Disrupted longitudinal restoration of brain connectivity during weight normalization in severe anorexia nervosa.

Altered intrinsic brain connectivity of patients with anorexia nervosa has been observed in the acute phase of the disorder, but it remains unclear to what extent these alterations recover during weight normalization. In this study, we used functional imaging data from three time points to probe longitudinal changes in intrinsic connectivity patterns in patients with severe anorexia nervosa (BMI ≤ 15.5 kg/m2) over the course of weight normalization. At three distinct stages of inpatient treatment, we examined resting-state functional connectivity in 27 women with severe anorexia nervosa and 40 closely matched healthy controls. Using network-based statistics and graph-theoretic measures, we examined differences in global network strength, subnetworks with altered intrinsic connectivity, and global network topology. Patients with severe anorexia nervosa showed weakened intrinsic connectivity and altered network topology which did not recover during treatment. The persistent disruption of brain networks suggests sustained alterations of information processing in weight-recovered severe anorexia nervosa.

Does local cerebellar volume predict treatment success in anorexia nervosa?

Anorexia nervosa (AN) is difficult to treat with up to half of patients failing to gain weight during treatment. Neurobiological factors predicting treatment response in AN are poorly understood. In this longitudinal study, we aimed to identify morphological characteristics in the grey matter which predict treatment success in patients with AN. Fifty patients with severe AN participated in an eating disorder-specific inpatient treatment. On admission, T1-weighted magnetic resonance images were acquired from all patients. Half of the patients successfully gained weight, reaching a body-mass index ≥ 17.5 kg/m2. Using voxel-based morphometry, local grey matter volumes were compared between the two groups of patients who gained weight and those who did not. This approach allowed us to identify anatomical characteristics which predict treatment success in terms of post-treatment weight status. Patients who did not reach the weight threshold at discharge had a smaller volume in the right cerebellar crus I at the time of admission. In this group, smaller volume was associated with a greater alexithymia score. The findings suggest that a trophic state within the cerebellum before treatment might be prognostic for treatment success. Consistent with previous reports, this result further substantiates the possible role of the cerebellum in the psychopathology of AN.

Age influences structural brain restoration during weight gain therapy in anorexia nervosa.

Neuroimaging studies on anorexia nervosa (AN) have consistently reported globally reduced gray matter in patients with acute AN. While first studies on adolescent AN patients provide evidence for the reversibility of these impairments after weight gain, longitudinal studies with detailed regional analysis for adult AN patients are lacking and factors associated with brain restitution are poorly understood. We investigated structural changes in anorexia nervosa using T1-weighted magnetic resonance images with surface-based morphometry. The sample consisted of 26 adult women with severe AN and 30 healthy controls. The longitudinal design comprised three time points, capturing the course of weight-restoration therapy in AN patients at distinct stages of weight gain (BMI ≤ 15.5 kg/m2; 15.5 < BMI < 17.5 kg/m2; BMI ≥ 17.5 kg/m2). Compared to controls, AN patients showed globally decreased cortical thickness and subcortical volumes at baseline. Linear mixed effect models revealed the reversibility of these alterations, with brain restoration being most pronounced during the first half of treatment. The restoration of cortical thickness of AN patients negatively correlated with age, but not duration of illness. After weight restoration, residual group differences of cortical thickness remained in the superior frontal cortex. These findings indicate that structural brain alterations of adult patients with severe AN recuperate independently of the duration of illness during weight-restoration therapy. The temporal pattern of brain restoration suggests a decrease in restoration rate over the course of treatment, with patients' age as a strong predictor of brain restitution, possibly reflecting decreases of brain plasticity as patients grow older.

How fat will it make me? Estimation of weight gain in anorexia nervosa.

This study investigates the subjective estimation of weight gain in patients with anorexia nervosa (AN) when being confronted with food cues both in a general (self-unrelated) and in an intent-to-eat (self-related) condition. Looking at the presentation of different snack pictures with different nutrition values (high-low calories), AN patients (N = 24) and age-matched healthy women (N = 27) estimated the weight gain when they imagined eating the presented portions of snack pictures once a day in addition to the normal daily nutrition in the following two conditions: 1) a general condition without specific additional instruction, 2) an intent-to-eat condition, in which they were instructed to imagine that they would eat the snack themselves. Compared to healthy women, patients with AN estimated a higher weight gain only in the intent-to-eat condition, i.e. when they imagined eating the snacks themselves, but not in the general, not self-related condition. In the patient group, mean estimations of weight gain were associated with the "drive for thinness". This study suggests cognitive abnormalities related to the effects of food intake on the weight gain in AN, and that these cognitive anomalies could be related to the fear of gaining weight, one central symptom of AN. It appears that the self-reflective disturbed cognition, rather than the general cognition, could be the main driver underlying anorexia and that the overestimation of the energetic content of food is related to the drive for thinness.

Fornix Under Water? Ventricular Enlargement Biases Forniceal Diffusion Magnetic Resonance Imaging Indices in Anorexia Nervosa.

BACKGROUND: Acute anorexia nervosa (AN) is characterized by reduced brain mass and corresponding increased sulcal and ventricular cerebrospinal fluid. Recent studies of white matter using diffusion tensor imaging consistently identified alterations in the fornix, such as reduced fractional anisotropy (FA). However, because the fornix penetrates the ventricles, it is prone to cerebrospinal fluid-induced partial volume effects that interfere with a valid assessment of FA. We investigated the hypothesis that in the acute stage of AN, FA of the fornix is markedly affected by ventricular volumes. METHODS: First, using diffusion tensor imaging data we established the inverse associations between forniceal FA and volumes of the third and lateral ventricles in a prestudy with 32 healthy subjects to demonstrate the strength of ventricular influence on forniceal FA independent of AN. Second, we investigated a sample of 25 acute AN patients and 25 healthy control subjects. RESULTS: Using ventricular volumes as covariates markedly reduced the group effect of forniceal FA, even with tract-based spatial statistics focusing only on the center of the fornix. In addition, after correcting for free water on voxel level, the group differences in forniceal FA between AN patients and controls disappeared completely. CONCLUSIONS: It is unlikely that microstructural changes affecting FA occurred in the fornix of AN patients. Previously identified alterations in acute AN may have been biased by partial volume effects and the proposed central role of this structure in the pathophysiology may need to be reconsidered. Future studies on white matter alterations in AN should carefully deal with partial volume effects.

Musician's dystonia is highly task specific: no strong evidence for everyday fine motor deficits in patients.

OBJECTIVES: 1) To examine the fine motor skills used everyday by patients suffering from musician's dystonia (MD) in the upper limb in order to verify whether MD is task-specific; and 2) to compare the affected and non-affected hands of MD musicians vs healthy musicians in performance of these tasks in order to clarify whether dystonic symptoms can be found in the non-affected side of MD patients. BACKGROUND: MD is typically considered to be focal and task specific, but patients often report impairment in everyday life activities. Furthermore, in the course of MD, about 15% of patients complain of dystonic symptoms in other parts of the body. METHODS: Twenty-seven musicians affected by MD and 27 healthy musicians were studied using 1) the Motor Performance Test Series, 2) a kinematic analysis of handwriting, and 3) an assessment of the grip force regulation while lifting and moving a manipulandum. RESULTS: Patients performed most fine motor tasks without any evidence of a deficit. Exclusively in the handwriting tasks (2), they exhibited fewer frequencies of the written trace and a prolonged overall writing time. CONCLUSION: MD is highly task specific and does not strongly affect other motor skills. The subtle deficits in handwriting may be explained as a consequence of a general psychological disposition rather than as compensatory mechanisms to avoid the appearance of dystonic symptoms. Furthermore, we did not find signs of multifocal motor deficits in the unaffected hands of MD patients.

Being in two minds: the neural basis of experiencing action crises in personal long-term goals.

Although the successful pursuit of long-term goals constitutes an essential prerequisite to personal development, health, and well-being, little research has been devoted to the understanding of its underlying neural processes. A critical phase in the pursuit of long-term goals is defined as an action crisis, conceptualized as the intra-psychic conflict between further goal pursuit and disengagement from the goal. In the present research, we applied an interdisciplinary (cognitive and neural) approach to the analysis of processes underlying the experience of an action crisis. In Study 1, a longitudinal field study, action crises in personal goals gave rise to an increased and unbiased (re)evaluation of the costs and benefits (i.e., rewards) of the goal. Study 2 was a magnetic resonance imaging study examining resting-state functional connectivity. The extent of experienced action crises was associated with enhanced fronto-accumbal connectivity signifying increased reward-related impact on prefrontal action control. Action crises, furthermore, mediated the relationship between a dispositional measure of effective goal pursuit (action orientation) and fronto-accumbal connectivity. The converging and complementary results from two methodologically different approaches advance the understanding of the neurobiology of personal long-term goals, especially with respect to the role of rewards in the context of goal-related conflicts.

Increased cortical thickness in a frontoparietal network in social anxiety disorder.

Social anxiety disorder (SAD) is the second leading anxiety disorder. On the functional neurobiological level, specific brain regions involved in the processing of anxiety-laden stimuli and in emotion regulation have been shown to be hyperactive and hyper-responsive in SAD such as amygdala, insula and orbito- and prefrontal cortex. On the level of brain structure, prior studies on anatomical differences in SAD resulted in mixed and partially contradictory findings. Based on previous functional and anatomical models of SAD, this study examined cortical thickness in structural magnetic resonance imaging data of 46 patients with SAD without comorbidities (except for depressed episode in one patient) compared with 46 matched healthy controls in a region of interest-analysis and in whole-brain. In a theory-driven ROI-analysis, cortical thickness was increased in SAD in left insula, right anterior cingulate and right temporal pole. Furthermore, the whole-brain analysis revealed increased thickness in right dorsolateral prefrontal and right parietal cortex. This study detected no regions of decreased cortical thickness or brain volume in SAD. From the perspective of brain networks, these findings are in line with prior functional differences in salience networks and frontoparietal networks associated with executive-controlling and attentional functions.

Axis-I comorbidity is linked to prospective instability of diagnoses within eating disorders.

BACKGROUND: Eating disorders (ED) are classified into Anorexia Nervosa, Bulimia Nervosa, and eating disorder not otherwise specified. Prospectively, the diagnostic instability within ED is high, but it is not clear which factors may account for this instability. So far, there is no evidence of whether psychiatric comorbidity may play a role in ED diagnostic crossover. We sought to determine possible influences of comorbidities of axis I and II on diagnostic crossover within ED. METHODS: Longitudinal data of 192 female patients were collected. All patients had a diagnosis of a current ED at study entry (baseline, T0). Diagnoses were re-established both 12 months (T1) and 30 months (T2) after T0. Comorbid psychiatric diagnoses were grouped into axis I and axis II according to DSM-IV. RESULTS: Patients with instable ED diagnoses had lifetime axis-I comorbidity more frequently than patients with stable ED diagnoses (χ2 = 4.74, df = 1, p < 0.05). Post-hoc exploratory tests suggested that the effect was mainly driven by affective disorders like major depression. There was no difference for axis-II comorbidity between stable and instable diagnostic profiles. CONCLUSIONS: Following previous reports of diagnostic crossover in ED, the present investigation points to an influence of a life-time psychiatric comorbidity, in particular of axis I, on follow-up diagnoses of ED. Comorbid affective disorders like major depression might facilitate a switching between clinical phenotypes. The understanding of mechanisms and causes of the symptoms fluctuation will be subject of future studies.

Evidence of frontotemporal structural hypoconnectivity in social anxiety disorder: A quantitative fiber tractography study.

Investigation of the brain's white matter fiber tracts in social anxiety disorder (SAD) may provide insight into the underlying pathophysiology. Because models of pathological anxiety posit altered frontolimbic interactions, the uncinate fasciculus (UF) connecting (orbito-) frontal and temporal areas including the amygdala is of particular interest. Microstructural alterations in parts of the UF have been reported previously, whereas examination of the UF as discrete fiber tract with regard to more large-scale properties is still lacking. Diffusion tensor imaging was applied in 25 patients with generalized SAD and 25 healthy control subjects matched by age and gender. By means of fiber tractography, the UF was reconstructed for each participant. The inferior fronto-occipital fasciculus (IFOF), originating from the frontal cortex similarly to the UF, was additionally included as control tract. Volume and fractional anisotropy (FA) were compared between the groups for both tracts. Volume of left and right UF was reduced in patients with SAD, reaching statistical significance for the left UF. Bilateral IFOF volume was not different between groups. A similar pattern was observed for FA. Reduced volume of the left UF in SAD fits well into pathophysiological models of anxiety, as it suggests deficient structural connectivity between higher-level control areas in the orbitofrontal cortex and more basal limbic areas like the amygdala. The results point to a specific role of the left UF with regard to altered white matter volume in SAD. However, results should be replicated and functional correlates of altered UF volume be determined in future studies.

Resting-state functional and structural connectivity within an insula-amygdala route specifically index state and trait anxiety.

BACKGROUND: Conjoint activity of the insula and amygdala has frequently been reported during emotional stimulation in general and in anxiety-related contexts in particular. However, direct connectivity between the insula and amygdala in this framework has received little attention so far. Studying whether inter-individual differences in anxiety reflect variation in insula-amygdala connectivity is a way to push forward the understanding of network-related aspects underlying anxious behavior. METHODS: To investigate functional and structural connectivity, we applied resting-state functional magnetic resonance imaging and diffusion tensor imaging in a group of 32 healthy subjects. Specific measures of connectivity between subregions of the insula and amygdala were related to subjects' anxiety levels. RESULTS: Resting-state functional connectivity between the anterior insula and the basolateral amygdala was strongly related to state anxiety, explaining 40% of behavioral variance across subjects. This was substantiated by applying tractography, yielding a relationship between trait anxiety and axial diffusivity for a direct pathway between anterior insula and basolateral amygdala. CONCLUSIONS: Our results indicate that anterior insula and basolateral amygdala constitute a network part that is prominently linked to anxiety. Within this route, state and trait behavioral impacts seem to be specifically linked to dynamic functional and more static structural neural aspects, respectively. Insula-amygdala resting-state functional connectivity can be assessed in an easy and straightforward way and has high potential to serve as a biomarker for anxiety.

Musician's cramp as manifestation of maladaptive brain plasticity: arguments from instrumental differences.

Musician's cramp is a task-specific movement disorder that presents itself as muscular incoordination or loss of voluntary motor control of extensively trained movements while a musician is playing the instrument. It is characterized by task specificity and gender bias, affecting significantly more males than females. The etiology is multifaceted: a combination of a genetic predisposition, termed endophenotype, and behavioral triggering factors being the leading features for the manifestation of the disorder. We present epidemiological data from 591 musician patients from our outpatient clinic demonstrating an influence of fine-motor requirements on the manifestation of dystonia. Brass, guitar, and woodwind players were at greater risk than other instrumentalists. High temporospatial precision of movement patterns, synchronous demands on tonic and phasic muscular activation, in combination with fine-motor burdens of using the dominant hand in daily life activities, constitute as triggering factors for the disorder and may explain why different body parts are affected.

Volumetric associations between uncinate fasciculus, amygdala, and trait anxiety.

BACKGROUND: Recent investigations of white matter (WM) connectivity suggest an important role of the uncinate fasciculus (UF), connecting anterior temporal areas including the amygdala with prefrontal-/orbitofrontal cortices, for anxiety-related processes. Volume of the UF, however, has rarely been investigated, but may be an important measure of structural connectivity underlying limbic neuronal circuits associated with anxiety. Since UF volumetric measures are newly applied measures, it is necessary to cross-validate them using further neural and behavioral indicators of anxiety. RESULTS: In a group of 32 subjects not reporting any history of psychiatric disorders, we identified a negative correlation between left UF volume and trait anxiety, a finding that is in line with previous results. On the other hand, volume of the left amygdala, which is strongly connected with the UF, was positively correlated with trait anxiety. In addition, volumes of the left UF and left amygdala were inversely associated. CONCLUSIONS: The present study emphasizes the role of the left UF as candidate WM fiber bundle associated with anxiety-related processes and suggests that fiber bundle volume is a WM measure of particular interest. Moreover, these results substantiate the structural relatedness of UF and amygdala by a non-invasive imaging method. The UF-amygdala complex may be pivotal for the control of trait anxiety.

Single-session tDCS-supported retraining does not improve fine motor control in musician's dystonia.

BACKGROUND: Focal dystonia in musicians (MD) is a task-specific movement disorder with a loss of voluntary motor control during instrumental playing. Defective inhibition on different levels of the central nervous system is involved in the pathophysiology. Sensorimotor retraining is a therapeutic approach to MD and aims to establish non-dystonic movements. Transcranial direct current stimulation (tDCS) modulates cortical excitability and alters motor performance. In this study, tDCS of the motor cortex was expected to assist retraining at the instrument. METHODS: Nine professional pianists suffering from MD were included in a placebo-controlled double-blinded study. Retraining consisted of slow, voluntarily controlled movements on the piano and was combined with tDCS. Patients were treated with three stimulation protocols: anodal tDCS, cathodal tDCS and placebo stimulation. RESULTS: No beneficial effects of single-session tDCS-supported sensorimotor retraining on fine motor control in pianists with MD were found in all three conditions. CONCLUSIONS: The main cause of the negative result of this study may be the short intervention time. One retraining session with a duration of 20 min seems not sufficient to improve symptoms of MD. Additionally, a single tDCS session might not be sufficient to modify sensorimotor learning of a highly skilled task in musicians with dystonia.

White matter alterations in social anxiety disorder.

White matter architecture in patients with social anxiety disorder (SAD) has rarely been investigated, but may yield insights with respect to altered structural brain connectivity. Initial evidence points to alterations in the uncinate fasciculus (UF). We applied diffusion tensor imaging in 25 patients with SAD and 25 matched healthy subjects. Whole-brain fractional anisotropy (FA) maps were used for group comparison and voxel-wise correlation with psychometric and clinical measures. Additionally, a region-of-interest analysis of the UF was performed. Patients with SAD had reduced FA compared to healthy subjects in or near the left UF and the left superior longitudinal fasciculus. There were no regions with increased FA in SAD. In the region-of-interest analysis, a negative correlation between FA and trait anxiety was identified in the left and right UF in patients, but not in healthy subjects. No correlations with social anxiety scores were observed. The present study partially confirms previous results pointing to frontal WM alterations in or near the UF in patients with SAD. SAD-specific dimensional associations of FA with trait anxiety might reflect general pathological and/or compensatory mechanisms as a function of symptom severity in patients. Future studies should disentangle in which way the identified WM alterations match functional alterations.