Attention-Driven Modulation of Auditory Cortex Activity during Selective Listening in a Multispeaker Setting.

Real-world listening settings often consist of multiple concurrent sound streams. To limit perceptual interference during selective listening, the auditory system segregates and filters the relevant sensory input. Previous work provided evidence that the auditory cortex is critically involved in this process and selectively gates attended input toward subsequent processing stages. We studied at which level of auditory cortex processing this filtering of attended information occurs using functional magnetic resonance imaging (fMRI) and a naturalistic selective listening task. Forty-five human listeners (of either sex) attended to one of two continuous speech streams, presented either concurrently or in isolation. Functional data were analyzed using an inter-subject analysis to assess stimulus-specific components of ongoing auditory cortex activity. Our results suggest that stimulus-related activity in the primary auditory cortex and the adjacent planum temporale are hardly affected by attention, whereas brain responses at higher stages of the auditory cortex processing hierarchy become progressively more selective for the attended input. Consistent with these findings, a complementary analysis of stimulus-driven functional connectivity further demonstrated that information on the to-be-ignored speech stream is shared between the primary auditory cortex and the planum temporale but largely fails to reach higher processing stages. Our findings suggest that the neural processing of ignored speech cannot be effectively suppressed at the level of early cortical processing of acoustic features but is gradually attenuated once the competing speech streams are fully segregated.

Graph-theoretical insights into the effects of aging on the speech production network.

Speech production relies on the interplay of different brain regions. Healthy aging leads to complex changes in speech processing and production. Here, we investigated how the whole-brain functional connectivity of healthy elderly individuals differs from that of young individuals. In total, 23 young (aged 24.6 ± 2.2 years) and 23 elderly (aged 64.1 ± 6.5 years) individuals performed a picture naming task during functional magnetic resonance imaging. We determined whole-brain functional connectivity matrices and used them to compute group averaged speech production networks. By including an emotionally neutral and an emotionally charged condition in the task, we characterized the speech production network during normal and emotionally challenged processing. Our data suggest that the speech production network of elderly healthy individuals is as efficient as that of young participants, but that it is more functionally segregated and more modularized. By determining key network regions, we showed that although complex network changes take place during healthy aging, the most important network regions remain stable. Furthermore, emotional distraction had a larger influence on the young group's network than on the elderly's. We demonstrated that, from the neural network perspective, elderly individuals have a higher capacity for emotion regulation based on their age-related network re-organization.

Distributed networks for auditory memory differentially contribute to recall precision.

Re-directing attention to objects in working memory can enhance their representational fidelity. However, how this attentional enhancement of memory representations is implemented across distinct, sensory and cognitive-control brain network is unspecified. The present fMRI experiment leverages psychophysical modelling and multivariate auditory-pattern decoding as behavioral and neural proxies of mnemonic fidelity. Listeners performed an auditory syllable pitch-discrimination task and received retro-active cues to selectively attend to a to-be-probed syllable in memory. Accompanied by increased neural activation in fronto-parietal and cingulo-opercular networks, valid retro-cues yielded faster and more perceptually sensitive responses in recalling acoustic detail of memorized syllables. Information about the cued auditory object was decodable from hemodynamic response patterns in superior temporal sulcus (STS), fronto-parietal, and sensorimotor regions. However, among these regions retaining auditory memory objects, neural fidelity in the left STS and its enhancement through attention-to-memory best predicted individuals' gain in auditory memory recall precision. Our results demonstrate how functionally discrete brain regions differentially contribute to the attentional enhancement of memory representations.

Fiber tracing and microstructural characterization among audiovisual integration brain regions in neonates compared with young adults.

Audiovisual integration has been related with cognitive-processing and behavioral advantages, as well as with various socio-cognitive disorders. While some studies have identified brain regions instantiating this ability shortly after birth, little is known about the structural pathways connecting them. The goal of the present study was to reconstruct fiber tracts linking AVI regions in the newborn in-vivo brain and assess their adult-likeness by comparing them with analogous fiber tracts of young adults. We performed probabilistic tractography and compared connective probabilities between a sample of term-born neonates (N = 311; the Developing Human Connectome Project (dHCP, http://www.developingconnectome.org) and young adults (N = 311 The Human Connectome Project; https://www.humanconnectome.org/) by means of a classification algorithm. Furthermore, we computed Dice coefficients to assess between-group spatial similarity of the reconstructed fibers and used diffusion metrics to characterize neonates' AVI brain network in terms of microstructural properties, interhemispheric differences and the association with perinatal covariates and biological sex. Overall, our results indicate that the AVI fiber bundles were successfully reconstructed in a vast majority of neonates, similarly to adults. Connective probability distributional similarities and spatial overlaps of AVI fibers between the two groups differed across the reconstructed fibers. There was a rank-order correspondence of the fibers' connective strengths across the groups. Additionally, the study revealed patterns of diffusion metrics in line with early white matter developmental trajectories and a developmental advantage for females. Altogether, these findings deliver evidence of meaningful structural connections among AVI regions in the newborn in-vivo brain.

Quantitative magnetic resonance imaging for segmentation and white matter extraction of the hypothalamus.

Since the hypothalamus is involved in many neuroendocrine, metabolic, and affective disorders, detailed hypothalamic imaging has become of major interest to better characterize disease-induced tissue damages and abnormalities. Still, image contrast of conventional anatomical magnetic resonance imaging lacks morphological detail, thus complicating complete and precise segmentation of the hypothalamus. The hypothalamus' position lateral to the third ventricle and close proximity to white matter tracts including the optic tract, fornix, and mammillothalamic tract display one of the remaining shortcomings of hypothalamic segmentation, as reliable exclusion of white matter is not yet possible. Recent studies found that quantitative magnetic resonance imaging (qMRI), a method to create maps of different standardized tissue contents, improved segmentation of cortical and subcortical brain regions. So far, this has not been tested for the hypothalamus. Therefore, in this study, we investigated the usability of qMRI and diffusion MRI for the purpose of detailed and reproducible manual segmentation of the hypothalamus and data-driven white matter extraction and compared our results to recent state-of-the-art segmentations. Our results show that qMRI presents good contrast for delineation of the hypothalamus and white matter, and that the properties of these images differ between subunits, such that they can be used to reliably exclude white matter from hypothalamic tissue. We propose that qMRI poses a useful addition to detailed hypothalamic segmentation and volumetry.

Amygdala reactivity and ventromedial prefrontal cortex coupling in the processing of emotional face stimuli in attention-deficit/hyperactivity disorder.

Impaired emotion recognition is common in individuals with attention-deficit/hyperactivity disorder (ADHD) and may, via deficient emotion self-regulation, relate to the frequently co-occurring affective and social problems. The present study used an emotional face-matching task and functional magnetic resonance imaging (fMRI) to investigate neural responses during the processing of angry and fearful faces and visuo-spatial control stimuli. Additionally, measures for emotion dysregulation, ADHD type, and age were investigated in relation to the behavioral and neural fMRI data. We utilized a sample of 61 adolescents/young adults with ADHD and 51 age-matched healthy controls (age range: 12-28 years). Participants with ADHD had higher emotion dysregulation scores than controls. They also reacted slower and less accurate in response to emotional but not visuo-spatial control stimuli. Neural response differences between emotional and visuo-spatial trials were significantly smaller in cases, particularly in the left amygdala. While coupling between the right amygdala and bilateral ventromedial prefrontal cortex was stronger for emotional than visuo-spatial stimuli in control subjects, levels of positive coupling between the trial types did not significantly differ in participants with ADHD. Neither emotion dysregulation scores, nor ADHD type or age were related to the behavioral and neural processing alterations during the emotional face-matching task. Results indicate that emotion recognition deficits in ADHD are particularly associated with lower amygdala activation to emotional stimuli and alterations in the functional connections of the amygdala to medial prefrontal areas. Emotion recognition deficits and associated neural alterations were unrelated to emotion dysregulation, ADHD type, or age.

Emotion dysregulation and integration of emotion-related brain networks affect intraindividual change in ADHD severity throughout late adolescence.

The course of attention deficit hyperactivity disorder (ADHD) from adolescence into adulthood shows large variations between individuals; nonetheless determinants of interindividual differences in the course are not well understood. A frequent problem in ADHD, associated with worse outcomes, is emotion dysregulation. We investigated whether emotion dysregulation and integration of emotion-related functional brain networks affect interindividual differences in ADHD severity change. ADHD severity and resting state neuroimaging data were measured in ADHD and unaffected individuals at two points during adolescence and young adulthood. Bivariate latent change score models were applied to investigate whether emotion dysregulation and network integration affect ADHD severity changes. Emotion dysregulation was gauged from questionnaire subscales for conduct problems, emotional problems and emotional lability. Better emotion regulation was associated with a better course of ADHD (104 participants, 44 females, age range: 12-27). Using graph analysis, we determined network integration of emotion-related functional brain networks. Network integration was measured by nodal efficiency, i.e., the average inverse path distance from one node to all other nodes. A pattern of low nodal efficiency of cortical regions associated with emotion processing and high nodal efficiency in subcortical areas and cortical areas involved in implicit emotion regulation predicted a better ADHD course. Larger nodal efficiency of the right orbitofrontal cortex was related to a better course of ADHD (99 participants, 42 females, age range: 10-29). We demonstrated that neural and behavioral covariates associated with emotion regulation affect the course of ADHD severity throughout adolescence and early adulthood beyond baseline effects of ADHD severity.

Oxytocin Receptor Gene DNA Methylation: A Biomarker of Treatment Response in Obsessive-Compulsive Disorder?

INTRODUCTION: Obsessive-compulsive disorder (OCD) is associated with high chronicity and treatment resistance, indicating the need for early therapy response markers enabling fast and personalized treatment adaptations. Although epigenetic mechanisms such as DNA methylation of the oxytocin receptor (OXTR) gene have previously been linked to OCD pathogenesis, epigenetic markers as predictors of treatment success have not yet been investigated in OCD. OBJECTIVE: For the first time, this therapyepigenetic study aimed to investigate the role of OXTR methylation as a treatment response marker in OCD. METHODS: In total, 113 inpatients with OCD (57 females) were compared to 113 age- and sex-matched healthy controls. Patients were investigated over a 10-week course of standardized, OCD-specific cognitive-behavioral psychotherapy. Clinical response was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline, before in vivo exposure, and after therapy. OXTR exon III methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. RESULTS: Relative OXTR hypermethylation was observed in OCD patients compared to healthy controls. In OCD, higher baseline OXTR methylation was found to predict impaired treatment response at both categorical (responders vs. nonresponders) and dimensional (relative Y-BOCS reduction) levels, whereas lower baseline methylation was related to treatment response and greater symptom improvements. Analysis of Y-BOCS subdimensions revealed that the association between OXTR hypermethylation with impaired treatment response applied especially to symptoms related to obsessions, but not compulsions. CONCLUSIONS: OXTR hypermethylation may constitute a predictive marker of impaired treatment response in OCD and thus carries great potential for future personalized treatment efforts in OCD.

Relationship between Memory Load and Listening Demands in Age-Related Hearing Impairment.

Age-related hearing loss has been associated with increased recruitment of frontal brain areas during speech perception to compensate for the decline in auditory input. This additional recruitment may bind resources otherwise needed for understanding speech. However, it is unknown how increased demands on listening interact with increasing cognitive demands when processing speech in age-related hearing loss. The current study used a full-sentence working memory task manipulating demands on working memory and listening and studied untreated mild to moderate hard of hearing (n = 20) and normal-hearing age-matched participants (n = 19) with functional MRI. On the behavioral level, we found a significant interaction of memory load and listening condition; this was, however, similar for both groups. Under low, but not high memory load, listening condition significantly influenced task performance. Similarly, under easy but not difficult listening conditions, memory load had a significant effect on task performance. On the neural level, as measured by the BOLD response, we found increased responses under high compared to low memory load conditions in the left supramarginal gyrus, left middle frontal gyrus, and left supplementary motor cortex regardless of hearing ability. Furthermore, we found increased responses in the bilateral superior temporal gyri under easy compared to difficult listening conditions. We found no group differences nor interactions of group with memory load or listening condition. This suggests that memory load and listening condition interacted on a behavioral level, however, only the increased memory load was reflected in increased BOLD responses in frontal and parietal brain regions. Hence, when evaluating listening abilities in elderly participants, memory load should be considered as it might interfere with the assessed performance. We could not find any further evidence that BOLD responses for the different memory and listening conditions are affected by mild to moderate age-related hearing loss.

Monoamine Oxidase A Hypomethylation in Obsessive-Compulsive Disorder: Reversibility By Successful Psychotherapy?

BACKGROUND: Epigenetic markers such as DNA methylation of the monoamine oxidase A (MAOA) gene have previously been shown to be altered in anxiety- and stress-related disorders and to constitute a potential mechanism of action of psychotherapeutic interventions such as cognitive behavioral therapy in these disorders. The present study for the first time, to our knowledge, investigated MAOA methylation in patients with obsessive-compulsive disorder applying a longitudinal psychotherapy-epigenetic approach. METHODS: The present sample comprised 14 unmedicated female patients with primary obsessive-compulsive disorder and 14 age- and sex-matched healthy controls. MAOA promoter methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from whole blood before and after an 8- to 10-week semi-standardized, obsessive-compulsive disorder-specific cognitive behavioral therapy. Clinical response was assessed by means of the Yale-Brown Obsessive Compulsive Scale. RESULTS: Significantly lower MAOA promoter methylation was discerned in obsessive-compulsive disorder patients relative to healthy controls. Data were available for 12 patients with obsessive-compulsive disorder and 14 controls. Furthermore, following cognitive behavioral therapy, clinical improvement, i.e., decreases in obsessive-compulsive disorder symptoms as indicated by lower scores on the Yale-Brown Obsessive Compulsive Scale was found to be significantly correlated with increases in MAOA methylation levels in patients (data available for n = 7). CONCLUSIONS: The present pilot data suggest MAOA hypomethylation as a potential risk marker of obsessive-compulsive disorder and an increase in MAOA methylation levels as a possible mechanistic correlate of response to cognitive behavioral therapy in obsessive-compulsive disorder.

DNA hypomethylation of the Krüppel-like factor 11 (KLF11) gene promoter: a putative biomarker of depression comorbidity in panic disorder and of non-anxious depression?

Panic disorder (PD) is one of the most common anxiety disorders and often occurs comorbidly with major depressive disorder (MDD). Altered methylation of the monoamine oxidase A (MAOA) gene has been implicated in the etiology of both PD and MDD. The Krüppel-like factor 11 (KLF11; alias TIEG2), an activating transcription factor of the MAOA gene, has been found to be increased in MDD, but has not yet been investigated in PD. In an effort to further delineate the effects of the KLF11-MAOA pathway in anxiety and affective disorders, KLF11 promoter methylation was analyzed via pyrosequencing of sodium bisulfite-treated DNA isolated from human peripheral blood in two independent samples of PD patients with or without comorbid MDD in a case-control design (sample 1: N = 120) as well as MDD patients with and without anxious depression (sample 2: N = 170). Additionally, in sample 1, KLF11 methylation was correlated with Beck Depression Inventory (BDI-II) scores. No overall association of KLF11 promoter methylation with PD was detected. However, PD patients with comorbid MDD showed significant hypomethylation relative to both healthy controls (p = 0.010) and PD patients without comorbid MDD (p = 0.008). Furthermore, KLF11 methylation was negatively correlated with BDI-II scores in PD patients (p = 0.013). MDD patients without anxious features showed nominally decreased KLF11 methylation in comparison to MDD patients with anxious depression (p = 0.052). The present results suggest KLF11 promoter hypomethylation as a potential epigenetic marker of MDD comorbidity in PD or of non-anxious depression, respectively, possibly constituting a differential pathomechanism in anxiety and mood disorders.

An investigation of genetic variability of DNA methyltransferases DNMT3A and 3B does not provide evidence for a major role in the pathogenesis of panic disorder and dimensional anxiety phenotypes.

While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation-DNA methyltransferases (DNMTs)-has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder.

Hearing-impaired listeners show increased audiovisual benefit when listening to speech in noise.

Recent studies provide evidence for changes in audiovisual perception as well as for adaptive cross-modal auditory cortex plasticity in older individuals with high-frequency hearing impairments (presbycusis). We here investigated whether these changes facilitate the use of visual information, leading to an increased audiovisual benefit of hearing-impaired individuals when listening to speech in noise. We used a naturalistic design in which older participants with a varying degree of high-frequency hearing loss attended to running auditory or audiovisual speech in noise and detected rare target words. Passages containing only visual speech served as a control condition. Simultaneously acquired scalp electroencephalography (EEG) data were used to study cortical speech tracking. Target word detection accuracy was significantly increased in the audiovisual as compared to the auditory listening condition. The degree of this audiovisual enhancement was positively related to individual high-frequency hearing loss and subjectively reported listening effort in challenging daily life situations, which served as a subjective marker of hearing problems. On the neural level, the early cortical tracking of the speech envelope was enhanced in the audiovisual condition. Similar to the behavioral findings, individual differences in the magnitude of the enhancement were positively associated with listening effort ratings. Our results therefore suggest that hearing-impaired older individuals make increased use of congruent visual information to compensate for the degraded auditory input.

Intensity-Dependent Effects of Acute Exercise on Executive Function.

Numerous studies suggest beneficial effects of aerobic exercise at moderate intensity on cognition, while the effects of high-intensity exercise are less clear. This study investigated the acute effects of exercise at moderate and high intensities on executive functions in healthy adults, including functional MRI to examine the underlying neural mechanisms. Furthermore, the association between exercise effects and cardiorespiratory fitness was examined. 64 participants performed in two executive function tasks (flanker and Go/No-go tasks), while functional MR images were collected, following two conditions: in the exercise condition, they cycled on an ergometer at either moderate or high intensity (each n = 32); in the control condition, they watched a movie. Differences in behavioral performance and brain activation between the two conditions were compared between groups. Further, correlations between cardiorespiratory fitness and exercise effects on neural and behavioral correlates of executive performance were calculated. Moderate exercise compared to high-intensity exercise was associated with a tendency towards improved behavioral performance (sensitivity index d') in the Go/No-go task and increased brain activation during hit trials in areas related to executive function, attention, and motor processes (insula, superior frontal gyrus, precentral gyrus, and supplementary motor area). Exercise at high intensity was associated with decreased brain activation in those areas and no changes in behavioral performance. Exercise had no effect on brain activation in the flanker task, but an explorative analysis revealed that reaction times improved after high-intensity exercise. Higher cardiorespiratory fitness was correlated with increased brain activation after moderate exercise and decreased brain activation after high-intensity exercise. These data show that exercise at moderate vs. high intensity has different effects on executive task performance and related brain activation changes as measured by fMRI and that cardiorespiratory fitness might be a moderating factor of acute exercise effects. Thus, our results may contribute to further clarify the neurophysiological mechanisms underlying the beneficial effects of exercise on cognition.

The Right Temporoparietal Junction Supports Speech Tracking During Selective Listening: Evidence from Concurrent EEG-fMRI.

Listening selectively to one out of several competing speakers in a "cocktail party" situation is a highly demanding task. It relies on a widespread cortical network, including auditory sensory, but also frontal and parietal brain regions involved in controlling auditory attention. Previous work has shown that, during selective listening, ongoing neural activity in auditory sensory areas is dominated by the attended speech stream, whereas competing input is suppressed. The relationship between these attentional modulations in the sensory tracking of the attended speech stream and frontoparietal activity during selective listening is, however, not understood. We studied this question in young, healthy human participants (both sexes) using concurrent EEG-fMRI and a sustained selective listening task, in which one out of two competing speech streams had to be attended selectively. An EEG-based speech envelope reconstruction method was applied to assess the strength of the cortical tracking of the to-be-attended and the to-be-ignored stream during selective listening. Our results show that individual speech envelope reconstruction accuracies obtained for the to-be-attended speech stream were positively correlated with the amplitude of sustained BOLD responses in the right temporoparietal junction, a core region of the ventral attention network. This brain region further showed task-related functional connectivity to secondary auditory cortex and regions of the frontoparietal attention network, including the intraparietal sulcus and the inferior frontal gyrus. This suggests that the right temporoparietal junction is involved in controlling attention during selective listening, allowing for a better cortical tracking of the attended speech stream.SIGNIFICANCE STATEMENT Listening selectively to one out of several simultaneously talking speakers in a "cocktail party" situation is a highly demanding task. It activates a widespread network of auditory sensory and hierarchically higher frontoparietal brain regions. However, how these different processing levels interact during selective listening is not understood. Here, we investigated this question using fMRI and concurrently acquired scalp EEG. We found that activation levels in the right temporoparietal junction correlate with the sensory representation of a selectively attended speech stream. In addition, this region showed significant functional connectivity to both auditory sensory and other frontoparietal brain areas during selective listening. This suggests that the right temporoparietal junction contributes to controlling selective auditory attention in "cocktail party" situations.

Audio-visual speech processing in age-related hearing loss: Stronger integration and increased frontal lobe recruitment.

Hearing loss is associated with difficulties in understanding speech, especially under adverse listening conditions. In these situations, seeing the speaker improves speech intelligibility in hearing-impaired participants. On the neuronal level, previous research has shown cross-modal plastic reorganization in the auditory cortex following hearing loss leading to altered processing of auditory, visual and audio-visual information. However, how reduced auditory input effects audio-visual speech perception in hearing-impaired subjects is largely unknown. We here investigated the impact of mild to moderate age-related hearing loss on processing audio-visual speech using functional magnetic resonance imaging. Normal-hearing and hearing-impaired participants performed two audio-visual speech integration tasks: a sentence detection task inside the scanner and the McGurk illusion outside the scanner. Both tasks consisted of congruent and incongruent audio-visual conditions, as well as auditory-only and visual-only conditions. We found a significantly stronger McGurk illusion in the hearing-impaired participants, which indicates stronger audio-visual integration. Neurally, hearing loss was associated with an increased recruitment of frontal brain areas when processing incongruent audio-visual, auditory and also visual speech stimuli, which may reflect the increased effort to perform the task. Hearing loss modulated both the audio-visual integration strength measured with the McGurk illusion and brain activation in frontal areas in the sentence task, showing stronger integration and higher brain activation with increasing hearing loss. Incongruent compared to congruent audio-visual speech revealed an opposite brain activation pattern in left ventral postcentral gyrus in both groups, with higher activation in hearing-impaired participants in the incongruent condition. Our results indicate that already mild to moderate hearing loss impacts audio-visual speech processing accompanied by changes in brain activation particularly involving frontal areas. These changes are modulated by the extent of hearing loss.

Dopaminergic modulation of hemodynamic signal variability and the functional connectome during cognitive performance.

Dopamine underlies important aspects of cognition, and has been suggested to boost cognitive performance. However, how dopamine modulates the large-scale cortical dynamics during cognitive performance has remained elusive. Using functional MRI during a working memory task in healthy young human listeners, we investigated the effect of levodopa (l-dopa) on two aspects of cortical dynamics, blood oxygen-level-dependent (BOLD) signal variability and the functional connectome of large-scale cortical networks. We here show that enhanced dopaminergic signaling modulates the two potentially interrelated aspects of large-scale cortical dynamics during cognitive performance, and the degree of these modulations is able to explain inter-individual differences in l-dopa-induced behavioral benefits. Relative to placebo, l-dopa increased BOLD signal variability in task-relevant temporal, inferior frontal, parietal and cingulate regions. On the connectome level, however, l-dopa diminished functional integration across temporal and cingulo-opercular regions. This hypo-integration was expressed as a reduction in network efficiency and modularity in more than two thirds of the participants and to different degrees. Hypo-integration co-occurred with relative hyper-connectivity in paracentral lobule and precuneus, as well as posterior putamen. Both, l-dopa-induced BOLD signal variability modulation and functional connectome modulations proved predictive of an individual's l-dopa-induced benefits in behavioral performance, namely response speed and perceptual sensitivity. Lastly, l-dopa-induced modulations of BOLD signal variability were correlated with l-dopa-induced modulation of nodal connectivity and network efficiency. Our findings underline the role of dopamine in maintaining the dynamic range of, and communication between, cortical systems, and their explanatory power for inter-individual differences in benefits from dopamine during cognitive performance.

Self- and informant-rated apathy in patients with childhood-onset craniopharyngioma.

INTRODUCTION: The current study aimed to assess whether childhood-onset craniopharyngioma patients suffer from symptoms of apathy, as assessed by patients themselves and their close others. We further analyzed whether apathy scores are related to symptoms of depression. METHODS: Childhood-onset craniopharyngioma patients (n = 35, 16 female, median age = 22) and matched healthy controls (n = 35, 19 female, median age = 21) were asked to complete self-ratings of the Apathy Evaluation Scale, whereas informant-ratings were obtained from their close others. Depression was assessed by self-ratings using the German version of the Center for Epidemiological Studies Depression Scale. As primary outcome measures, self- and informant-rated apathy scores were compared between patients and healthy controls. As secondary outcome measures, differences between self- and informant-rated apathy within the single groups and associations between apathy and depression were analyzed. RESULTS: Compared to healthy controls, patients displayed significantly higher apathy levels in informant-ratings (medianpatients = 18, mediancontrols = 12, p = .021), but not in self-ratings (medianpatients = 11, mediancontrols =12, p = .68). In patients, there was a significant discrepancy between self- and informant-rated apathy and self-rated apathy was related to symptoms of depression. CONCLUSIONS: This is the first study to show that childhood-onset craniopharyngioma patients may be at high risk for apathy. Noteworthy, apathy levels in the patient group were judged to be high by their close others but not by the patients themselves, indicating that many patients were not fully aware of their impairments. As apathy is associated with numerous adverse outcomes affecting everyday life and vocational opportunities, future investigations are needed to identify specific risk factors for apathy. Clinical Trial Registration No: NCT00258453.

Does hearing aid use affect audiovisual integration in mild hearing impairment?

There is converging evidence for altered audiovisual integration abilities in hearing-impaired individuals and those with profound hearing loss who are provided with cochlear implants, compared to normal-hearing adults. Still, little is known on the effects of hearing aid use on audiovisual integration in mild hearing loss, although this constitutes one of the most prevalent conditions in the elderly and, yet, often remains untreated in its early stages. This study investigated differences in the strength of audiovisual integration between elderly hearing aid users and those with the same degree of mild hearing loss who were not using hearing aids, the non-users, by measuring their susceptibility to the sound-induced flash illusion. We also explored the corresponding window of integration by varying the stimulus onset asynchronies. To examine general group differences that are not attributable to specific hearing aid settings but rather reflect overall changes associated with habitual hearing aid use, the group of hearing aid users was tested unaided while individually controlling for audibility. We found greater audiovisual integration together with a wider window of integration in hearing aid users compared to their age-matched untreated peers. Signal detection analyses indicate that a change in perceptual sensitivity as well as in bias may underlie the observed effects. Our results and comparisons with other studies in normal-hearing older adults suggest that both mild hearing impairment and hearing aid use seem to affect audiovisual integration, possibly in the sense that hearing aid use may reverse the effects of hearing loss on audiovisual integration. We suggest that these findings may be particularly important for auditory rehabilitation and call for a longitudinal study.

Synthetic Cannabinoid Use in a Psychiatric Patient Population: A Pilot Study.

BACKGROUND: Consumption of natural cannabis (NC) and synthetic cannabinoids (SCs) has been associated with psychotic disorders. We compared the prevalence of use, consumer profiles, and psychosis-inducing potential of NC and SCs in a specific high-risk population. METHODS: This prospective pilot study included 332 patients (18-64 years, mean 36.83, SD 13.33). Patients' sociodemographics and medical histories as well as illicit substance use and psychiatric symptom histories were collected using a drug consumption survey that assessed the use of new psychoactive substances and the Psychotic Symptoms Interview. RESULTS: In total, 7.2% of all patients, 10.6% of psychotic patients, and 4.5% of nonpsychotic patients reported SC consumption. Compared with SCs, NC was consumed much more frequently by its users (mean 222.73, SD 498.27). NC and SC use induced persistent psychosis. Psychotic symptoms were first experienced by patients with a history of NC or SC use during intoxication and persisted after cessation (>1 year) of drug use. Positive and negative symptoms tended to be more severe in SC and NC users, respectively. CONCLUSIONS: NC and SCs may cause different symptom clusters. These relationships should be further evaluated.