Biology subjects

Montag, C.

Publications and source records attributed to Montag, C..

14 recordsLinked to original sources

bioRxiv2024

State and trait serotonin variations interact to shape the intrinsic connectivity and gradient architecture of the brain: a combined TPH2 genetics and tryptophan depletion study

BackgroundSerotonin (5-HT) critically regulates cognitive and emotional functions, and both stable and transient variations in 5-HT signaling have been associated with emotional dysregulations. However, findings regarding the neurofunctional effects of transient 5-HT variations have been highly inconsistent. Therefore, we examined whether individual variations in a central 5-HT-regulating genetic polymorphism (tryptophan hydroxylase 2, TPH2) represent a vulnerability or resilience factor for the effects of acute tryptophan depletion (ATD) on functional brain architecture. MethodThe current study utilized a pharmacogenetic within-subject randomized placebo-controlled resting-state fMRI design with n=53 healthy male participants in combination with spontaneous intrinsic neural activity, functional connectivity, and connectome gradient analyses to compare the neurofunctional effects of ATD-induced transient reduction in central 5-HT signaling between TPH2 genotypes (a priori genotyping for rs4570625, GG n = 25 vs. TT n = 23). ResultsATD induced significant increases in spontaneous neural activity in hippocampal CA1 irrespective of genotype and enhanced communication of this region with the bilateral amygdala and the vmPFC specifically in GG carriers. ATD sharpened the intrinsic connectome gradient architecture in several large-scale networks, including the salience, frontoparietal, and default mode network. ConclusionsOur results identify a potential genetic marker for an increased vulnerability to the neural effects of transient variations in 5-HT signaling on the functional architecture of an anxiety- and stress-related brain circuit. Connectome gradient results underscore the regulatory role of 5-HT on the intricate organization of large-scale networks involved in emotional reactivity and regulation.

neuroscience↗

bioRxiv2024

Disruption of sustained attention and orbitofrontal cortex engagement by incoming social media messages vary as a function of problematic social media use

BackgroundSmartphones and social media have become ubiquitous in our lives, and while debates about their negative impact on mental health, addictive potential, and disruptive effects on daily activities have surged, neurobiological evidence remains scarce. Here, we investigated whether the behavioral and neural effects of interference of continuous attention by incoming social media messages on WeChat varies according to its problematic use as assessed via an addiction framework. MethodsN = 60 healthy individuals were stratified based on their level of problematic WeChat usage as measured by the WeChat Addiction Scale (WAS): LOW (15 males and 15 females) and HIGH (15 males and 15 females) addictive tendencies. Participants underwent an AX-Continuous Performance Task (AX-CPT) with WeChat-associated (incoming message) and neutral auditory distractors as well as a no distractor condition. Concurrent functional Near-Infrared Spectroscopy (fNIRS) assessments of the orbitofrontal cortex (OFC) were implemented to determine the underlying neurofunctional mechanisms. ResultsOn the behavioral level the HIGH group demonstrated faster reaction times during the WeChat and no distractor condition compared to the LOW group. Exploratory analyses indicated that the WeChat distraction decreased left lateral OFC activity in the LOW but enhanced activity in this region in the HIGH group. ConclusionAgainst our hypotheses WeChat distraction enhanced behavioral performance specially in individual with a tendency for problematic WeChat use, with the neural data pointing to less suppression of the OFC in individuals with a tendency for problematic usage. Findings underscore the complexity of the potential effects of new technology on daily live and indicate that addiction models might not be simply extendable to problematic social media usage.

neuroscience↗

bioRxiv2022

Fear of missing out (FOMO) associates with reduced cortical thickness in core regions of the posterior default mode network and higher levels of problematic smartphone and social media use

Fear of missing out (FOMO) promotes the desire or urge to stay continuously connected with a social reference group and updated on their activities, which may result in escalating and potentially addictive smartphone and social media use. The present study aimed to determine whether the neurobiological basis of FOMO encompasses core regions of the reward or social brain, and the associations with the level of problematic smartphone or social media use. We capitalized on a dimensional neuroimaging approach to examine cortical thickness and subcortical volume associations in a comparably large sample of healthy young individuals (n = 167). Meta-analytic network and behavioral decoding were employed to further characterize the identified regions. Higher levels of FOMO associated with lower cortical thickness in the precuneus. In contrast, no associations between FOMO and variations in striatal morphology were observed. Meta-analysis decoding revealed that the identified precuneus region exhibited a strong functional interaction with the default mode network (DMN) engaged in social cognitive and self-referential domains. Together the present findings suggest that individual variations in FOMO are associated with the brain structural architecture of the right precuneus, a core hub within a large-scale functional network resembling the DMN involved in social and self-referential processes. FOMO may promote escalating social media and smartphone use via social and self-referential processes rather than reward-related processes per se.

neuroscience↗

bioRxiv2022

Opposing associations of Internet Use Disorder symptom domains with structural and functional organization of the striatum: a dimensional neuroimaging approach

BackgroundAccumulating evidence suggests brain structural and functional alterations in Internet Use Disorder (IUD). However, conclusions are strongly limited due to the retrospective case-control design of the studies, small samples, and the focus on general rather than symptom-specific approaches. MethodsWe here employed a dimensional multi-methodical MRI-neuroimaging design in a final sample of n = 203 subjects to examine associations between levels of IUD and its symptom-dimensions (loss of control/time management, craving/social problems) with brain structure, resting state and task-based (pain empathy, affective go/no-go) brain function. ResultsAlthough the present sample covered the entire range of IUD, including normal, problematic as well as pathological levels, general IUD symptom load was not associated with brain structural or functional alterations. However, the symptom-dimensions exhibited opposing associations with the intrinsic and structural organization of the brain, such that loss of control/time management exhibited negative associations with intrinsic striatal networks and hippocampal volume, while craving/social problems exhibited a positive association with intrinsic striatal networks and caudate volume. ConclusionsOur findings provided the first evidence for IUD symptom-domain specific associations with progressive alterations in the intrinsic structural and functional organization of the brain, particularly of striatal systems involved in reward, habitual and cognitive control processes.

neuroscience↗

bioRxiv2020

Resting state brain signal complexity of young healthy adults reflects genetic risk for developing Alzheimer Disease

The e4 allele of the APOE gene is strongly associated with impaired brain functionality and cognitive decline in humans at older age. It is controversial whether and how the APOE e4 allele is affecting brain activity among young healthy individuals and how such effects may contribute to individual differences in cognitive performance. Signal complexity is a critical aspect of brain activity that has been shown to be associated with brain function. In this study, we analyzed multiscale entropy (MSE) of EEG signals among young healthy adults as an indicator of brain signal complexity and investigated how MSE is predicted by APOE genotype groups. Furthermore, by means of structural equation modeling, we investigated whether MSE predicts fluid intelligence. Results indicate larger MSE in young healthy e4 carriers across all time scales. Moreover, better fluid intelligence (gf) is associated with smaller MSE at low time scales and larger MSE at higher scales. However, MSE does not account for better cognitive performance among APOE e4 carriers by mediating the APOE genotype effect on fluid intelligence. The present results shed further light on the neural mechanisms underlying gene-behavior association relevant for Alzheimers Disease risk.

neuroscience↗

bioRxiv2020

Multisensory processes can compensate for attention deficits in schizophrenia

Studies on schizophrenia (SCZ) and aberrant multisensory integration (MSI) show conflicting results. These divergent results are potentially confounded by attention deficits in SCZ. To test this, we examined the interplay between MSI and intersensory attention (IA) in healthy controls (N=27) and in SCZ (N=27). Evoked brain potentials to unisensory-visual (V), unisensory-tactile (T) or bisensory VT stimuli were measured with high density electroencephalography, whilst participants attended block-wise to either visual or tactile inputs. Behaviourally, IA effects in SCZ are uncompromised for bisensory stimuli, but diminished for unisensory stimuli. At the neural level, we observed reduced IA effects for bisensory stimuli over mediofrontal scalp regions (230-320ms) in SCZ. The analysis of MSI revealed multiple phases of integration over occipital and frontal scalp regions (240-364ms), with comparable performance between HC and SCZ. The magnitudes of IA and MSI effects were both positively related to the behavioural performance in SCZ, indicating that IA and MSI mutually facilitate bisensory stimulus processing. Our study suggests that widely intact MSI, which facilitates stimulus processing, can compensate for top-down attention deficits in SCZ. Further, the interplay of IA and MSI implies that differences in attentional demands may account for previous conflicting findings on MSI in schizophrenia.

neuroscience↗

bioRxiv2019

Dimensional neuroimaging: (Internet) Gaming Disorder symptoms according to the WHO and APA frameworks associate with lower striatal volume

Growing concerns about the addictive nature of internet and computer games led to the endorsement of Internet Gaming Disorder (IGD) as an emerging disorder by the American Psychological Association (APA) in 2013 and the recognition of Gaming Disorder (GD) as a new diagnosis by the World Health Organization (WHO) in 2019. While the definition of clear diagnostic criteria for IGD is beneficial for clinicians and those in need of treatment, it may also stigmatize normal behavior. Furthermore, the neurobiological mechanisms underlying IGD symptoms, and whether they resemble those of other addictive disorders remains highly debated. To this end the present study employed a dimensional imaging approach to determine associations between IGD symptom-load according to the APA and WHO diagnostic frameworks and brain structure in a comparably large sample of healthy subjects. It was found that higher symptom-load on psychometric tests assessing the APA and WHO diagnostic frameworks convergently associated with lower volumes of the striatum. The present results suggest for the first time a neurobiological foundation of the proposed diagnostic criteria for IGD according to both diagnostic classification systems, further indicating that the transition from non-disordered to disordered gaming is accompanied by progressive neuroplastic changes in the striatum, thus resembling progressive changes in other addictive disorders.

neuroscience↗

bioRxiv2019

Gene - Environment Interaction: A TPH2 polymorphism and early life stress shape brain architecture and anxious avoidant behavior

BackgroundEarly life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2), and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by anxious avoidance. MethodsThe present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). ResultsHigher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. ConclusionsThe present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat avoidance, thus promoting early adaptation to an adverse environment.

neuroscience↗

bioRxiv2019

Oxytocin modulation of self-other distinction is replicable and influenced by oxytocin receptor (OXTR) genotype

Intranasal oxytocin (OXT) has been associated with effects on diverse social-emotional domains in humans, however progress in the field is currently hampered by poor replicability. Limited statistical power and individual differences in biological factors, such as oxytocin receptor (OXTR) genetics, may have contributed to these variable findings. To this end, we present a pharmaco-genetic study aiming at (1) replicating previous findings suggesting that intranasal oxytocin (24 IU) blurs self-other distinction in a large sample of n = 170 male subjects, (2) determining whether variations in common receptor polymorphisms (rs237887, rs2268491, rs2254298, rs53576, rs2268498) influence sensitivity to oxytocins behavioral effects. Employing a validated oxytocin-sensitive trait judgment paradigm, we confirmed that it blurred self-other distinction in terms of decision time and subsequent memory. However, oxytocin only influenced decision time in rs53576 G carriers, whereas effects on memory performance were most pronounced in rs2268498 TT homozygotes. In summary, the current study replicates our previous findings showing that oxytocin blurs self-other distinction and suggests that sensitivity to its effects in this domain are receptor genotype dependent.

neuroscience↗

bioRxiv2018

Altered resting state functional connectivity in a thalamo-cortico-cerebellar network in patients with schizophrenia

Schizophrenia is described as a disease in which complex psychopathology together with cognitive and behavioral impairments are related to widely disrupted brain circuitry causing a failure in coordinating information across multiple brain sites. This led to the hypothesis of schizophrenia as a network disease e.g. in the cognitive dysmetria model and the dysconnectivity theory. Nevertheless, there is no consensus regarding localized mechanisms, namely dysfunction of certain networks underlying the multifaceted symptomatology.\n\nIn this study, we investigated potential functional disruptions in 35 schizophrenic patients and 41controls using complex cerebral network analysis, namely network-based statistic (NBS) and graph theory in resting state fMRI. NBS can reveal locally impaired subnetworks whereas graph analysis characterizes whole brain network topology.\n\nUsing NBS we observed a local hyperconnected thalamo-cortico-cerebellar subnetwork in the schizophrenia group. Furthermore, nodal graph measures retrieved from the thalamo-cortico-cerebellar subnetwork revealed that the total number of connections from/to (degree) of the thalamus is higher in patients with schizophrenia. Interestingly, graph analysis on the whole brain functional networks did not reveal group differences. Together, our results suggest that disruptions in the brain networks of schizophrenia patients are situated at the local level of the hyperconnected thalamo-cortico-cerebellar rather than globally spread in brain.\n\nOur results provide further evidence for the importance of the thalamus and cerebellum in schizophrenia and to the notion that schizophrenia is a network disease in line with the dysconnectivity theory and cognitive dysmetria model.

neuroscience↗

bioRxiv2018

Oxytocin effects on brain and behavior are influenced by dose-frequency and receptor genotype: therapeutic implications

BackgroundThere is considerable interest in therapeutic application of intranasal oxytocin in psychiatric disorders, but while clinical trials typically use daily dosing protocols it has not been established whether this is optimal or if there are moderating influences of oxytocin receptor genotype. MethodsIn a randomized, placebo-controlled pre-registered trial on 138 adult male subjects we investigated effects of single and repeated (24IU daily versus alternate days for 5 days) doses of oxytocin on two neural biomarkers (attenuated amygdala fear reactivity and increased intrinsic amygdala-prefrontal functional connectivity) and modulating effects of oxytocin receptor polymorphisms rs53576 and rs2254298 strongly associated with autism. ResultsFindings confirmed that after a single dose, amygdala responses to fear faces were reduced and its resting state connectivity with medial frontal cortex increased. Suppression of amygdala responses to fear faces was restricted to AA homozygotes of rs53576 and A+ carriers of rs2254298, whereas resting state effects were not genotype-dependent. Importantly, amygdala responses to fear faces were absent after daily oxytocin treatment but maintained after treatment every other day with infrequent dosing additionally resulting in reduced behavioral ratings of emotional arousal and intensity after 5 days. In contrast, oxytocin effects on intrinsic amygdala-prefrontal coupling were similar following daily or infrequent dose protocols after 5 days. ConclusionsOverall, results suggest that infrequent rather than daily doses of oxytocin may be more effective therapeutically and that its actions in reducing amygdala responses to fear are strongly genotype-dependent. The study was pre-registered at Clinical Trials.gov (NCT03610919).

neuroscience↗

bioRxiv2018

Reduced Resting-State Connectivity in the Precuneus is correlated with Apathy in Patients with Schizophrenia

A diagnosis of schizophrenia is associated with a heterogeneous psychopathology including positive and negative symptoms. The disconnection hypothesis, an early pathophysiological framework conceptualizes the diversity of symptoms as a result from disconnections in neural networks. In line with this hypothesis, previous neuroimaging studies of patients with schizophrenia reported alterations within the default mode network (DMN), the most prominent network at rest.\n\nAim of the present study was to investigate the functional connectivity during rest in patients with schizophrenia and healthy individuals and explore whether observed functional alterations are related to the psychopathology of patients. Therefore, functional magnetic resonance images at rest were recorded of 35 patients with schizophrenia and 41 healthy individuals. Independent component analysis (ICA) was used to extract resting state networks.\n\nComparing ICA results between groups indicated alterations only within the network of the DMN. More explicitly, reduced connectivity in the precuneus was observed in patients with schizophrenia compared to healthy controls. Connectivity in this area was negatively correlated with the severity of negative symptoms, more specifically with the domain of apathy.\n\nTaken together, the current results provide further evidence for a role DMN alterations might play in schizophrenia and especially in negative symptom such as apathy.

neuroscience↗

bioRxiv2018

New graph-theoretical-multimodal approach using temporal and structural correlations reveal disruption in the thalamo-cortical network in patients with schizophrenia

Schizophrenia has been understood as a network disease with altered functional and structural connectivity in multiple brain networks compatible to the extremely broad spectrum of psychopathological, cognitive and behavioral symptoms in this disorder.\n\nWhen building brain networks, functional and structural networks are typically modelled independently: functional network models are based on temporal correlations among brain regions, whereas structural network models are based on anatomical characteristics. Combining both features may give rise to more realistic and reliable models of brain networks.\n\nIn this study, we applied a new flexible graph-theoretical-multimodal model called FD (F, the functional connectivity matrix, and D, the structural matrix) to construct brain networks combining functional, structural and topological information of MRI measurements (structural and resting state imaging) to patients with schizophrenia (N=35) and matched healthy individuals (N=41). As a reference condition, the traditional pure functional connectivity (pFC) analysis was carried out.\n\nBy using the FD model, we found disrupted connectivity in the thalamo-cortical network in schizophrenic patients, whereas the pFC model failed to extract group differences after multiple comparison correction. We interpret this observation as evidence that the FD model is superior to conventional connectivity analysis, by stressing relevant features of the whole brain connectivity including functional, structural and topological signatures. The FD model can be used in future research to model subtle alterations of functional and structural connectivity resulting in pronounced clinical syndromes and major psychiatric disorders. Lastly, FD is not limited to the analysis of resting state fMRI, and can be applied to EEG, MEG etc.

neuroscience↗

bioRxiv2018

Oxytocin promotes lying for personal gain in a genotype-dependent manner

Society values honesty, since it fosters trust in others. Although we have a strong moral aversion to lying, particularly when it is self-serving, we nevertheless lie quite frequently and the biological basis for this is poorly understood. The hypothalamic neuropeptide oxytocin has been implicated in a number of anti-social as well as pro-social behaviours, including lying to benefit in-group members or in competitive situations. The aim of the present study was to investigate the effects of oxytocin administration on self-serving lying behaviour and possible moderating effects of genetic underpinnings of the oxytocin receptor. A total of 161 adult men participated in a randomized double-blind placebo-controlled between-subject intranasal oxytocin administration (24 International Units) study where self-serving lying was assessed using the die-in-a-cup paradigm. Additionally, contributions of polymorphisms in the oxytocin receptor gene were investigated using a haplotype approach. Results showed that while placebo-treated subjects behaved honestly across three successive rounds, oxytocin administration promoted self-serving lying, particularly in the third / last round and only to a certain degree (not to the maximum). Moreover, this effect of oxytocin was strongest in carriers of the GCG individual haplotype (rs237887-rs2268491-rs2254298) and non-carriers of the GT individual haplotype (rs53576-rs2268498) on the oxytocin receptor gene. Overall our findings demonstrate that oxytocin administration can promote self-serving lying when subjects are given repeated opportunities to lie and that these effects are moderated by genetic underpinnings of the oxytocin receptor.

genetics↗