Biology subjects

Becker, B.

Publications and source records attributed to Becker, B..

At least 55 records · Page 3Linked to original sources

bioRxiv2022

Self-navigating the "Island of Reil": a systematic review of real-time fMRI neurofeedback training of insula activity

Real-time fMRI (rtfMRI) neurofeedback (NF) is a novel noninvasive technique that permits individuals to voluntarily control brain activity or connectivity, with demonstrated feasibility in experimental and therapeutic applications. The crucial role of the insula in emotional and salience processing makes it a popular target in rtfMRI studies although there is no systematic review of their efficacy. To promote our understanding of mechanisms underlying insula regulation and thereby facilitate therapeutic translation, the present review identified 22 preclinical and clinical studies and found that rtfMRI-based NF training is efficient for modulating insula activity (> 86%) and its associated behavioral and neural changes. Based on findings, continuous feedback for multiple training sessions, specific strategies validated before application, inclusion of a practice session, and choosing appropriate localization strategies are suggested as guidelines. We also recommend standardization of training protocol design, statistical analyses and results reports for future studies. In summary, the present review informs both fundamental research and therapeutic translation of NF training as an intervention in mental disorders, particularly those with insula dysfunction.

neuroscience↗

bioRxiv2021

Lonely in the dark: trauma memory and sex-specific dysregulation of amygdala reactivity to fear signals

Loneliness exacerbates psychological distress and increases the risk of psychopathology after trauma exposure. The prevalence of trauma-associated disorders varies substantially between sexes, and accumulating evidence indicates sex-specific effects of loneliness. However, it is still unclear whether a lack of social connectedness affects trauma-induced intrusions and the neural processing of fear signals. Moreover, it is uncertain, whether loneliness plays a different role in women and men. We used a prestratification strategy and recruited n=47 (n=20 women) healthy individuals with high loneliness and n=35 controls (n=18 women). Participants were exposed to an experimental trauma and evoked intrusive thoughts in daily life were monitored for three consecutive days. Functional magnetic resonance imaging was used to assess neural habituation to fearful faces and fear learning (conditioning and extinction) prior to trauma exposure. The total number of intrusions and amygdala reactivity in neural fear processing served as the primary study outcomes. Our results revealed a significant interaction between loneliness and sex such that loneliness was associated with more intrusions in men, but not in women. A similar pattern emerged at the neural level, with both reduced amygdala habituation to repeated fearful faces and amygdala hyperreactivity during the conditioning of fear signals in lonely men, but not in women. Our findings indicate that loneliness may confer vulnerability to intrusive memories after trauma exposure in healthy men and that this phenotype relates to altered limbic processing of fear signals. Collectively, interventions targeting social connectedness may mitigate the sequelae of traumatic experiences.

neuroscience↗

bioRxiv2021

Oxytocinergic modulation of stress-associated amygdala-hippocampus pathways in humans is specially mediated by serotonergic mechanisms

BackgroundThe hypothalamic neuropeptide oxytocin (OXT) may exert anxiolytic and stress-reducing actions via modulatory effects on amygdala circuits. Animal models and initial findings in humans suggest that some of these effects are mediated by interactions with other neurotransmitter systems, in particular the serotonin (5-HT) system. Against this background, the present pharmacological resting state fMRI study aimed at determining whether effects of OXT on stress-associated amygdala intrinsic networks are mediated by 5-HT. MethodsWe employed a randomized placebo-controlled double-blind parallel-group pharmacological fMRI resting state experiment during which n = 112 healthy male participants underwent a transient decrease in 5-HT signaling via acute tryptophan depletion (ATD) or the corresponding placebo-control protocols (ATDc) before the administration of intranasal OXT or placebo intranasal spray, respectively. ResultsOXT and 5-HT modulation exerted interactive effects on the coupling of the left amygdala with the ipsilateral hippocampus and adjacent midbrain. OXT increased intrinsic coupling in this pathway, while this effect of OXT was significantly attenuated during transiently decreased central serotonergic signaling induced via ATD. In the absence of OXT or 5-HT modulation this pathway showed a trend for an association with self-reported stress perception in everyday life. No interactive effects were observed for the right amygdala. ConclusionsTogether, the findings provide first evidence that effects of OXT on stress-associated amygdala-hippocampal-midbrain pathways are critically mediated by the 5-HT system in men.

neuroscience↗

bioRxiv2021

Common and distinct neurofunctional representations of core and social disgust in the brain: An ALE meta-analysis and MACM characterization

Disgust represents a multifaceted defensive-avoidance response. On the behavioral level, the response includes withdrawal and a disgust-specific facial expression. While both serve the avoidance of pathogens, the latter additionally transmits social-communicative information. Given that common and distinct brain representation of the primary defensive-avoidance response (core disgust) and encoding of the social-communicative signal (social disgust) remain debated, we employed neuroimaging meta-analyses to (1) determine brain systems generally engaged in disgust processing, and (2) segregate common and distinct brain systems for core and social disgust. Disgust processing, in general, engaged a bilateral network encompassing the insula, amygdala, occipital and prefrontal regions. Core disgust evoked stronger reactivity in left-lateralized threat detection and defensive response network including amygdala, occipital and frontal regions while social disgust engaged a right-lateralized superior temporal-frontal network engaged in social cognition. Anterior insula, inferior frontal and fusiform regions were commonly engaged during core and social disgust, suggesting a common neural basis. We demonstrate a common and separable neural basis of primary disgust responses and encoding of associated social-communicative signals.

neuroscience↗

bioRxiv2021

Modulation of the renin-angiotensin system inhibits memory advantage for negative emotional material via decreasing hippocampus activation and its coupling with the amygdala

Exaggerated arousal and dysregulated emotion-memory interactions are key pathological dysregulations that accompany the development of post-traumatic stress disorder (PTSD). Current treatments for PTSD are of moderate efficacy and preventing the dysregulations already during exposure to threatening events may attenuate the development of PTSD-symptomatology. In a preregistered double-blind, between-subject, placebo-controlled pharmaco-fMRI design, the present proof-of-concept study examined the potential of a single dose of angiotensin II type 1 receptor (AT1R) antagonist losartan (LT) to attenuate the mnemonic advantage of threatening stimuli and the underlying neural mechanism via combining an emotional subsequent memory paradigm with LT (n=29) or placebo treatment (n=30) and a surprise memory test after 24h washout. LT generally improved memory performance and abolished emotional memory enhancement for negative yet not positive material while emotional experience during encoding remained intact. LT further suppressed hippocampus activity during encoding of subsequently remembered negative stimuli. On the network level LT reduced coupling between hippocampus and basolateral amygdala during successful memory formation of negative stimuli. Our findings suggest that LT may have the potential to attenuate memory formation for negative yet not positive information by decreasing hippocampus activity and its functional coupling strength with amygdala. These findings suggest a promising potential of LT to prevent preferential encoding and remembering of negative events, a mechanism that could prevent the emotion-memory dysregulations underlying the development of PTSD-symptomatology.

neuroscience↗

bioRxiv2021

Losartan shifts social reward motivation and punishment feedback sensitivity via modulating midbrain-striato-frontal circuits

Social deficits and dysregulations in dopaminergic midbrain-striato-frontal circuits represent transdiagnostic symptoms across psychiatric disorders. Animal models suggest that interactions between the dopamine and renin-angiotensin system may modulate learning and reward-related processes. The present study therefore examined the behavioral and neural effects of the angiotensin II type 1 receptor (AT1R) antagonist Losartan on social reward and punishment processing in humans. A pre-registered randomized double-blind placebo-controlled between-subject pharmacological design was combined with a social incentive delay fMRI paradigm during which subjects could avoid social punishment or gain social reward. Healthy volunteers received a single-dose of Losartan (50mg, n=43) or placebo (n=44). Reaction times and emotional ratings served as behavioral outcomes, on the neural level activation and connectivity were modelled. Relative to placebo, Losartan modulated the reaction time and arousal differences between social punishment and social reward. On the neural level the Losartan-enhanced motivational salience of social rewards was accompanied by stronger ventral striatum-prefrontal connectivity during reward anticipation. Losartan increased the reward-neutral difference in the ventral tegmental area (VTA) and attenuated VTA associated connectivity with the bilateral insula in response to punishment during the outcome phase. Losartan modulated approach-avoidance motivation and emotional salience during social punishment versus social reward via modulating distinct core nodes of the midbrain-striato-frontal circuits. The findings document a modulatory role of the renin-angiotensin system in these circuits and associated social processes, suggesting a promising treatment target to alleviate social dysregulations. Significance StatementSocial deficits and anhedonia characterize several mental disoders and have been linked to the midbrain-striato-frontal circuits of the brain. Based on initial findings from animal models we here combine the pharmacological blockade of the angiotensin II type 1 receptor (AT1R) via Losartan with functional MRI to demonstrate that AT1R blockade enhances the motivational salience of social rewards and attenuates the negative impact of social punishment via modulating the communication in the midbrain-striato-frontal circuits in humans. The findings demonstrate for the first time an important role of the AT1R in social reward processing in humans and render the AT1R as promising novel treatment target for social and motivational deficits in mental disoders.

neuroscience↗

bioRxiv2021

Structural-functional connectivity mapping of the insular cortex system: A combined data-driven and meta-analytic topic mapping approach

In this study, we examined structural and functional profiles of the insular cortex and mapped associations with well-described functional networks (FNs) throughout the brain using diffusion tensor imaging (DTI) and resting-state functional connectivity (RSFC) data. We used a data-driven method to independently estimate the structural-functional connectivity of the insular cortex. Data were obtained from the Human Connectome Project comprising 108 adult participants. Overall, we observed moderate to high associations between the structural and functional mapping scores of three different insular subregions: the posterior insula (associated with the sensorimotor network: RSFC, DTI = 50% and 72%, respectively), dorsal anterior insula (associated with ventral attention: RSFC, DTI = 83% and 83%, respectively), and ventral anterior insula (associated with the frontoparietal: RSFC, DTI = 42% and 89%, respectively). Further analyses utilized meta-analytic decoding maps to demonstrate specific cognitive and affective as well as gene expression profiles of the three subregions reflecting the core properties of the insular cortex. In summary, given the central role of the insular in the human brain, our results revealing correspondence between DTI and RSFC mappings provide a complementary approach and insight for clinical researchers to identify dysfunctional brain organization in various neurological disorders associated with insular pathology.

neuroscience↗

bioRxiv2021

Intranasal vasopressin like oxytocin increases social attention by influencing top-down control, but additionally enhances bottom-up control

The respective roles of the neuropeptides arginine vasopressin (AVP) and oxytocin (OXT) in modulating social cognition and for therapeutic intervention in autism spectrum disorder have not been fully established. In particular, while numerous studies have demonstrated effects of oxytocin in promoting social attention the role of AVP has not been examined. The present study employed a randomized, double-blind, placebo (PLC)-controlled between-subject design to explore the social- and emotion-specific effects of AVP on both bottom-up and topdown attention processing with a validated emotional anti-saccade eye-tracking paradigm in 80 male subjects (PLC = 40, AVP = 40). Our findings showed that AVP increased the error rate for social (angry, fearful, happy, neutral and sad faces) but not non-social (oval shapes) stimuli during the anti-saccade condition and reduced error rates in the pro-saccade condition. Comparison of these findings with a previous study (sample size: PLC = 33, OXT = 33) using intranasal oxytocin revealed similar effects of the two peptides on anti-saccade errors but a significantly greater effect of AVP on pro-saccades. Both peptides also produced a post-task anxiolytic effect by reducing state anxiety. Together these findings suggested that both AVP and OXT decrease goal-directed top-down attention control to social salient stimuli but that AVP more potently increased bottom-up social attentional processing.

neuroscience↗

bioRxiv2021

The mirror neuron system compensates for amygdala dysfunction-associated social deficits in individuals with higher autistic traits

The amygdala is a core node in the social brain which exhibits structural and functional abnormalities in Autism spectrum disorder and there is evidence that the mirror neuron system (MNS) can functionally compensate for impaired emotion processing following amygdala lesions. In the current study, we employed an fMRI paradigm in 241 subjects investigating MNS and amygdala responses to observation, imagination and imitation of dynamic facial expressions and whether these differed in individuals with higher as opposed to lower autistic traits. Results indicated that individuals with higher compared to lower autistic traits showed reduced left amygdala responses to imitation and enhanced responses in the left superior temporal sulcus (STS) of the MNS to observation, imagination and imitation. Additionally, functional connectivity between the left amygdala and the left STS as well as some other MNS regions was increased in individuals with higher autistic traits, especially during imitation of fearful expressions. The amygdala-MNS connectivity significantly moderated autistic group differences on recognition memory for fearful faces and real-life social network indices, indicating that increased amygdala-MNS connectivity could diminish the social behavioral differences between higher and lower autistic trait groups. Overall, findings demonstrate decreased imitation-related amygdala activity in individuals with higher autistic traits in the context of increased cortical MNS activity and amygdala-MNS connectivity which may functionally compensate for amygdala dysfunction and social deficits. Training targeting the MNS may capitalize on this compensatory mechanism for therapeutic benefits in Autism spectrum disorder.

neuroscience↗

bioRxiv2021

Anxiolytic effects of chronic intranasal oxytocin on neural responses to threat are dose-frequency dependent

Anxiety disorders are prevalent psychiatric conditions characterized by exaggerated anxious arousal and threat reactivity. Animal and human studies suggest an anxiolytic potential of the neuropeptide oxytocin (OT), yet, while a clinical application will require chronic administration protocols previous studies in humans have exclusively focused on single-dose (acute) intranasal OT effects. We aimed at determining whether the anxiolytic effects of OT are maintained with repeated (chronic) administration or are influenced by dose frequency and trait anxiety. A double-blind randomized, placebo-controlled pharmaco-fMRI trial (n=147) determined acute (single-dose) as well as chronic effects of two different dose frequencies of OT (OT administered daily for 5 days or every other day) on emotional reactivity in healthy subjects with high versus low trait anxiety. OT produced valence, dose frequency and trait anxiety specific effects, such that the low-frequency (intermittand) chronic dosage specifically attenuated neural reactivity in amygdala-insula-prefrontal regions in high anxious subjects in response to threatening but not positive stimuli. The present trial provides evidence that low dose frequency chronic oxytocin nasal spray has the potential to alleviate exaggerated neural threat reactivity in subjects with elevated anxiety levels underscoring a treatment potential for anxiety disorders.

neuroscience↗

bioRxiv2021

A realistic touch-transfer method reveals low risk of transmission for SARS-CoV-2 by contaminated coins and bank notes

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created a significant threat to global health. While respiratory aerosols or droplets are considered as the main route of human-to-human transmission, secretions expelled by infected individuals can also contaminate surfaces and objects, potentially creating the risk of fomite-based transmission. Consequently, frequently touched objects such as paper currency and coins have been suspected as a potential transmission vehicle. To assess the risk of SARS-CoV-2 transmission by banknotes and coins, we examined the stability of SARS-CoV-2 and bovine coronavirus (BCoV), as surrogate with lower biosafety restrictions, on these different means of payment and developed a touch transfer method to examine transfer efficiency from contaminated surfaces to skin. Although we observed prolonged virus stability, our results, including a novel touch transfer method, indicate that the transmission of SARS-CoV-2 via contaminated coins and banknotes is unlikely and requires high viral loads and a timely order of specific events.

microbiology↗

bioRxiv2021

Location, location, location- choice of Voxel-Based Morphometry processing pipeline drives variability in the location of neuroanatomical brain markers

Fundamental and clinical neuroscience has benefited from the development of automated computational analyses of Magnetic Resonance Imaging (MRI) data, such as Voxel-based Morphometry (VBM). VBM determines regional gray matter variations with high spatial resolution and results are commonly interpreted in a regional-specific manner, for instance with respect to which specific brain regions differ in volume between women and men. In excess of 600 papers using VBM are now published every year and a number of different automated VBM processing pipelines are frequently used in analyses although it remains to be fully and systematically assessed whether they come up with the same answers. Here we have therefore examined variability between four commonly used VBM pipelines in two large brain structural datasets. Spatial similarity, reproducibility and reliability of the processed gray matter brain maps was generally low between pipelines. Examination of sex-differences and age-related changes in gray matter volumes revealed considerable differences between the pipelines in terms of the specific regions identified as well as meta-analytic characterization of their function. In contrast, applying machine learning-based multivariate analyses allowed an accurate prediction of sex or age based on the gray matter maps across pipelines, although prediction accuracy differed strongly between them. Together the findings suggest that the choice of pipeline alone leads to considerable variability in brain structural analyses which poses a serious challenge for reproducibility as well as interpretation.

neuroscience↗

bioRxiv2020

Secondary rewards acquire enhanced incentive motivation via increasing anticipatory activity of the lateral orbitofrontal cortex

The motivation to strive for and consume primary rewards such as palatable food is bound by internal satiation and devaluation mechanisms, yet secondary rewards such as money may not be bound by these regulatory mechanisms. The present study therefore aimed at determining diverging devaluation trajectories for primary (chocolate milk) and secondary (money) reinforcers on the behavioral and neural level. Satiation procedures combined with a choice (Experiment 1) and an incentive delay (Experiment 2) paradigm consistently revealed decreased hedonic value for the primary reward as reflected by decreasing hedonic evaluation and choice preference, while hedonic value and preferences for the secondary reward increased. Concomitantly acquired functional near-infrared spectroscopy (fNIRS) data during the incentive delay paradigm revealed that increasing value of the secondary reward was accompanied by increasing anticipatory activation in the lateral orbitofrontal cortex, while during the consummatory phase the secondary reinforcer associated with higher medial orbitofrontal activity irrespective of devaluation stage. Overall, the findings suggest that - in contrast to primary reinforcers - secondary reinforcers can acquire progressively enhanced incentive motivation with repeated receipt, suggesting a mechanism which could promote escalating striving to obtain secondary rewards.

neuroscience↗

bioRxiv2020

Segregating domain-general from emotional context-specific inhibitory control systems - ventral striatum and orbitofrontal cortex serve as emotion-cognition integration hubs

Inhibitory control hierarchically regulates cognitive and emotional systems in the service of adaptive goal-directed behavior across changing task demands and environments. While previous studies convergently determined the contribution of prefrontal-striatal systems to general inhibitory control, findings on the specific circuits that mediate the context-specific impact of inhibitory control remained inconclusive. Against this background we employed an evaluated emotional Go/No Go task with fMRI in a large cohort of subjects (N = 250) to segregate brain systems and circuits that mediate domain-general from emotion-specific inhibition control. Particularly during a positive emotional context, behavioral results showed a lower accuracy for No Go trials and a faster response time for Go trials. While the dorsal striatum and lateral frontal regions were involved in inhibitory control irrespective of emotional context, activity in the ventral striatum (VS) and medial orbitofrontal cortex (mOFC) varied as a function of emotional context. On the voxel-wise network level, limbic and striatal systems generally exhibited highest changes in global brain connectivity during inhibitory control, while global brain connectivity of the left mOFC was less suppressed during emotional contexts. Functional connectivity analyses moreover revealed that negative coupling between the VS with inferior frontal gyrus (IFG)/insula and mOFC varied as a function of emotional context. Together these findings indicated separable domain general systems as well emotional context-specific inhibitory brain systems which specifically encompass the VS and its connections with frontal regions.

neuroscience↗

bioRxiv2020

Beyond fear centers: a distributed fMRI-based neuromarker for the subjective experience of fear

The specific neural systems underlying the subjective feeling of fear remain vigorously debated in affective neuroscience. Here, we combined functional MRI with machine learning to identify and evaluate a sensitive and generalizable neural signature predictive of the momentary self-reported subjective fear experience across discovery (n=67), validation (n=20) and generalization (n=31) cohorts. We systematically demonstrate that accurate fear prediction crucially requires distributed brain systems, with important contributions from cortical (e.g., prefrontal, midcingulate and insular cortices) and subcortical (e.g., thalamus, periaqueductal gray, basal forebrain and amygdala) regions. We further demonstrate that the neural representation of subjective fear is distinguishable from the representation of conditioned threat and general negative affect. Overall, our findings suggest that subjective fear, which exhibits distinct neural representation with some other aversive states, is encoded in distributed systems rather than isolated fear centers. This signature provides a neuromarker for monitoring fear-related neuropathology and evaluating novel treatments targeting pathological fear.

neuroscience↗

bioRxiv2020

Decreased homotopic interhemispheric functional connectivity in children with autism spectrum disorder

While a number of functional and structural changes occur in large-scale brain networks in autism spectrum disorder (ASD), reduced interhemispheric resting state functional connectivity (rsFC) between homotopic regions may be of particular importance as a biomarker. ASD is an early-onset developmental disorder and neural alterations are often age-dependent, reflecting dysregulated developmental trajectories, although no studies have investigated whether homotopic interhemispheric rsFC alterations occur in ASD children. The present study conducted a voxel-based homotopic interhemispheric rsFC analysis in 146 SD and 175 typically developing children under age 10 and examined associations with symptom severity in the Autism Brain Imaging Data Exchange datasets. Given the role of corpus callosum (CC) in interhemispheric connectivity and reported CC volume changes in ASD we additionally examined whether there were parallel volumetric changes in ASD children. Results demonstrated decreased homotopic rsFC in ASD children in the medial prefrontal cortex, precuneus and posterior cingulate cortex of the default mode network (DMN), the dorsal anterior cingulate cortex of the salience network, the precentral gyrus and inferior parietal lobule of the mirror neuron system, the lingual, fusiform and inferior occipital gyri of the visual processing network and thalamus. Symptom severity was associated with homotopic rsFC in regions in the DMN and visual processing network. There were no significant CC volume changes in ASD children. The present study shows that reduced homotopic interhemispheric rsFC in brain networks in ASD adults/adolescents is already present in children of 5-10 years old and further supports their potential use as a general ASD biomarker.

neuroscience↗

bioRxiv2020

Virucidal efficacy of different formulations for hand and surface disinfection targeting SARS CoV-2

In the ongoing SARS CoV-2 pandemic effective measures are needed, and guidance based on the methodological framework of the European committee for standardization (CEN) can help to choose effective disinfectants on an immediate basis. This study demonstrates that two commercially available formulations for surface disinfection and one formulation for hand disinfection claiming "virucidal activity against enveloped viruses" are effectively inactivating SARS-CoV-2. This study emphasizes that chemical disinfectants claiming "virucidal activity against enveloped viruses" are an effective choice to target enveloped SARS-CoV-2 as a preventive measure.

microbiology↗

bioRxiv2020

A prospective longitudinal study shows putamen volume is associated with moderate amphetamine use and resultant cognitive impairments

BackgroundAmphetamine-type stimulants (ATS) have become a critical public health issue. Animal models have indicated a clear neurotoxic potential of ATSs. In humans, chronic use has been associated with cognitive deficits and structural brain abnormalities. However, cross-sectional retrospective designs in chronic users cannot truly determine the causal direction of the effects. MethodsIn a prospective-longitudinal study design cognitive functioning and brain structure were assessed at baseline and at 12-months follow-up in occasional ATS users (cumulative lifetime use <10 units at baseline). ResultsExamination of change-scores between the initial examination and follow-up revealed declined verbal memory performance and putamen volume in users with high relative to low interim ATS exposure. In the entire sample interim ATS use, memory decline and putamen volume reductions were strongly associated. ConclusionsThe present findings support the hypothesis that ATS use is associated with deficient dorsal striatal morphology which might reflect alterations in dopaminergic pathways. More importantly, these findings strongly suggest that even occasional, low-dose ATS use disrupts striatal integrity and cognitive functioning.

neuroscience↗