the activation in frontopolar cortex might be related to the intention or volition to move.

Motivation to change and perceptions of the admission process with respect to outcome in adolescent anorexia nervosa

BackgroundIn patients with anorexia nervosa (AN), there is evidence that readiness to change is an important predictor of outcome with respect to weight gain and improvement in eating disorder psychopathology. In particular, young patients are characterized by a low level of motivation for recovery and perceive more coercion at hospitalization. Thus, a better understanding of the variables that influence readiness to change and perception of the admission process in adolescent AN may help to support patients in initiating change and staying motivated for treatment.MethodsIn 40 adolescent patients diagnosed with AN according to DSM-IV criteria, we assessed in a prospective clinical cohort study the motivation to change using the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ) at admission to inpatient treatment, in week 9 after admission and at discharge. Additional variables were assessed, including depressive symptoms (Beck Depression Inventory, BDI), eating disorder-specific psychopathology (Eating Disorder Inventory, EDI-2), body mass index (BMI) and the percentage of expected body weight (%EBW). The patients’ perceptions of the admission process and their perceived need for hospitalization were assessed using a self-report scale developed by Guarda et al. (2007).ResultsYounger patients perceived more coercion than older patients did. Low %EBW and more severe eating disorder-specific psychopathology were associated with a greater perceived need for hospitalization. Moreover, low %EBW at admission and a longer duration of illness were accompanied by a greater motivation to change at admission, whereas more severe eating disorder psychopathology was associated with a low motivation to change. The motivation to change increased significantly between admission and discharge. Patients with a greater motivation to change at admission exhibited a higher weekly weight gain during treatment but did not show better outcome in eating disorder-specific psychopathology and depression.ConclusionsMotivation to change is an important predictor of short-term outcome with respect to weight gain trajectory during treatment of adolescent AN. As patients with a higher BMI at admission and those with more severe eating disorder-specific symptoms seem to be less motivated to change, the crucial issue of motivation to change should be addressed with these patients during the therapeutic process.

Reduced astrocyte density underlying brain volume reduction in activity-based anorexia rats

Abstract Objectives: Severe grey and white matter volume reductions were found in patients with anorexia nervosa (AN) that were linked to neuropsychological deficits while their underlying pathophysiology remains unclear. For the first time, we analysed the cellular basis of brain volume changes in an animal model (activity-based anorexia, ABA). Methods: Female rats had 24 h/day running wheel access and received reduced food intake until a 25% weight reduction was reached and maintained for 2 weeks. Results: In ABA rats, the volumes of the cerebral cortex and corpus callosum were significantly reduced compared to controls by 6% and 9%, respectively. The number of GFAP-positive astrocytes in these regions decreased by 39% and 23%, total astrocyte-covered area by 83% and 63%. In neurons no changes were observed. The findings were complemented by a 60% and 49% reduction in astrocyte (GFAP) mRNA expression. Conclusions: Volumetric brain changes in ABA animals mirror those in human AN patients. These alterations are associated with a reduction of GFAP-positive astrocytes as well as GFAP expression. Reduced astrocyte functioning could help explain neuronal dysfunctions leading to symptoms of rigidity and impaired learning. Astrocyte loss could constitute a new research target for understanding and treating semi-starvation and AN.