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Scharnowski, F.

Publications and source records attributed to Scharnowski, F..

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Neural Mechanisms of Feedback Processing and Behavioral Adaptation during Neurofeedback Training

The acquisition of new skills is facilitated by providing individuals with feedback that reflects their performance. This process creates a closed loop that involves feedback processing and regulation recalibration to promote effective training. Functional magnetic resonance imaging (fMRI)-based neurofeedback is unique in applying this principle by delivering direct feedback on the self-regulation of brain activity. Understanding how feedback-driven learning occurs requires examining how feedback is evaluated and how regulation adjusts in response to feedback signals. In this pre-registered mega-analysis, we re-analyzed data from eight intermittent fMRI neurofeedback studies (N = 153 individuals) to investigate brain regions where activity and connectivity are linked to feedback processing and regulation recalibration (i.e., regulation after feedback) during training. We harmonized feedback scores presented during training in these studies and computed their linear associations with brain activity and connectivity using parametric general linear model analyses. We observed that, during feedback processing, feedback scores were positively associated with (1) activity in the reward system, dorsal attention network, default mode network, and cerebellum; and with (2) reward system-related connectivity within the salience network. During regulation recalibration, no significant associations were observed between feedback scores and either activity or associative learning-related connectivity. Our results suggest that neurofeedback is processed in the reward system, supporting the theory that reinforcement learning shapes this form of brain training. In addition, the involvement of large-scale networks in feedback processing, continuously transitioning between evaluating external feedback and internally assessing the adopted cognitive state, suggests that higher-level processing is integral to this type of learning. Our findings highlight the pivotal role of performance-related feedback as a driving force in learning, potentially extending beyond neurofeedback training to other feedback-based processes. Key PointsWe conducted a pre-registered mega-analysis integrating data from eight fMRI neurofeedback studies to examine feedback processing and regulation recalibration during neurofeedback training. During feedback processing, feedback was associated with activity in the reward system, dorsal attention network, default mode network, and cerebellum; as well as with reward system-related connectivity within the salience network. We found no positive results during regulation blocks; however, additional analyses suggest that recalibration may have already occurred during feedback presentation.

neuroscience↗

SpiDa-MRI, behavioral and (f)MRI data of adults with fear of spiders

Neuroimaging has greatly improved our understanding of phobic mechanisms. To expand on these advancements, we present data on the heterogeneity of neural patterns in spider phobia combined with various psychological dimensions of spider phobia, using spider-relevant stimuli of various intensities. Specifically, we have created a database in which 49 spider-fearful individuals viewed 225 spider-relevant images in the fMRI scanner and performed behavioral avoidance tasks before and after the fMRI scan. For each participant, the database consists of the neuroimaging part, which includes an anatomical scan, 5 passive-viewing and 2 resting-state functional runs in both raw and pre-processed form along with associated quality control reports. Additionally, a behavioral section includes self-report questionnaires and avoidance tasks collected in pre- and post-sessions. The dataset is well suited for investigating neural mechanisms of phobias, brain-behavior correlations, and also contributes to the existing phobic neuroimaging datasets with spider-fearful samples. O_TBL View this table: org.highwire.dtl.DTLVardef@f76a39org.highwire.dtl.DTLVardef@15eeaa2org.highwire.dtl.DTLVardef@7e4f1borg.highwire.dtl.DTLVardef@7b78f1org.highwire.dtl.DTLVardef@413e78_HPS_FORMAT_FIGEXP M_TBL C_TBL

neuroscience↗

Decoding of resting-state using task-based multivariate pattern analysis supports the Incentive-Sensitization Theory in nicotine use disorder

BackgroundThe Incentive-Sensitization Theory postulates that addiction is primarily driven by the sensitization of the brains reward system to addictive substances, such as nicotine. According to this theory, exposure to such substances leads to an increase in wanting, while liking the experience remains relatively unchanged. Although this candidate mechanism has been well substantiated through animal brain research, its translational validity for humans has only been partially demonstrated so far, with evidence from human neuroscience data being very limited. MethodsFrom fMRI data of N=31 individuals with Nicotine Use Disorder, we created multivoxel patterns capable of capturing wanting and liking-related dimensions from a smoking cue-reactivity task. Using these patterns, we then designed a novel resting-state reading method to evaluate how much wanting or liking still persist as a neural trace after watching the cues. ResultsWe found that the persistence of wanting-related brain patterns at rest increases with longer smoking history but this was not the case for liking-related patterns. Interestingly, such behavior has not been observed for non-temporal measures of smoking intensity. ConclusionThis study provides basic human neuroscience evidence that the dissociation between liking and wanting escalates over time, further substantiating the Incentive-Sensitization Theory, at least for Nicotine Use Disorder. These results suggest that treatment approaches could be personalized to account for the variability in individuals neural adaptation to addiction by considering how individuals differ in the extent to which their incentive salience system is sensitized.

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Amygdala habituation during exposure is associated with failure to reduce phobic symptoms

Exposure therapy is an established treatment for anxiety disorders but the mechanisms underpinning its effectiveness remain unclear. Two theories offer contrasting perspectives: the traditional habituation model posits that a form of stimulus desensitization is required during exposure, while the inhibitory learning model emphasizes the formation of new non-fearful associations. Crucially, while the former may manifest as amygdala habituation, the latter may not. To distinguish between the two models, this study uses functional magnetic resonance imaging to examine the amygdala responses of spider-fearful participants during fear exposure. We hypothesized that intervention success might align with stable or even increased amygdala activation - an indicator of active engagement and re-learning as proposed by the inhibitory learning model. Conversely, decreasing amygdala activity might not be a sign of reduced fear memory as proposed by the habituation model, but could signal mental detachment, leading to suboptimal treatment outcomes. Our results corroborated our hypotheses: individuals with escalating amygdala responses during exposure exhibited better clinical progress, while those showing amygdala habituation benefited less. Our results strengthen the case for the inhibitory learning model and highlight that therapy may not aim to diminish fear per se but rather to engage patients in active processing and association formation.

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Towards fNIRS Hyperfeedback: A Feasibility Study on Real-Time Interbrain Synchrony

Social interaction is of fundamental importance to humans. Prior research has highlighted the link between interbrain synchrony and positive outcomes in human social interaction. Neurofeedback is an established method to train ones brain activity and might offer a possibility to increase interbrain synchrony. Consequently, it would be advantageous to determine the feasibility of creating a neurofeedback system for enhancing interbrain synchrony to benefit human interaction. In this study, we investigated whether the most widely employed metric for interbrain synchrony, namely wavelet transform coherence, can be assessed accurately in near real-time using functional near-infrared spectroscopy (fNIRS), which is recognized for its mobility and ecological suitability for interactive research. To this end, we have undertaken a comprehensive approach encompassing simulations and a re-evaluation of two human-interaction datasets. Our findings indicate the potential for a stable near real-time measurement of wavelet transform coherence for integration durations of about one minute. This would align well with the methodology of an intermittent neurofeedback procedure. Our investigation lays the technical foundation for an fNIRS-based system to measure interbrain synchrony in near real-time. This advancement is crucial for the future development of a neurofeedback training system tailored to enhance interbrain synchrony to potentially benefit human interaction.

neuroscience↗

Thalamic volume and functional connectivity are associated with nicotine dependence severity and craving

Tobacco smoking is associated with deleterious health outcomes. Most smokers want to quit smoking, yet relapse rates are high. Understanding neural differences associated with tobacco use may help generate novel treatment options. Several animal studies have recently highlighted the central role of the thalamus in substance use disorders, but this research focus has been understudied in human smokers. Here, we investigated associations between structural and functional magnetic resonance imaging measures of the thalamus and its subnuclei to distinct smoking characteristics. We acquired anatomical scans of 32 smokers as well as functional resting-state scans before and after a cue-reactivity task. Thalamic functional connectivity was associated with craving and dependence severity, whereas the volume of the thalamus was associated with dependence severity only. Craving, which fluctuates rapidly, was best characterized by differences in brain function, whereas the rather persistent syndrome of dependence severity was associated with both brain structural differences and function. Our study supports the notion that functional versus structural measures tend to be associated with behavioral measures that evolve at faster versus slower temporal scales, respectively. It confirms the importance of the thalamus to understand mechanisms of addiction and highlights it as a potential target for brain-based interventions to support smoking cessation, such as brain stimulation and neurofeedback.

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Pre- and post-task resting-state differs in clinical populations

Resting-state functional connectivity has generated great hopes as a potential brain biomarker for improving prevention, diagnosis, and treatment in psychiatry. This neuroimaging protocol can routinely be performed by patients and does not depend on the specificities of a task. Thus, it seems ideal for big data approaches that require aggregating data across multiple studies and sites. However, technical variability, diverging data analysis approaches, and differences in data acquisition protocols might introduce heterogeneity to the aggregated data. Besides these technical aspects, the psychological state of participants might also contribute to heterogeneity. In healthy participants, studies have shown that behavioral tasks can influence resting-state measures, but such effects have not yet been reported in clinical populations. Here, we fill this knowledge gap by comparing resting-state functional connectivity before and after clinically relevant tasks in two clinical conditions, namely substance use disorders and phobias. The tasks consisted of viewing craving-inducing and spider anxiety provoking pictures that are frequently used in cue-reactivity studies and exposure therapy. We found distinct pre- vs. post-task resting-state connectivity differences in each group, as well as decreased thalamo-cortical and increased intra-thalamic connectivity which might be associated with decreased vigilance in both groups. Notably, the pre- vs. post-task thalamus-amygdala connectivity change within a patient cohort seems more pronounced than the difference of that connection between the smoker vs. phobia clinical trait. Our results confirm that resting-state measures can be strongly influenced by changes in psychological states that need to be taken into account when pooling resting-state scans for clinical biomarker detection. This demands that resting-state datasets should include a complete description of the experimental design, especially when a task preceded data collection.

neuroscience↗

Long-term effects of network-based fMRI neurofeedback training for sustained attention

Neurofeedback allows for learning voluntary control over ones own brain activity, aiming to enhance cognition and clinical symptoms. A recent study improved sustained attention temporarily by training healthy participants to up-regulate the differential activity of the sustained attention network (SAN) minus the default mode network (DMN). However, long-term learning effects of functional magnetic resonance imaging (fMRI) neurofeedback training remain under-explored. Here, we evaluate the effects of network-based fMRI neurofeedback training for sustained attention by assessing behavioral and brain measures before, one day after, and two months after training. The behavioral measures include task as well as questionnaire scores, and the brain measures include activity and connectivity during self-regulation runs without feedback (i.e., transfer runs) and during resting-state runs. Neurally, we found that participants maintained their ability to control the differential activity during follow-up sessions. Further, exploratory analyses showed that the training-induced increase in FC between the DMN and occipital gyrus was maintained during follow-up transfer runs, but not during follow-up resting-state runs. Behaviorally, we found that enhanced sustained attention right after training returned to baseline level during follow-up. The discrepancy between lasting regulation-related brain changes but transient behavioral and resting-state effects raises the question of how neural changes induced by neurofeedback training translate to potential behavioral improvements. Since neurofeedback directly targets brain measures to indirectly improve behavior long-term, a better understanding of the brain-behavior associations during and after neurofeedback training is needed to develop its full potential as a promising scientific and clinical tool. Key pointsO_LIParticipants were still able to self-regulate the differential activity between large-scale networks two months after the end of neurofeedback training and this during transfer runs without feedback. C_LIO_LILasting brain changes were also observed in the functional connectivity of trained regions in runs during which participants engaged in active self-regulation as well as during resting-state runs without concomitant self-regulation. C_LIO_LIThe increased sustained attention we observed right after the end of neurofeedback training did not persist two months later. C_LI

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Can we predict real-time fMRI neurofeedback learning success from pre-training brain activity?

Neurofeedback training has been shown to influence behavior in healthy participants as well as to alleviate clinical symptoms in neurological, psychosomatic, and psychiatric patient populations. However, many real-time fMRI neurofeedback studies report large interindividual differences in learning success. The factors that cause this vast variability between participants remain unknown and their identification could enhance treatment success. Thus, here we employed a meta-analytic approach including data from 24 different neurofeedback studies with a total of 401 participants, including 140 patients, to determine whether levels of activity in target brain regions during pre-training functional localizer or no-feedback runs (i.e., self-regulation in the absence of neurofeedback) could predict neurofeedback learning success. We observed a slightly positive correlation between pre-training activity levels during a functional localizer run and neurofeedback learning success, but we were not able to identify common brain-based success predictors across our diverse cohort of studies. Therefore, advances need to be made in finding robust models and measures of general neurofeedback learning, and in increasing the current study database to allow for investigating further factors that might influence neurofeedback learning.

neuroscience↗

Individual differences in the mechanistic control of the dopaminergic midbrain

The dopaminergic midbrain is associated with brain functions, such as reinforcement learning, motivation and decision-making that are often disturbed in neuropsychiatric disease. Previous research has shown that activity in the dopaminergic midbrain can be endogenously modulated via neurofeedback, suggesting potential for non-pharmacological interventions. However, the robustness of endogenous modulation, a requirement for clinical translation, is unclear. Here, we examined how self-modulation capability relates to regulation transfer. Moreover, to elucidate potential mechanisms underlying successful self-regulation, we studied individual prediction error coding, and, during an independent monetary incentive delay (MID) task, individual reward sensitivity. Fifty-nine participants underwent neurofeedback training either in a veridical or inverted feedback group. Successful self-regulation was associated with post-training activity within the cognitive control network and accompanied by decreasing prefrontal prediction error signals and increased prefrontal reward sensitivity in the MID task. The correlative link of dopaminergic self-regulation with individual differences in prefrontal prediction error and reward sensitivity suggests that reinforcement learning contributes to successful self-regulation. Our findings therefore provide new insights in the control of dopaminergic midbrain activity and pave the way to improve neurofeedback training in neuropsychiatric patients.

neuroscience↗

The effects of psychiatric history and age on self-regulation of the default mode network

Real-time neurofeedback enables human subjects to learn to regulate their brain activity, effecting behavioral changes and improvements of psychiatric symptomatology. Neurofeedback up-regulation and down-regulation have been assumed to share common neural correlates. Neuropsychiatric pathology and aging incur suboptimal functioning of the default mode network. Despite the exponential increase in real-time neuroimaging studies, the effects of aging, pathology and the direction of regulation on neurofeedback performance remain largely unknown. Using open-access analyses and real-time fMRI data shared through the Rockland Sample Real-Time Neurofeedback project (N=136), we first modeled neurofeedback performance and learning in a group of subjects with psychiatric history (na=74) and a healthy control group (nb=62). Subsequently, we examined the relationship between up-regulation and down-regulation learning, the relationship between age and neurofeedback performance in each group and differences in neurofeedback performance between the two groups. Results show that in an initial session of default mode network neurofeedback with real-time fMRI, up-regulation and down-regulation learning scores are negatively correlated. Moreover, age correlates negatively with default mode network neurofeedback performance, only in absence of psychiatric history. Finally, adults with psychiatric history outperform healthy controls in default mode network up-regulation. Interestingly, the performance difference is related to no up-regulation learning in controls.

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Self-regulation of the Dopaminergic Reward Circuit in Cocaine Users with Mental Imagery and Neurofeedback

Background: Enhanced drug-related reward sensitivity accompanied by impaired sensitivity to non-drug related rewards in the mesolimbic dopamine system are thought to underlie the broad motivational deficits and dysfunctional decision-making frequently observed in cocaine use disorder (CUD). Effective approaches to modify this imbalance and reinstate non-drug reward responsiveness are urgently needed. Here we examine whether cocaine users (CU) can use mental imagery of non-drug rewards to self-regulate the ventral tegmental area and substantia nigra (VTA/SN). We expected that compulsive and obsessive thoughts about cocaine consumption would hamper the ability to self-regulate the VTA/SN. Finally, we tested if self-regulation of the VTA/SN can be improved with real-time fMRI (rtfMRI) neurofeedback (NFB).\n\nMethods: Twenty-two CU and 28 healthy controls (HC) were asked to voluntarily up-regulate VTA/SN activity with rewarding non-drug imagery alone, or combined with rtfMRI NFB of VTA/SN activity. Obsessive-compulsive drug use was measured with the Obsessive Compulsive Cocaine Use Scale (OCCUS).\n\nResults: CU were able to induce activity in the dopaminergic midbrain and other reward regions with reward imagery. The ability to self-regulate the VTA/SN was reduced in those with more severe obsessive-compulsive drug use. NFB enhanced the effect of non-drug imagery.\n\nConclusion: CU can voluntary activate their reward system through non-drug related imagery and improve this ability with rtfMRI NFB. Combining reward imagery and rtFMRI NFB has great potential for modifying the maladapted reward sensitivity and reinstating non-drug reward responsiveness. This motivates further work to examine the therapeutic potential of cognitive neurostimulation in CUD.

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