Biology subjects

Tobler, P. N.

Publications and source records attributed to Tobler, P. N..

14 recordsLinked to original sources

bioRxiv2026

Neural mechanisms of self-conformity

We conform not only to the opinions and behaviors of others but also to those of ourselves, suggesting that the motivation to appear consistent leads us to treat ourselves like others. However, the neural mechanisms of self-conformity remain unclear. We used a sequential facial attractiveness-rating task with ostensible reminders of participants own previous ratings to investigate self-conformity and compare it against group conformity. Rating data showed that participants on average conformed to both themselves and the group. While some individuals conformed excessively (over-conformity), others went against their previous behavior (anti-conformity), similarly in self and group conditions. Neurally, dorsomedial and ventrolateral prefrontal cortex activity correlated with both self- and group conformity. Moreover, self-versus group conformity engaged more medial versus lateral prefrontal regions, and over-versus anti-conformity more ventral versus dorsal regions. These results suggest that self- and group conformity rely on both common and dedicated neural mechanisms.

neuroscience↗

bioRxiv2025

Distinct roles of neuronal phenotypes during neurofeedback adaptation

Learning adaptation allows the brain to refine motor patterns in response to changing environments rapidly. While population-level neural dynamics and single-neuron activity in motor learning have been widely studied, the contributions of individual neuron types remain poorly understood. Here, we employed a brain-machine interface (BMI) task with perturbations of varying difficulty to investigate single-neuron dynamics underlying neurofeedback adaptation in two rhesus macaques. Cortical neurons were classified based on waveform shape into narrow waveform (NW) and broad waveform (BW) categories, representing putative inhibitory interneurons and excitatory pyramidal neurons, respectively. Compared to BW neurons, NW neurons were more active and more strongly involved in the learning process. Moreover, task difficulty modulated neural responsiveness and coordination within both neuron groups, highlighting differential neuron engagement during motor learning. Our findings provide novel insights into single-neuron mechanisms underlying neurofeedback adaptation and emphasize the distinct functional roles of neuronal phenotypes in rapid learning processes. Author SummaryUnderstanding how the brain adapts to changes is crucial for improving treatments for neurological disorders and enhancing brain-machine interface (BMI) technology, which allows control of external devices using neural signals. In our study, we investigated how different types of brain cells contribute to the adaptation process when individuals encounter unexpected challenges during neurofeedback tasks. We discovered that one type of neuron was notably more active and played a more engaged role in rapidly adjusting neural activity compared to another type. These neurons demonstrated stronger coordination in their activity and showed greater responsiveness as the task difficulty increased. Our findings highlight the distinct roles of specific neurons in quickly adapting to neurofeedback tasks, offering insights that could enhance therapies for movement disorders and improve the precision and reliability of brain-controlled prosthetics.

neuroscience↗

bioRxiv2025

Population-level constraints on single neuron tuning changes during behavioral adaptation

In neurofeedback training, select neurons - of the billions that comprise the brain - are able to adapt their activity to produce a desired behavior, even though the feedback signal is low-dimensional. However, the extent that individual neurons are able to alter their activity within the context of the neurofeedback population is unclear. Using a brain-computer interface in monkeys (n=2; Macaca mulatta), we tested how the tuning of individual neurons changed in response to various feedback perturbations. Overall, we found that neurons that co-varied their activity the most with the population and those that contributed most to the behavior prior to the perturbation were most resistant to change- regardless of perturbation type. The degree to which individual neurons counteracted the applied perturbation explained daily differences in how well neurons collectively produced adapted behavior. Our work provides important insight into how population-level constraints impact the ability of individual neurons to adapt and support behavioral flexibility.

bioengineering↗

bioRxiv2024

Volitional Regulation and Transferable Patterns of Midbrain Oscillations

Dopaminergic brain areas are crucial for cognition and their dysregulation is linked to neuropsychiatric disorders typically treated with pharmacological interventions. These treatments often have side effects and variable effectiveness, underscoring the need for alternatives. We introduce the first demonstration of neurofeedback using local field potentials (LFP) from the ventral tegmental area (VTA). This approach leverages the real-time temporal resolution of LFP and ability to target deep brain. In our study, non-human primates learned to regulate VTA beta power using a customized normalized metric to stably quantify VTA LFP signal modulation. The subjects demonstrated flexible and specific control with different strategies for specific frequency bands, revealing new insights into the plasticity of VTA neurons contributing to oscillatory activity that is functionally relevant to many aspects of cognition. Excitingly, the subjects showed transferable patterns, a key criterion for clinical applications beyond training settings. This work provides a foundation for neurofeedback-based treatments, which may be a promising alternative to conventional approaches and open new avenues for understanding and managing neuropsychiatric disorders. Significance statementThis study demonstrates, for the first time, that neurofeedback using local field potentials (LFP) from the ventral tegmental area (VTA) is feasible in non-human primates. By leveraging the temporal resolution and ability to target deep brain regions, this approach provides a novel way to modulate brain activity linked to dopamine-related functions. The findings reveal that subjects can flexibly control VTA LFP signals and transfer learned strategies to new settings, offering potential for developing neurofeedback-based treatments. This research opens new avenues for managing neuropsychiatric disorders, presenting an alternative to traditional pharmacological interventions that often have side effects and limited effectiveness. The study highlights the plasticity of VTA neurons and their relevance to cognition and mood regulation.

neuroscience↗

bioRxiv2024

Social risk coding by amygdala activity and connectivity with dorsal anterior cingulate cortex

Risk is a fundamental factor affecting individual and social economic decisions, but its neural correlates are largely unexplored in the social domain. The amygdala, together with the dorsal anterior cingulate cortex (dACC), is thought to play a central role in risk taking. Here, we investigated in human volunteers (n=20; 11 females) how risk (defined as variance of reward probability distributions) in a social situation affects decisions and concomitant neural activity as measured with fMRI. We found social variance-risk signals in the amygdala. Activity in lateral parts of the amygdala increased parametrically with social reward variance of the presented options. Behaviorally, 75% of participants were averse to social risk as estimated in a Becker-DeGroot-Marschak auction-like procedure. The stronger this aversion, the more negative was the coupling between risk-related amygdala regions and dACC. This negative relation was significant for social risk attitude but not for the attitude towards variance-risk in juice outcomes. Our results indicate that the amygdala and its coupling with dACC process objective and subjectively evaluated social risk. Moreover, while social risk can be captured with a framework originally established by finance theory for individual risk, the amygdala appears to processes social risk largely separately from individual risk.

neuroscience↗

bioRxiv2022

A Process Model Account of the Role of Dopamine in Intertemporal Choice

Theoretical accounts disagree on the role of dopamine in intertemporal choice and assume that dopamine either promotes delay of gratification by increasing the preference for larger rewards or that dopamine reduces patience by enhancing the sensitivity to waiting costs. Here, we reconcile these conflicting accounts by providing empirical support for a novel process model according to which dopamine contributes to two dissociable components of the decision process, evidence accumulation and starting bias. We re-analyzed a previously published data set where intertemporal decisions were made either under the D2 antagonist amisulpride or under placebo by fitting a hierarchical drift diffusion model that distinguishes between dopaminergic effects on the speed of evidence accumulation and the starting point of the accumulation process. Blocking dopaminergic neurotransmission not only strengthened the sensitivity to whether a reward is perceived as worth the delay costs during evidence accumulation (drift rate) but also attenuated the impact of waiting costs on the starting point of the evidence accumulation process (bias). Taken together, our findings support a novel, process-based account of the role of dopamine for cost-benefit decision making, highlight the potential benefits of process-informed analyses and advance our understanding of dopaminergic contributions to decision making.

neuroscience↗

bioRxiv2022

Cerebellar and cortico-striatal-midbrain contributions to reward-cognition processes and apathy within the psychosis continuum

Negative symptoms in the psychosis continuum are linked to impairments in reward processing and cognitive function. Processes at the interface of reward processing and cognition and their relation to negative symptoms remain little studied, despite evidence suggestive of integration in mechanisms and neural circuitry. Here, we investigated brain activation during reward-dependent modulation of working memory (WM) and their relationship to negative symptoms in subclinical and early stages of the psychosis continuum. We included 27 persons with high schizotypal personality traits and 23 patients with first episode psychosis as well as 27 healthy controls. Participants underwent functional magnetic resonance imaging while performing an established 2-back WM task with two reward levels (5 CHF vs. no reward), which allowed us to assess common reward-cognition regions through whole-brain conjunction analyses and to investigate relations with clinical scores of negative symptoms. As expected for behavior, reward facilitated performance while cognitive load diminished it. At the neural level, the conjunction of high reward and high cognitive load contrasts across the psychosis continuum showed increased hemodynamic activity in the thalamus and the cerebellar vermis. During high cognitive load, more severe apathy but not diminished expression in the psychosis continuum was associated with reduced activity in right lateral orbitofrontal cortex, midbrain, posterior vermal cerebellum, caudate and lateral parietal cortex. Our results suggest that hypoactivity in the cerebellar vermis and the cortical-striatal-midbrain-circuitry in the psychosis continuum relates to apathy possibly via impaired flexible cognitive resource allocation for effective goal pursuit.

neuroscience↗

bioRxiv2021

Learning from ingroup experiences changes intergroup impressions

Living in multicultural societies, humans form impressions towards individuals of their own social groups (ingroup members) and of different social groups (outgroup members). Some psychological theories predict that intergroup impressions are mainly shaped by experiences with outgroup individuals ("outgroup focused theories"), while other theories predict that ingroup experiences play a dominant role ("ingroup focused theories"). Here we test predictions from these two psychological theories by estimating how intergroup impressions are dynamically shaped when people learn from both ingroup and outgroup experiences. Participants expected to receive painful shocks but were saved from pain by different ingroup or outgroup members in 75% of all trials. We measured neural responses using functional magnetic resonance imaging (fMRI), and participants rated their social closeness as well as impressions towards the ingroup and the outgroup. Behavioral results showed an initial ingroup bias in impression ratings which was significantly reduced over the course of learning. Computational learning models revealed that these changes in intergroup impressions were predicted by the weight given to ingroup prediction errors. The weight of the ingroup prediction error and its effect on intergroup impression change was stronger the more individuals identified with their ingroup. On the neural level, the left inferior parietal lobule (IPL) encoded more negative prediction errors for the ingroup compared to the outgroup. Moreover, stronger weight for ingroup prediction errors was related to increased neural coupling between the left IPL and the anterior insula (AI). This coupling further predicted learning-related changes in intergroup impressions. Together, our work provides computational and neural evidence for "ingroup focused theories", highlighting the importance of ingroup experiences in shaping social impressions in intergroup settings.

neuroscience↗

bioRxiv2021

Comparing adaptive coding of reward in bipolar I disorder and schizophrenia

BackgroundDeficits in neural processing of reward have been described in both bipolar disorder (BD) and schizophrenia (SZ), but it remains unclear to what extent these deficits are caused by similar mechanisms. Efficient reward processing relies on adaptive coding which allows representing large input spans by limited neuronal encoding ranges. Deficits in adaptive coding of reward have previously been observed across the SZ spectrum and correlated with total symptom severity. In the present work we sought to establish whether adaptive coding is similarly affected in patients with BD. Methods25 patients with BD, 27 patients with SZ and 25 healthy controls performed a variant of the Monetary Incentive Delay task during functional magnetic resonance imaging in two reward range conditions. ResultsAdaptive coding was impaired in BD and SZ in the posterior part of the right caudate. In contrast, BD did not show impaired adaptive coding in the anterior caudate and right precentral gyrus/insula, where SZ showed deficits compared to healthy controls. ConclusionsBD patients show adaptive coding deficits, that are similar to those observed in SZ in the right posterior caudate. Adaptive coding in BD appeared more preserved as compared to SZ participants especially in the more anterior part of the right caudate and to a lesser extent also in the right precentral gyrus. Thus, dysfunctional adaptive coding could constitute a fundamental deficit in severe mental illnesses that extends beyond the schizophrenia spectrum.

neuroscience↗

bioRxiv2021

Opioid antagonism reduces wanting by strengthening frontostriatal connectivity

Goal-directed behavior depends on both motivational ("wanting") and hedonic ("liking") dimensions of rewards. Previous animal and human research linked wanting and liking to anatomically and neurochemically distinct brain mechanisms, but it remains unknown as to how the different brain regions and neurotransmitter systems interact in processing distinct reward dimensions. Here, we assessed how pharmacological manipulations of opioid and dopamine receptor activation modulate the neural processing of wanting and liking in humans in a randomized, placebo-controlled, double-blind clinical trial. Blocking opioid receptor activation with naltrexone selectively reduced wanting of rewards, which on a neural level was reflected by stronger coupling between dorsolateral prefrontal cortex and the striatum under naltrexone compared with placebo. Our findings thus provide insights into how opioid receptors mediate frontostriatal gating of specifically motivational, not hedonic, aspects of rewards.

neuroscience↗

bioRxiv2021

Neural correlates of individual differences in aversion to risk and choice inconsistencies

AO_SCPLOWBSTRACTC_SCPLOWWhen making financial choices, most people prefer smaller but more certain gains to larger but more uncertain ones with the same expected value (risk aversion). However, attitudes toward risk may vary greatly also within individuals (choice inconsistency). To examine the brain dynamics implementing risky and inconsistent decisions, we recorded event-related brain potentials (ERPs) from 24 adults engaged in a task requiring choices between certain but smaller gains and uncertain but larger ones. Choice consistency and risk aversion were quantified for each individual. Participants were classified into three groups according to their attitude toward risk. Relative neutrality to risk was accompanied by a higher consistency across trials than risk aversion or proneness. Choice consistency was related to the amplitude of the positive ERP peaking near 200 ms after stimulus onset (P200), while risk aversion was related to modulation of the medial frontal negativity (MFN) and to the amplitude of a late positive potential (LPP). Late ERP activity was related to the modulation of value signals by risk levels and associated with individual differences in behavior. Overall, this study suggests that individual differences in attitude toward risk and choice consistency are associated with distinct brain dynamics.

neuroscience↗

bioRxiv2020

Increased random exploration in schizophrenia is associated with inflammation

One aspect of goal-directed behavior, which is known to be impaired in patients with schizophrenia (SZ), is balancing between exploiting a familiar choice with known reward value and exploring a lesser known but potentially more rewarding option. Despite its relevance to several symptom domains of SZ, this has received little attention in SZ research. In addition, while there is increasing evidence that SZ is associated with chronic low-grade inflammation, few studies have investigated how this relates to specific behaviors, such as balancing exploration and exploitation. We therefore assessed behaviors underlying the exploration-exploitation trade-off using a three-armed bandit task in 45 patients with SZ and 19 healthy controls (HC). This task allowed us to dissociate goal-unrelated (random) from goal-related (directed) exploration and correlate them with psychopathological symptoms. Moreover, we assessed a broad range of inflammatory proteins in the blood and related them to bandit task behavior. We found that, compared to HC, patients with SZ showed reduced task performance. This impairment was due to a shift from exploitation to random exploration, which was associated with symptoms of disorganization. Relative to HC, patients with SZ showed a pro-inflammatory blood profile. Furthermore, high sensitivity C-reactive protein (CRP) positively correlated with random exploration, but not with directed exploration or exploitation. In conclusion, we show that low-grade inflammation in patients with SZ is associated with random exploration, which can be considered a behavioral marker for disorganization. CRP may constitute a marker for severity of, and a potential treatment target for maladaptive exploratory behaviors.

molecular biology↗

bioRxiv2019

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↗

bioRxiv2019

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

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

neuroscience↗