Deep Learning in the Identification of Electroencephalogram Sources Associated with Sexual Orientation.

INTRODUCTION: It is unclear if sexual orientation is a biological trait that has neurofunctional footprints. With deep learning, the power to classify biological datasets without an a priori selection of features has increased by magnitudes. The aim of this study was to correctly classify resting-state electroencephalogram (EEG) data from males with different sexual orientation using deep learning and to explore techniques to identify the learned distinguishing features. METHODS: Three cohorts (homosexual men, heterosexual men, and a mixed sex cohort), one pretrained network on sex classification, and one newly trained network for sexual orientation classification were used to classify sex. Further, Grad-CAM methodology and source localization were used to identify the spatiotemporal patterns that were used for differentiation by the networks. RESULTS: Using a pretrained network for classification of males and females, no differences existed between classification of homosexual and heterosexual males. The newly trained network was able, however, to correctly classify the cohorts with a total accuracy of 83%. The retrograde activation using Grad-CAM technology yielded distinctive functional EEG patterns in the Brodmann area 40 and 1 when combined with Fourier analysis and a source localization. DISCUSSION: This study shows that electrophysiological trait markers of male sexual orientation can be identified using deep learning. These patterns are different from the differentiating signatures of males and females in a resting-state EEG.

Referral to aftercare following inpatient withdrawal treatment and readmission: retrospective chart review of patients with substance use disorders.

AIMS OF THE STUDY: Aftercare following inpatient withdrawal treatment improves the prognosis and prevents future readmissions in patients with substance use disorders. According to the stepped care approach, the setting and intensity of aftercare should be adjusted to the patients' specific needs and resources. This study evaluated the real-life referral to different types of aftercare in Switzerland and the rate of inpatient readmission within a 1-year follow-up. METHODS: All substance use disorder patients admitted for inpatient withdrawal treatment in a Swiss psychiatric hospital between January and December 2016 (n = 497) were included in this retrospective study. Clinical and sociodemographic characteristics were extracted from the electronic medical records and their impact on the likelihood of being referred to a particular type of aftercare (general practitioner, psychiatric outpatient care, psychiatric day clinic, inpatient rehabilitation programme) was evaluated. For each type of referral, we determined the readmission rate within one year after discharge. RESULTS: In the sample of substance use disorder patients (mean age 41 years; 69% male), alcohol use disorder was by far the most frequent substance use disorder. Most patients were referred to psychiatric outpatient care (39.8%), followed by a general practitioner (31.0%), inpatient rehabilitation (19.3%) and psychiatric day clinic (9.9%). Patient characteristics that point to an unfavourable course of disease, including higher symptom severity, history of more than two previous admissions, compulsory admission and treatment discontinuation, were associated with a higher likelihood to be referred to lower-level aftercare (general practitioner, psychiatric outpatient care), whereas patients with lower symptom severity, fewer than two previous admissions, voluntary admission and regular discharge were more likely to be referred to high-intensity aftercare (psychiatric day clinic, inpatient rehabilitation). The readmission rate after one year did not differ between the different settings of aftercare (range 40.4-42.9%). CONCLUSIONS: The findings of this study suggest that patients suffering from severe substance use disorders and/or from an unfavourable course of disease who would benefit from a more intensive aftercare setting, such as psychiatric day clinics or inpatient rehabilitation programs, might be under-treated, whereas patients with a rather favourable prognosis might similarly benefit from a less intensive treatment setting, such as psychiatric outpatient care. Regarding the comparable readmission rates, we recommend considering more efficient resource management by promoting stepped care approaches for substance use disorders and establishing standardised placement criteria in Switzerland.

Automaticity of Early Sexual Attention: An Event-Related Potential Study.

A promising line of research on forensic assessment of paraphilic sexual interest focuses on behavioral measures of visual attention using sexual stimuli as distractors. The present study combined event-related potentials (ERPs) with behavioral measures to investigate whether detection of a hidden sexual preference can be improved with ERPs. Normal variants of sexual orientation were used for a proof-of-concept investigation. Accordingly, 40 heterosexual and 40 gay men participated in the study. Within each group, half of the participants were instructed to hide their sexual orientation. The results showed that a match between sexual orientation and stimulus delays responses and influences ERP before motor responses. Late ERP components showed higher potential in differentiating hidden sexual preferences than motor responses, thereby showing how ERPs can be used in combination with reaction time measures to potentially facilitate the detection of hidden sexual preferences.

Orbitofrontal-Striatal Structural Alterations Linked to Negative Symptoms at Different Stages of the Schizophrenia Spectrum.

Negative symptoms such as anhedonia and apathy are among the most debilitating manifestations of schizophrenia (SZ). Imaging studies have linked these symptoms to morphometric abnormalities in 2 brain regions implicated in reward and motivation: the orbitofrontal cortex (OFC) and striatum. Higher negative symptoms are generally associated with reduced OFC thickness, while higher apathy specifically maps to reduced striatal volume. However, it remains unclear whether these tissue losses are a consequence of chronic illness and its treatment or an underlying phenotypic trait. Here, we use multicentre magnetic resonance imaging data to investigate orbitofrontal-striatal abnormalities across the SZ spectrum from healthy populations with high schizotypy to unmedicated and medicated first-episode psychosis (FEP), and patients with chronic SZ. Putamen, caudate, accumbens volume, and OFC thickness were estimated from T1-weighted images acquired in all 3 diagnostic groups and controls from 4 sites (n = 337). Results were first established in 1 discovery dataset and replicated in 3 independent samples. There was a negative correlation between apathy and putamen/accumbens volume only in healthy individuals with schizotypy; however, medicated patients exhibited larger putamen volume, which appears to be a consequence of antipsychotic medications. The negative association between reduced OFC thickness and total negative symptoms also appeared to vary along the SZ spectrum, being significant only in FEP patients. In schizotypy, there was increased OFC thickness relative to controls. Our findings suggest that negative symptoms are associated with a temporal continuum of orbitofrontal-striatal abnormalities that may predate the occurrence of SZ. Thicker OFC in schizotypy may represent either compensatory or pathological mechanisms prior to the disease onset.

Sociodemographic and Clinical Predictors of the Length of Psychiatric Inpatient Stay of Immigrants in Switzerland.

Immigrants with mental disorders have consistently been reported to spend shorter time in the psychiatric hospital compared to native patients. The aim of this study was to identify sociodemographic, clinical and migration-related predictors of a shorter length of psychiatric inpatient stay among immigrants in Switzerland. All patients of a foreign nationality admitted for inpatient treatment in the year 2016 (N = 279) were included in this study. The sample characteristics were drawn from the register of the psychiatric hospital. Within this sample, self-harm and substance use predicted a shorter inpatient treatment episode whereas disturbances of general psychosocial functioning were a predictor of a longer length of stay. As similar results were also reported for non-immigrant patients, the impact of these specific behavioral and social problems on the length of inpatient stay does not appear to be migrant-specific. Moreover, a country of origin outside Europe was a strong predictor of shorter length of stay pointing to inequalities of inpatient psychiatric treatment within the group of immigrants. Therefore, the cultural background and migrant history of immigrants in psychiatry need stronger consideration in order to eliminate disadvantages in mental health care.

Apathy is not associated with reduced ventral striatal volume in patients with schizophrenia.

BACKGROUND: A growing body of neuroimaging research has revealed a relationship between blunted activation of the ventral striatum (VS) and apathy in schizophrenia. In contrast, the association between reduced striatal volume and apathy is less well established, while the relationship between VS function and structure in patients with schizophrenia remains an open question. Here, we aimed to replicate previous structural findings in a larger independent sample and to investigate the relationship between VS hypoactivation and VS volume. METHODS: We included brain structural magnetic resonance imaging (MRI) data from 60 patients with schizophrenia (SZ) that had shown an association of VS hypoactivation with apathy during reward anticipation and 58 healthy controls (HC). To improve replicability, we applied analytical methods employed in two previously published studies: Voxel-based morphometry and the Multiple Automatically Generated Templates (MAGeT) algorithm. VS and dorsal striatum (DS) volume were correlated with apathy correcting for age, gender and total brain volume. Additionally, left VS activity was correlated with left VS volume. RESULTS: We failed to replicate the association between apathy and reduced VS volume and did not find a correlation with DS volume. Functional and structural left VS measures exhibited a trend-level correlation (rs = 0.248, p = 0.067, r2 = 0.06). CONCLUSIONS: Our present data suggests that functional and structural striatal neuroimaging correlates of apathy can occur independently. Replication of previous findings may have been limited by other factors (medication, illness duration, age) potentially related to striatal volume changes in SZ. Finally, associations between reward-related VS function and structure should be further explored.

Psychiatric Acute Day Hospital as an Alternative to Inpatient Treatment.

For the first time in the Swiss health care system, this evaluation study examined whether patients with acute psychiatric illness who were admitted for inpatient treatment could be treated in an acute day hospital instead. The acute day hospital is characterized by the possibility of direct admission of patients without preliminary consultation or waiting time and is open every day of the week. In addition, it was examined whether and to what extent there are cost advantages for day hospital treatment. Patients who were admitted to the hospital with a referral to an inpatient admission were treated randomly either fully inpatient or in the acute day hospital. As a pilot study, 44 patients were admitted to the study. Evidence of efficacy could be provided for both treatment settings based on significant reduction in psychopathological symptoms and improvement in functional level in the course of treatment. There were no significant differences between the two settings in terms of external assessment of symptoms, subjective symptom burden, functional level, quality of life, treatment satisfaction, and number of treatment days. Treatment in the day hospital was about 45% cheaper compared to inpatient treatment. The results show that acutely ill psychiatric patients of different symptom severity can be treated just as well in an acute day hospital instead of being admitted to the hospital. In addition, when direct treatment costs are considered, there are clear cost advantages for day hospital treatment.

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia.

BACKGROUND: Bipolar disorder I (BD-I) is defined by episodes of mania, depression and euthymic states. These episodes are among other symptoms characterized by altered reward processing and negative symptoms (NS), in particular apathy. However, the neural correlates of these deficits are not well understood. METHODS: We first assessed the severity of NS in 25 euthymic BD-I patients compared with 25 healthy controls (HC) and 27 patients with schizophrenia (SZ). Then, we investigated ventral (VS) and dorsal striatal (DS) activation during reward anticipation in a Monetary Incentive Delayed Task and its association with NS. RESULTS: In BD-I patients NS were clearly present and the severity of apathy was comparable to SZ patients. Apathy scores in the BD-I group but not in the SZ group correlated with sub-syndromal depression scores. At the neural level, we found significant VS and DS activation in BD-I patients and no group differences with HC or SZ patients. In contrast to patients with SZ, apathy did not correlate with striatal activation during reward anticipation. Explorative whole-brain analyses revealed reduced extra-striatal activation in BD-I patients compared with HC and an association between reduced activation of the inferior frontal gyrus and apathy. CONCLUSION: This study found that in BD-I patients apathy is present to an extent comparable to SZ, but is more strongly related to sub-syndromal depressive symptoms. The findings support the view of different pathophysiological mechanisms underlying apathy in the two disorders and suggest that extra-striatal dysfunction may contribute to impaired reward processing and apathy in BD-I.

Impact of Chronic Cannabis Use on Auditory Mismatch Negativity Generation in Schizophrenia Patients.

INTRODUCTION: Cannabis use disorders (CUD) are highly prevalent among patients with schizophrenia (SCZ). Deficient mismatch negativity (MMN) generation is a characteristic finding in SCZ patients and cannabis users. This study therefore examined the effects of CUD on MMN generation in SCZ patients. METHODS: Twenty SCZ - CUD patients, 21 SCZ+CUD patients, and 20 healthy controls (HC) were included in this study. MMN to frequency and duration deviants was elicited within an auditory oddball paradigm and recorded by 32 channel EEG. RESULTS: As expected, SCZ - CUD patients showed reduced frontocentral MMN amplitudes to duration deviants compared to HC. Interestingly, SCZ+CUD patients demonstrated greater MMN amplitudes to duration deviants compared to SCZ - CUD patients at central electrodes with no differences compared to HC. DISCUSSION: These results demonstrate that comorbid cannabis use in SCZ patients might be associated with superior cognitive functioning. It can be assumed that the association between cannabis use and better cognitive performance may be due to a subgroup of cognitively less impaired SCZ patients characterized by lower genetic vulnerability for psychosis.

Patient-Level Predictors of Psychiatric Readmission in Substance Use Disorders.

Repeated psychiatric readmissions are a particular challenge in the treatment of substance use disorders and are associated with substantial burden for patients and their associates and for healthcare providers. Factors affecting readmission rates are heterogeneous and need to be identified to better allocate resources. Within the Swiss healthcare system, such data on substance use disorder patients are largely missing. Understanding these factors might bear important implications for future healthcare planning. Thus here, we examine risk factors of inpatient readmission. We retrospectively analyzed all admissions to the hospital's department of addictive disorders in the year 2016. Patients included in the study were followed over a period of 1 year after discharge regarding readmissions to the clinic. Besides the demographic, social, and economic data, we extracted data concerning patient history, admission, and discharge as well as clinical data regarding type and number of substances abused and comorbid diagnoses. In order to describe severity of cases, we furthermore included the scores of the Health of the Nation Outcome Scale (HoNOS) at admission and at discharge as documented in the medical database. Of the 554 patients included in the study, 228 (41.2%) were readmitted within 12 months. Previous admissions, concomitant use of different substances, presence of psychosis or mania, and a higher severity score at discharge increased the likelihood of readmission. The odds for readmission were furthermore higher in patients not being married, living alone, and being unemployed. When all (bivariate) statistically significant factors are included into a logistic regression model, the previous number of admissions and the HoNOS clinical score at discharge significantly contributed to this model. Our findings stress that patients with higher symptom load at discharge are prone to be readmitted within 12 months. The same applies for patients with previous admissions. These findings suggest that the development of specific interventions to prevent premature discharge before satisfactory symptom remission, in particular in those patients with previous admissions in their patient history, might help to prevent readmissions.

Coercion in substance use disorders: clinical course of compulsory admissions in a Swiss psychiatric hospital.

According to the Swiss legal system, involuntary admission is one of the farthest-reaching incursions into personal autonomy. The effect of compulsory admission in treatment of substance use disorders (SUDs) on variables such as length of stay or leaving treatment before recommended discharge remains elusive. In order to elucidate these effects, we retrospectively analysed the clinical course of treatment of 608 patients who were admitted between November 2016 and October 2017 to the Department of Addictive Disorders of the canton of Aargau. Involuntarily admitted patients showed lower health and social functioning, as measured by the Health of the Nation Outcome Scales (HoNOS), compared with those with voluntary status. In involuntary admissions for SUD treatment, length of stay was significantly shorter and the proportion of patients who left treatment against recommendation was twice as high as in voluntarily admitted patients. Furthermore, if treatment was initiated on a compulsory basis, a subsequent switch to voluntary treatment status appeared to be very uncommon. We conclude that, at least in involuntary admission according to the Swiss legal system, these admissions do not lead to sustained inpatient treatment.

Factors Associated with Length of Stay in a Swiss Mental Hospital.

The aim of this study was to identify factors which are associated with the length of stay in a Swiss mental hospital. Demographical and clinical data of all patients who were admitted to the adult inpatient psychiatric service of the Federal State of Aargau in 2016 were examined regarding their association with the length of stay. The study sample included N = 1479 patients. Mean length of stay was 33 days and the median equalled 26 days. Higher age and a primary diagnosis of psychotic or affective disorder were associated with increased length of stay. In contrast, foreign nationality and compulsory admission were associated with reduced length of stay. While some of our findings were in line with recent findings from Italy and the United Kingdom, others could not be replicated.

Ventral Striatal Dysfunction and Symptom Expression in Individuals With Schizotypal Personality Traits and Early Psychosis.

Striatal abnormalities play a crucial role in the pathophysiology of schizophrenia. Growing evidence suggests an association between aberrant striatal activity during reward anticipation and symptom dimensions in schizophrenia. However, it is not clear whether this holds across the psychosis continuum. The aim of the present study was to investigate alterations of ventral striatal activation during reward anticipation and its relationship to symptom expression in persons with schizotypal personality traits (SPT) and first-episode psychosis. Twenty-six individuals with high SPT, 26 patients with non-affective first-episode psychosis (including 13 with brief psychotic disorder (FEP-BPD) and 13 with first-episode schizophrenia [FEP-SZ]) and 25 healthy controls underwent event-related functional magnetic resonance imaging while performing a variant of the Monetary Incentive Delay task. Ventral striatal activation was positively correlated with total symptom severity, in particular with levels of positive symptoms. This association was observed across the psychosis continuum and within each subgroup. Patients with FEP-SZ showed the strongest elevation of striatal activation during reward anticipation, although symptom levels did not differ between groups in the psychosis continuum. While our results provide evidence that variance in striatal activation is mainly explained by dimensional symptom expression, patients with schizophrenia show an additional dysregulation of striatal activation. Trans-diagnostic approaches are promising in order to disentangle dimensional and categorical neural mechanisms in the psychosis continuum.

Combining actigraphy, ecological momentary assessment and neuroimaging to study apathy in patients with schizophrenia.

BACKGROUND: Apathy can be defined as a reduction of goal-directed behavior and is a strong predictor for poor functional outcome in schizophrenia. However, no objective measure of apathy has been identified and assessment is limited to retrospective interview-based ratings. Here we aimed to identify more precise objective readouts of apathy for translational research and clinical practice. METHODS: We employed a combined approach including interview-based ratings of the two negative symptom factors apathy and diminished expression, actigraphy based measures of spontaneous motor activity and the evaluation of daily activities using ecological momentary assessment. Furthermore, a functional magnetic resonance imaging task for reward anticipation was applied to investigate shared and divergent neural correlates of interview-based and behaviorally measured apathy. RESULTS: We found in 18 schizophrenia patients with high interview-based apathy levels that motor activity was negatively correlated with apathy but not with diminished expression. In contrast, measures of daily activities were not associated with apathy. Neural activation during reward anticipation revealed an association between hypoactivation of the ventral striatum and interview-based apathy as well as hypoactivation of the inferior frontal gyrus and motor activity level. CONCLUSIONS: Spontaneous motor activity is an objective readout of apathy, which was specific and not present for diminished expression. On a neural level, interview-based and objective measures of apathy showed divergent neural correlates in the cortical-striatal network, which suggests dissociable neural processes. Finally, motor activity provides a promising readout for quantifying apathy in both translational research and clinical practice.

[Assement of incapacity to work and the Mini-ICF-APP]. / Rentenrelevante Arbeitsunfähigkeit und Mini-ICF-APP.

OBJECTIVE: According to recent recommendations the Mini-ICF Rating for Limitations of Activities and Participation in Psychological Disorders (Mini-ICF-APP) should be used in the assessment of incapacity to work. However evidence from empirical research in the field is missing. METHODS: The application of the Mini-ICF-APP in the psychiatric assessment of 121 cases was analysed. RESULTS: A significant correlation between capacity to work and the duration of sick-leave with the Mini-ICF-APP sum-score was confirmed. The probability that criteria for disability insurance compensations was fulfilled according to the assessor increased with the Mini-ICF-APP-sum-score. CONCLUSION: Our study provides first empirical evidence regarding the application of the Mini-ICF-APP in the psychiatric assessment of incapacity to work.

Jazz drummers recruit language-specific areas for the processing of rhythmic structure.

Rhythm is a central characteristic of music and speech, the most important domains of human communication using acoustic signals. Here, we investigated how rhythmical patterns in music are processed in the human brain, and, in addition, evaluated the impact of musical training on rhythm processing. Using fMRI, we found that deviations from a rule-based regular rhythmic structure activated the left planum temporale together with Broca's area and its right-hemispheric homolog across subjects, that is, a network also crucially involved in the processing of harmonic structure in music and the syntactic analysis of language. Comparing the BOLD responses to rhythmic variations between professional jazz drummers and musical laypersons, we found that only highly trained rhythmic experts show additional activity in left-hemispheric supramarginal gyrus, a higher-order region involved in processing of linguistic syntax. This suggests an additional functional recruitment of brain areas usually dedicated to complex linguistic syntax processing for the analysis of rhythmical patterns only in professional jazz drummers, who are especially trained to use rhythmical cues for communication.

Response inhibition in pedophilia: an FMRI pilot study.

BACKGROUND: The failure to inhibit pleasurable but inappropriate urges is associated with frontal lobe pathology and has been suggested as a possible cause of pedophilic behavior. However, imaging and neuropsychological findings about frontal pathology in pedophilia are heterogeneous. In our study we therefore address inhibition behaviorally and by means of functional imaging, aiming to assess how inhibition in pedophilia is related to a differential recruitment of frontal brain areas. METHOD: Eleven pedophilic subjects and 7 nonpedophilic controls underwent fMRI while performing a go/no-go task composed of neutral letters. RESULTS: Pedophilic subjects showed a slower reaction time and less accurate visual target discrimination. fMRI voxel-level ANOVA revealed as a main effect of the go/no-go task an activation of prefrontal and parietal brain regions in the no-go condition, while the left anterior cingulate, precuneus and gyrus angularis became more activated in the go condition. In addition, a group × task interaction was found in the left precuneus and gyrus angularis. This interaction was based on an attenuated deactivation of these brain regions in the pedophilic group during performance of the no-go condition. The positive correlation between blood oxygen level-dependent imaging signal and reaction time in these brain areas indicates that attenuated deactivation is related to the behavioral findings. CONCLUSION: Slower reaction time and less accurate visual target discrimination in pedophilia was accompanied by attenuated deactivation of brain areas belonging to the default mode network. Our findings thus support the notion that behavioral differences might also derive from self-related processes and not necessarily from frontal lobe pathology.

Immediate processing of erotic stimuli in paedophilia and controls: a case control study.

BACKGROUND: Most neuroimaging studies investigating sexual arousal in paedophilia used erotic pictures together with a blocked fMRI design and long stimulus presentation time. While this approach allows the detection of sexual arousal, it does not enable the assessment of the immediate processing of erotically salient stimuli. Our study aimed to identify neuronal networks related to the immediate processing of erotic stimuli in heterosexual male paedophiles and healthy age-matched controls. METHODS: We presented erotic pictures of prepubescent children and adults in an event related fMRI-design to eight paedophilic subjects and age-matched controls. RESULTS: Erotic pictures of females elicited more activation in the right temporal lobe, the right parietal lobe and both occipital lobes and erotic pictures of children activated the right dorsomedial prefrontal cortex in both groups. An interaction of sex, age and group was present in the right anteriolateral oribitofrontal cortex. CONCLUSIONS: Our event related study design confirmed that erotic pictures activate some of the brain regions already known to be involved in the processing of erotic pictures when these are presented in blocks. In addition, it revealed that erotic pictures of prepubescent children activate brain regions critical for choosing response strategies in both groups, and that erotically salient stimuli selectively activate a brain region in paedophilic subjects that had previously been attributed to reward and punishment, and that had been shown to be implicated in the suppression of erotic response and deception.

LH-RH agonists modulate amygdala response to visual sexual stimulation: a single case fMRI study in pedophilia.

Pedophilia is characterized by a persistent sexual attraction to prepubescent children. Treatment with anti-androgen agents, such as luteinizing hormone-releasing hormone (LH-RH) agonists, reduces testosterone levels and thereby sexual drive and arousal. We used functional magnetic resonance imaging (fMRI) to compare visual erotic stimulation pre- and on-treatment with the LH-RH agonist leuprolide acetate in the case of homosexual pedophilia. The pre-treatment contrasts of the erotic pictures against the respective neutral pictures showed an activation of the right amygdala and adjacent parahippocampal gyrus that decreased significantly under treatment with leuprolide acetate. Our single case fMRI study supports the notion that anti-androgens may modify amygdala response to visual erotic stimulation, a hypothesis that should be further examined in larger studies.

Musical training induces functional plasticity in human hippocampus.

Training can change the functional and structural organization of the brain, and animal models demonstrate that the hippocampus formation is particularly susceptible to training-related neuroplasticity. In humans, however, direct evidence for functional plasticity of the adult hippocampus induced by training is still missing. Here, we used musicians' brains as a model to test for plastic capabilities of the adult human hippocampus. By using functional magnetic resonance imaging optimized for the investigation of auditory processing, we examined brain responses induced by temporal novelty in otherwise isochronous sound patterns in musicians and musical laypersons, since the hippocampus has been suggested previously to be crucially involved in various forms of novelty detection. In the first cross-sectional experiment, we identified enhanced neural responses to temporal novelty in the anterior left hippocampus of professional musicians, pointing to expertise-related differences in hippocampal processing. In the second experiment, we evaluated neural responses to acoustic temporal novelty in a longitudinal approach to disentangle training-related changes from predispositional factors. For this purpose, we examined an independent sample of music academy students before and after two semesters of intensive aural skills training. After this training period, hippocampal responses to temporal novelty in sounds were enhanced in musical students, and statistical interaction analysis of brain activity changes over time suggests training rather than predisposition effects. Thus, our results provide direct evidence for functional changes of the adult hippocampus in humans related to musical training.