Frontostriatal functional connectivity correlates with repetitive behaviour across autism spectrum disorder and obsessive-compulsive disorder.

BACKGROUND: Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) are neurodevelopmental disorders with considerable overlap in terms of their defining symptoms of compulsivity/repetitive behaviour. Little is known about the extent to which ASD and OCD have common versus distinct neural correlates of compulsivity. Previous research points to potentially common dysfunction in frontostriatal connectivity, but direct comparisons in one study are lacking. Here, we assessed frontostriatal resting-state functional connectivity in youth with ASD or OCD, and healthy controls. In addition, we applied a cross-disorder approach to examine whether repetitive behaviour across ASD and OCD has common neural substrates. METHODS: A sample of 78 children and adolescents aged 8-16 years was used (ASD n = 24; OCD n = 25; healthy controls n = 29), originating from the multicentre study COMPULS. We tested whether diagnostic group, repetitive behaviour (measured with the Repetitive Behavior Scale-Revised) or their interaction was associated with resting-state functional connectivity of striatal seed regions. RESULTS: No diagnosis-specific differences were detected. The cross-disorder analysis, on the other hand, showed that increased functional connectivity between the left nucleus accumbens (NAcc) and a cluster in the right premotor cortex/middle frontal gyrus was related to more severe symptoms of repetitive behaviour. CONCLUSIONS: We demonstrate the fruitfulness of applying a cross-disorder approach to investigate the neural underpinnings of compulsivity/repetitive behaviour, by revealing a shared alteration in functional connectivity in ASD and OCD. We argue that this alteration might reflect aberrant reward or motivational processing of the NAcc with excessive connectivity to the premotor cortex implementing learned action patterns.

Evidence for a Sex-Dependent MAOA× Childhood Stress Interaction in the Neural Circuitry of Aggression.

Converging evidence emphasizes the role of an interaction between monoamine oxidase A (MAOA) genotype, environmental adversity, and sex in the pathophysiology of aggression. The present study aimed to clarify the impact of this interaction on neural activity in aggression-related brain systems. Functional magnetic resonance imaging was performed in 125 healthy adults from a high-risk community sample followed since birth. DNA was genotyped for the MAOA-VNTR (variable number of tandem repeats). Exposure to childhood life stress (CLS) between the ages of 4 and 11 years was assessed using a standardized parent interview, aggression by the Youth/Young Adult Self-Report between the ages of 15 and 25 years, and the VIRA-R (Vragenlijst Instrumentele En Reactieve Agressie) at the age of 15 years. Significant interactions were obtained between MAOA genotype, CLS, and sex relating to amygdala, hippocampus, and anterior cingulate cortex (ACC) response, respectively. Activity in the amygdala and hippocampus during emotional face-matching increased with the level of CLS in male MAOA-L, while decreasing in male MAOA-H, with the reverse pattern present in females. Findings in the opposite direction in the ACC during a flanker NoGo task suggested that increased emotional activity coincided with decreased inhibitory control. Moreover, increasing amygdala activity was associated with higher Y(A)SR aggression in male MAOA-L and female MAOA-H carriers. Likewise, a significant association between amygdala activity and reactive aggression was detected in female MAOA-H carriers. The results point to a moderating role of sex in the MAOA× CLS interaction for intermediate phenotypes of emotional and inhibitory processing, suggesting a possible mechanism in conferring susceptibility to violence-related disorders.

Association between pubertal stage at first drink and neural reward processing in early adulthood.

Puberty is a critical time period during human development. It is characterized by high levels of risk-taking behavior, such as increased alcohol consumption, and is accompanied by various neurobiological changes. Recent studies in animals and humans have revealed that the pubertal stage at first drink (PSFD) significantly impacts drinking behavior in adulthood. Moreover, neuronal alterations of the dopaminergic reward system have been associated with alcohol abuse or addiction. This study aimed to clarify the impact of PSFD on neuronal characteristics of reward processing linked to alcohol-related problems. One hundred sixty-eight healthy young adults from a prospective study covering 25 years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. PSFD was determined according to the age at menarche or Tanner stage of pubertal development, respectively. Alcohol-related problems in early adulthood were assessed with the Alcohol Use Disorder Identification Test (AUDIT). During reward anticipation, decreased fMRI activation of the frontal cortex and increased preparatory EEG activity (contingent negative variation) occurred with pubertal compared to postpubertal first alcohol intake. Moreover, alcohol-related problems during early adulthood were increased in pubertal compared to postpubertal beginners, which was mediated by neuronal activation of the right medial frontal gyrus. At reward delivery, increased fMRI activation of the left caudate and higher feedback-related EEG negativity were detected in pubertal compared to postpubertal beginners. Together with animal findings, these results implicate PSFD as a potential modulator of psychopathology, involving altered reward anticipation. Both PSFD timing and reward processing might thus be potential targets for early prevention and intervention.

Interaction between COMT Val(158)Met polymorphism and childhood adversity affects reward processing in adulthood.

BACKGROUND: Accumulating evidence suggests that altered dopamine transmission may increase the risk of mental disorders such as ADHD, schizophrenia or depression, possibly mediated by reward system dysfunction. This study aimed to clarify the impact of the COMT Val(158)Met polymorphism in interaction with environmental variation (G×E) on neuronal activity during reward processing. METHODS: 168 healthy young adults from a prospective study conducted over 25years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. DNA was genotyped for COMT, and childhood family adversity (CFA) up to age 11 was assessed by a standardized parent interview. RESULTS: At reward delivery, a G×E revealed that fMRI activation for win vs. no-win trials in reward-related regions increased with the level of CFA in Met homozygotes as compared to Val/Met heterozygotes and Val homozygotes, who showed no significant effect. During the anticipation of monetary vs. verbal rewards, activation decreased with the level of CFA, which was also observed for EEG, in which the CNV declined with the level of CFA. CONCLUSIONS: These results identify convergent genetic and environmental effects on reward processing in a prospective study. Moreover, G×E effects during reward delivery suggest that stress during childhood is associated with higher reward sensitivity and reduced efficiency in processing rewarding stimuli in genetically at-risk individuals. Together with previous evidence, these results begin to define a specific system mediating interacting effects of early environmental and genetic risk factors, which may be targeted by early intervention and prevention.

Frequency-specific coupling between trial-to-trial fluctuations of neural responses and response-time variability.

We assessed intra-individual variability of response times (RT) and single-trial P3 amplitudes following targets in healthy adults during a Flanker/NO-GO task. RT variability and variability of the neural responses coupled at the faster frequencies examined (0.07-0.17 Hz) at Pz, the target-P3 maxima, despite non-significant associations for overall variability (standard deviation, SD). Frequency-specific patterns of variability in the single-trial P3 may help to understand the neurophysiology of RT variability and its explanatory models of attention allocation deficits beyond intra-individual variability summary indices such as SD.

Simultaneous EEG and fMRI reveals a causally connected subcortical-cortical network during reward anticipation.

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been used to study the neural correlates of reward anticipation, but the interrelation of EEG and fMRI measures remains unknown. The goal of the present study was to investigate this relationship in response to a well established reward anticipation paradigm using simultaneous EEG-fMRI recording in healthy human subjects. Analysis of causal interactions between the thalamus (THAL), ventral-striatum (VS), and supplementary motor area (SMA), using both mediator analysis and dynamic causal modeling, revealed that (1) THAL fMRI blood oxygenation level-dependent (BOLD) activity is mediating intermodal correlations between the EEG contingent negative variation (CNV) signal and the fMRI BOLD signal in SMA and VS, (2) the underlying causal connectivity network consists of top-down regulation from SMA to VS and SMA to THAL along with an excitatory information flow through a THAL→VS→SMA route during reward anticipation, and (3) the EEG CNV signal is best predicted by a combination of THAL fMRI BOLD response and strength of top-down regulation from SMA to VS and SMA to THAL. Collectively, these findings represent a likely neurobiological mechanism mapping a primarily subcortical process, i.e., reward anticipation, onto a cortical signature.

Sequential inhibitory control processes assessed through simultaneous EEG-fMRI.

Inhibitory response control has been extensively investigated in both electrophysiological (ERP) and hemodynamic (fMRI) studies. However, very few multimodal results address the coupling of these inhibition markers. In fMRI, response inhibition has been most consistently linked to activation of the anterior insula and inferior frontal cortex (IFC), often also the anterior cingulate cortex (ACC). ERP work has established increased N2 and P3 amplitudes during NoGo compared to Go conditions in most studies. Previous simultaneous EEG-fMRI imaging reported association of the N2/P3 complex with activation of areas like the anterior midcingulate cortex (aMCC) and anterior insula. In this study we investigated inhibitory control in 23 healthy young adults (mean age=24.7, n=17 for EEG during fMRI) using a combined Flanker/NoGo task during simultaneous EEG and fMRI recording. Separate fMRI and ERP analysis yielded higher activation in the anterior insula, IFG and ACC as well as increased N2 and P3 amplitudes during NoGo trials in accordance with the literature. Combined analysis modelling sequential N2 and P3 effects through joint parametric modulation revealed correlation of higher N2 amplitude with deactivation in parts of the default mode network (DMN) and the cingulate motor area (CMA) as well as correlation of higher central P3 amplitude with activation of the left anterior insula, IFG and posterior cingulate. The EEG-fMRI results resolve the localizations of these sequential activations. They suggest a general role for allocation of attentional resources and motor inhibition for N2 and link memory recollection and internal reflection to P3 amplitude, in addition to previously described response inhibition as reflected by the anterior insula.

Effects of normal aging and SCN1A risk-gene expression on brain metabolites: evidence for an association between SCN1A and myo-inositol.

Previously reported MRS findings in the aging brain include lower N-acetylaspartate (NAA) and higher myo-inositol (mI), total creatine (Cr) and choline-containing compound (Cho) concentrations. Alterations in the sodium channel voltage gated type I, alpha subunit SCN1A variant rs10930201 have been reported to be associated with several neurological disorders with cognitive deficits. MRS studies in SCN1A-related diseases have reported striking differences in the mI concentrations between patients and controls. In a study on 'healthy aging', we investigated metabolite spectra in a sample of 83 healthy volunteers and determined their age dependence. We also investigated a potential link between SCN1A and mI. We observed a significantly negative association of NAA (p = 0.004) and significantly positive associations of mI (p ≤ 0.001), Cr (p ≤ 0.001) and Cho (p = 0.034) with age in frontal white matter. The linear association of Cho ends at the age of about 50 years and is followed by an inverted 'U'-shaped curve. Further, mI was higher in C allele carriers of the SCN1A variant rs10930201. Our results corroborated the age-related changes in metabolite concentrations, and found evidence for a link between SCN1A and frontal white matter mI in healthy subjects.

Accelerated sample preparation and formation of astragaloside IV in Astragali Radix.

Abstract Context: Astragali Radix (Huangqi; Astragalus mongholicus BUNGE, Fabaceae) is used in herbal medicinal products as well as in many food supplements. In traditional Chinese medicine, the roots are used for its Qi tonifying, immunostimulant, cardioprotective, hepatoprotective and hypoglycemic effects. Objective: Astragaloside IV (AGS-IV), a cycloartane-type triterpene glycoside is used as a marker compound for the quality control of Astragali Radix in various pharmacopoeias. Materials and methods: In this study, we analyzed the content of AGS-IV and other astragalosides in various commercial samples of Huangqi by reversed-phase HPLC using evaporative light scattering detection. Results: The analyses revealed that AGS-IV is formed during sample preparation from acylated astragalosides like astragaloside I and astragaloside II, when using the assay method of the European Pharmacopoeia. Discussion and conclusion: For consistent assay results, the extraction methods of the pharmacopoeias should be re-evaluated and optimized. Alternatively, the hydrolysis by ammonia could be omitted and the genuine compounds like astragaloside I, II and malonyl-AGS-I could be considered for the quality control of Astragali Radix.

ITF-2 is disrupted via allelic loss of chromosome 18q21, and ITF-2B expression is lost at the adenoma-carcinoma transition.

BACKGROUND & AIMS: The ubiquitously expressed basic helix-loop-helix transcription factor ITF-2B has an important role in differentiation processes, and its transcription is regulated by beta-catenin. The ITF-2 gene is located in the chromosomal region 18q21; allelic loss of this locus occurs in 70% of colorectal cancers. We analyzed the expression, regulation, and function of ITF-2B in colorectal carcinogenesis. METHODS: The loss-of-heterozygosity (LOH) status of 18q21 and expression of ITF-2B were studied in colorectal carcinomas using polymerase chain reaction-based methods and immunohistochemistry. The biologic effects of ITF-2B were studied in colorectal cancer cells. Reporter gene assays and chromatin immunoprecipitation were utilized to analyze effects of ITF-2B on gene transcription. RESULTS: ITF-2B is strongly expressed in colon adenomas but frequently down-regulated in carcinomas because of LOH at 18q21. ITF-2B induces cell cycle arrest and regulates the expression of p21(Cip1) via newly identified E-boxes in the CDKN1A gene, independently of p53. Loss of ITF-2B expression correlates with loss of p21(Cip1) expression in primary colon carcinomas. CONCLUSIONS: Accumulation of mutations and allelic losses are driving forces of colorectal carcinogenesis. ITF-2B, which is up-regulated during early colorectal carcinogenesis because of loss of adenomatous polyposis coli, is a target for LOH on chromosome 18q, along with deleted in colorectal carcinoma and Smad4. This finding, along with the fact that ITF-2B is a regulator of the key cell cycle inhibitor p21(Cip1), indicates that ITF-2B is a tumor suppressor that has an important function at the adenoma to carcinoma transition.

The impact of successful learning of self-regulation on reward processing in children with ADHD using fMRI.

Neurofeedback (NF) is a non-pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) that is targeting self-regulation, is efficacious when standard protocols are used and induces partly specific neurophysiological changes in the inhibitory network. However, its effects on reward processing, which is also considered an important aspect of ADHD and has been linked to neurophysiological deficits, remain unknown. Children with ADHD (N = 15, mean age 11.8, SD 1.52) were randomly assigned to either slow cortical potential NF (n = 8) or EMG biofeedback control training (n = 7) and received 20 sessions of training under comparable conditions. Learning was defined as the slope of successful training runs across all transfer sessions. Whole brain analysis, region-of-interest analysis of anticipatory ventral striatal (VS) activation, and analysis of behavioral data were performed. Clinically, the NF group improved more than the EMG group. Whole brain analysis indicated increased activation in the left superior frontal gyrus in the control group only, and in medial prefrontal cortex and dorsolateral prefrontal gyrus (DLPFC) after treatment across all groups. Only successful learners of self-regulation (n = 8) showed increased left inferior frontal gyrus and DLPFC activation after treatment. Left VS activation was increased after treatment and showed a significant time*medication-status interaction. Specific treatment effects were found in left frontal regions for the control treatment and successful learners. Also, unmedicated participants, irrespective of treatment type or successful learning, showed treatment-induced improvement in reward processing. The results suggest no prominent specific effect of NF on reward processing. However, cautious interpretation is warranted due to the small sample.

Neural network-based alterations during repetitive heat pain stimulation in major depression.

The current study aimed to identify alterations in brain activation and connectivity related to nociceptive processing and pain sensitization in major depressive disorder (MDD), using repetitive heat pain stimulation during functional magnetic resonance imaging (fMRI) in 37 MDD patients and 33 healthy controls. Regional activation did not differ between groups, but functional connectivity was significantly decreased in MDD in a neural network connecting frontal, temporal and occipital areas (family-wise error-corrected pFWE = 0.045). Supporting analyses suggested a significant association between network connectivity and trait neuroticism (p = 0.007) but not with the clinical state or familiar risk of MDD (all p values > 0.13). Our data relate a network-based phenotype for altered pain processing and antinociceptive control to MDD and encourage future studies on the shared intermediate neural psychological risk architecture of MDD and chronic pain.

No evidence of differences in cognitive control in children with autism spectrum disorder or obsessive-compulsive disorder: An fMRI study.

Repetitive behaviors are among the core symptoms of both Autism Spectrum Disorder (ASD) and Obsessive-Compulsive Disorder (OCD) and are thought to be associated with impairments in cognitive control. However, it is still unknown how deficits in cognitive control and associated neural circuitry relate to the quality or severity of repetitive behavior in children with these disorders. Therefore, we investigated the behavioral and neural correlates of cognitive control using a modified stop-signal task in a multicenter study of children (aged 8-12 years) with ASD, OCD and typically developing (TD) children (N = 95). As both ASD and OCD have high levels of comorbidity with Attention Deficit/Hyperactivity Disorder (ADHD), we did an exploratory analysis addressing ADHD-symptoms. We found that children with ASD and OCD did not show deficits in cognitive control or changes in brain activity in task-relevant neural networks when compared to TD children. However, increased activity in prefrontal brain areas was associated with increased symptoms of comorbid ADHD. As such, this study does not support differences in cognitive control or associated neural circuitry in children with ASD and OCD, but rather suggests that changes in cognitive control in these disorders may be related to symptoms of comorbid ADHD.

Neurofeedback Training Effects on Inhibitory Brain Activation in ADHD: A Matter of Learning?

Neurofeedback training (NF) is a promising non-pharmacological treatment for ADHD that has been associated with improvement of attention-deficit/hyperactivity disorder (ADHD)-related symptoms as well as changes in electrophysiological measures. However, the functional localization of neural changes following NF compared to an active control condition, and of successful learning during training (considered to be the critical mechanism for improvement), remains largely unstudied. Children with ADHD (N=16, mean age: 11.81, SD: 1.47) were randomly assigned to either slow cortical potential (SCP, n=8) based NF or biofeedback control training (electromyogram feedback, n=8) and performed a combined Flanker/NoGo task pre- and post-training. Effects of NF, compared to the active control, and of learning in transfer trials (approximating successful transfer to everyday life) were examined with respect to clinical outcome and functional magnetic resonance imaging (fMRI) changes during inhibitory control. After 20 sessions of training, children in the NF group presented reduced ADHD symptoms and increased activation in areas associated with inhibitory control compared to baseline. Subjects who were successful learners (n=9) also showed increased activation in an extensive inhibitory network irrespective of the type of training. Activation increased in an extensive inhibitory network following NF training, and following successful learning through NF and control biofeedback. Although this study was only powered to detect large effects and clearly requires replication in larger samples, the results suggest a crucial role for learning effects in biofeedback trainings.

Fronto-Striatal Glutamate in Autism Spectrum Disorder and Obsessive Compulsive Disorder.

This corrects the article DOI: 10.1038/npp.2016.260.

Fronto-Striatal Glutamate in Autism Spectrum Disorder and Obsessive Compulsive Disorder.

Autism spectrum disorders (ASDs) and obsessive compulsive disorder (OCD) are often comorbid with the overlap based on compulsive behaviors. Although previous studies suggest glutamatergic deficits in fronto-striatal brain areas in both disorders, this is the first study to directly compare the glutamate concentrations across the two disorders with those in healthy control participants using both categorical and dimensional approaches. In the current multi-center study (four centers), we used proton magnetic resonance spectroscopy in 51 children with ASD, 29 with OCD, and 53 healthy controls (aged 8-13 years) to investigate glutamate (Glu) concentrations in two regions of the fronto-striatal circuit: midline anterior cingulate cortex (ACC) and left dorsal striatum. Spectra were processed with Linear Combination Model. Group comparisons were performed with one-way analyses of variance including sex, medication use, and scanner site as covariates. In addition, a dimensional analysis was performed, linking glutamate with a continuous measure of compulsivity across disorders. There was a main group effect for ACC glutamate (p=0.019). Contrast analyses showed increased glutamate both in children with ASD and OCD compared with controls (p=0.007), but no differences between the two disorders (p=0.770). Dimensional analyses revealed a positive correlation between compulsive behavior (measured with the Repetitive Behavior Scale) and ACC glutamate (rho=0.24, p=0.03). These findings were robust across sites. No differences were found in the striatum. The current findings confirm overlap between ASD and OCD in terms of glutamate involvement. Glutamate concentration in ACC seems to be associated with the severity of compulsive behavior.

What supports students' education in the operating room? A focus group study including students' and surgeons' views.

BACKGROUND AND METHODS: We conducted a focus group analysis with students and surgeons on factors which influence medical school students' education in the operating room (OR). The interviews were analyzed using grounded theory. RESULTS: The analysis resulted in 18 detailed and easily applyable themes, which were grouped into the four categories: "Students' preparation and organizational aspects", "Learning objectives", "Educational strategies for the teacher", and "Social-environmental aspects". CONCLUSION: By including students and surgeons, we were able to extend existing knowledge and enable better understanding of factors influencing teaching in the OR.

Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume.

Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective self-report (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. The present results point to a functional involvement of FKBP5 in intermediate phenotypes associated with emotional processing, suggesting a possible mechanism for this gene in conferring susceptibility to stress-related disorders.

The long-term impact of early life poverty on orbitofrontal cortex volume in adulthood: results from a prospective study over 25 years.

Converging evidence has highlighted the association between poverty and conduct disorder (CD) without specifying neurobiological pathways. Neuroimaging research has emphasized structural and functional alterations in the orbitofrontal cortex (OFC) as one key mechanism underlying this disorder. The present study aimed to clarify the long-term influence of early poverty on OFC volume and its association with CD symptoms in healthy participants of an epidemiological cohort study followed since birth. At age 25 years, voxel-based morphometry was applied to study brain volume differences. Poverty (0=non-exposed (N=134), 1=exposed (N=33)) and smoking during pregnancy were determined using a standardized parent interview, and information on maternal responsiveness was derived from videotaped mother-infant interactions at the age of 3 months. CD symptoms were assessed by diagnostic interview from 8 to 19 years of age. Information on life stress was acquired at each assessment and childhood maltreatment was measured using retrospective self-report at the age of 23 years. Analyses were adjusted for sex, parental psychopathology and delinquency, obstetric adversity, parental education, and current poverty. Individuals exposed to early life poverty exhibited a lower OFC volume. Moreover, we replicated previous findings of increased CD symptoms as a consequence of childhood poverty. This effect proved statistically mediated by OFC volume and exposure to life stress and smoking during pregnancy, but not by childhood maltreatment and maternal responsiveness. These findings underline the importance of studying the impact of early life adversity on brain alterations and highlight the need for programs to decrease income-related disparities.

Does body shaping influence brain shape? Habitual physical activity is linked to brain morphology independent of age.

OBJECTIVES: Physical activity (PA) was found to influence human brain morphology. However, the impact of PA on brain morphology was mainly demonstrated in seniors. We investigated healthy individuals across a broad age range for the relation between habitual PA and brain morphology. METHODS: Ninety-five participants (19-82 years) were assessed for self-reported habitual PA with the "Baecke habitual physical activity questionnaire", and T1-weighted magnetic resonance images were evaluated with whole brain voxel based morphometry for gray and white matter volumes and densities. RESULTS: Regression analyses revealed a positive relation between the extent of physical activity and gray matter volume bilaterally in the anterior hippocampal and parahippocampal gyrus independent of age and gender. Age as well as leisure and locomotion activities were linked to enhanced white matter volumes in the posterior cingulate gyrus and precuneus, suggesting a positive interaction especially in seniors. CONCLUSIONS: Habitual physical activity is associated with regional volumetric gray and white matter alterations. The positive relation of hippocampal volume and physical activity seems not to be restricted to seniors. Thus, habitual physical activity should be generally considered as an influencing factor in studies investigating medial temporal lobe volume and associated cognitive functions (memory), especially in psychiatric research.