Biology subjects

Hurlemann, R.

Publications and source records attributed to Hurlemann, R..

15 recordsLinked to original sources

bioRxiv2026

A neurofunctional signature of romantic love predicts rewards on social media, effects of oxytocin and drug-cue reactivity

Romantic love is a selective motivational state supporting pair bonding, yet its neural representation and relation to other affiliative-rewarding experiences remain unclear. Across eight fMRI studies (n=420) spanning naturalistic affiliative-reward, pharmacological and addiction-relevant experiments, we developed and evaluated multivariate whole-brain decoders of romantic love and friendship. Both signatures engaged mesocorticolimbic reward systems and the precuneus, yet were dissociable at the whole-brain level and in their recruitment of social-cognitive systems. The love signature generalized to reward on social media, was specific to positive valence, and did not track sweet-taste or monetary reward, indicating a distinct social-affiliative reward representation. Oxytocin selectively increased love - but not friendship - signature reactivity to the romantic partner. In an independent drug-cue-reactivity dataset, the love signature specifically identified heavy cannabis users. These findings establish a dissociable neurofunctional signature of romantic love in conserved bonding circuits that extend to digital affiliation and are co-opted in addiction.

neuroscience↗

bioRxiv2024

Oxytocin facilitates social behavior of female rats via selective modulation of interneurons in the medial prefrontal cortex

The hypothalamic neuropeptide oxytocin is best known for its prosocial behavioral effects. However, the precise anatomical and cellular targets for oxytocin in the cortex during social behavior remain elusive. Here we show that oxytocin neurons project directly to the medial prefrontal cortex where evoked axonal oxytocin release facilitates social behaviors in adult female rats. In conjunction, we report that local oxytocin receptor-expressing (OTR+) cells are predominantly interneurons, whose activation promotes social interaction. Notably, this prosocial effect persists even under physiological challenge (hunger), pointing to a dedicated prosocial circuit capable of overriding primary survival drives. We further demonstrate that activation of these OTR+ interneurons inhibits principal cells specifically projecting to the basolateral amygdala, thus providing a putative mechanism of selective oxytocin action in this sociability-promoting cortical network.

neuroscience↗

bioRxiv2022

Investigation of whether oxytocin and trust play a role in placebo effects of marketing actions

Expectations about the quality of a medical treatment influence how much an inert treatment helps to improve patient well-being. Similarly, expectations about the quality of products influence how identical goods and services are evaluated differently after their consumption. One driver for such "placebo effects" in medical treatments is social cognition in the form of trust, which may be influenced by the hormone oxytocin. An open question is whether trust and oxytocin play similar roles in marketing placebo effects. To answer this question, we combined oxytocin administration (24 IU) and trust questionnaires in a pre-registered double-blind randomized between-subjects study design (Nfood tasting task = 223; Ncognitive performance task = 202). We could not find evidence that oxytocin and trust play a role in placebo effects of marketing actions. Together with other recent null findings from oxytocin administration studies, these findings question the role trust might play in different types of placebo effects.

neuroscience↗

bioRxiv2022

Functional dissection of neural connectivity in generalized anxiety disorder

Differences in the correlated activity of networked brain regions have been reported in individuals with generalized anxiety disorder (GAD) but an overreliance on the null-hypothesis significance testing (NHST) framework limits the identification and characterization of disorder-relevant relationships. In this preregistered study, we applied a Bayesian statistical framework as well as NHST to the analysis of resting-state fMRI scans from females with GAD and demographically matched healthy comparison females. Eleven a-priori hypotheses about functional correlativity (FC) were evaluated using Bayesian (multilevel model) and frequentist (t-test) inference. Reduced FC between the ventromedial prefrontal cortex (vmPFC) and the posterior-mid insula (PMI) was confirmed by both statistical approaches. FC between the vmPFC-anterior insula, the amygdala-PMI, and the amygdala-dorsolateral prefrontal cortex (dlPFC) region pairs did not survive multiple comparison correction using the frequentist approach. However, the Bayesian model provided evidence for these region pairs having decreased FC in the GAD group. Leveraging Bayesian modeling, we demonstrate decreased FC of the vmPFC, insula, amygdala, and dlPFC in females with GAD. Exploiting the Bayesian framework revealed FC abnormalities between region pairs excluded by the frequentist analysis, as well as other previously undescribed regions, demonstrating the benefits of applying this statistical approach to resting state FC data.

neuroscience↗

bioRxiv2021

Estradiol and oxytocin modulate sex differences in hippocampal reactivity and episodic memory

Considerable evidence supports sex differences in episodic memory, which may translate to heightened vulnerability to stress- and trauma-related disorders in women. The hormones estradiol and oxytocin both affect episodic memory, but possible underlying hormonal interactions have not been systemically tested in humans. To this end, healthy women (n = 111) and men (n = 115) received estradiol gel (2 mg) or placebo before the administration of intranasal oxytocin (24 IU) or placebo in a randomized, placebo-controlled, parallel-group functional magnetic resonance imaging (fMRI) study. In the fMRI session, participants viewed positive, neutral, and negative scenes. A surprise recognition task was conducted three days later. Under placebo, women showed a significantly better recognition memory and increased hippocampal responses to subsequently remembered items independent of the emotional valence compared to men. The separate treatments with either hormone significantly diminished this mnemonic sex difference and reversed the hippocampal activation pattern. However, the combined treatments led to a memory performance comparable to that of the placebo group. Collectively, the results suggest that both hormones play a crucial role in modulating sex differences in episodic memory. Furthermore, possible antagonistic interactions between estradiol and oxytocin could explain previously observed opposing hormonal effects in women and men.

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

Alone Again: Altered Activation in the Observation Execution System during Synchronization in High Loneliness Individuals

1AO_SCPLOWBSTRACTC_SCPLOWLonely people evaluate social exchanges negatively and display difficulties in interactions. Interpersonal synchronization is crucial for achieving positive interactions, promoting affinity, closeness, and satisfaction. However, little is known about lonely individuals ability to synchronize and about their brain activity while synchronizing. Following the screening of 303 participants we recruited 32 low and 32 high loneliness participants. They were scanned while engaged in movement synchronization, using a novel dyadic interaction paradigm. Results showed that high loneliness individuals exhibited a reduced ability to adapt their movement to their partners movement. Intriguingly, during movement adaptation periods, high loneliness individuals showed increased activation in the observation-execution (OE) system, specifically in the inferior frontal gyrus and the inferior parietal lobule. They did not show increased activation in the dorsomedial prefrontal cortex, which in the context of synchronization was suggested to be related to gap-monitoring. Based on these findings, we propose a model according to which lonely people may require stronger activation of their OE system for alignment, to compensate for some deficiency in their synchronization ability. Despite this hyper-activation, they still suffer from reduced synchronization capacity. Consequently, synchronization may be a relevant intervention area for the amelioration of chronic loneliness.

neuroscience↗

bioRxiv2021

Loneliness and the social brain: how perceived social isolation impairs human interactions

Loneliness is a painful condition associated with increased risk for premature mortality. The formation of new, positive social relationships can alleviate feelings of loneliness, but requires rapid trustworthiness decisions during initial encounters and it is still unclear how loneliness hinders interpersonal trust. Here, we use a multimodal approach including behavioral, psychophysiological, hormonal, and neuroimaging measurements to probe a trust-based mechanism underlying impaired social interactions in loneliness. Pre-stratified healthy individuals with high loneliness scores (n = 42 out of a screened sample of 3678 adults) show reduced oxytocinergic and affective responsiveness to a positive conversation, report less interpersonal trust, and prefer larger social distances compared to controls (n = 40). Moreover, lonely individuals are rated as less trustworthy compared to controls and identified by the blinded confederate better than chance. During initial trust decisions, lonely individuals exhibit attenuated limbic and striatal activation and blunted functional connectivity between the anterior insula and occipitoparietal regions, which correlates with the diminished affective responsiveness to the positive social interaction. This neural response pattern is not mediated by loneliness-associated psychological symptoms. Thus, our results indicate compromised integration of trust-related information as a shared neurobiological component in loneliness, yielding a reciprocally reinforced trust bias in social dyads.

neuroscience↗

bioRxiv2020

A neural mechanism of social responsibility

This study investigated the neural mechanisms involved in feelings of interpersonal guilt and responsibility evoked by social decisions. In two studies (one during fMRI), participants repeatedly chose between safe and risky monetary outcomes in social contexts. Across conditions, each participant chose for both themselves and a partner (Social condition), or the partner chose for both themselves and the participant (Partner condition), or the participant chose just for themselves (Solo condition, control). If the risky option was chosen in the Social or Partner condition, participant and partner could each receive either the high or the low outcome of a lottery with 50% probability, independently of each other. Participants were shown the outcomes for themselves and for their partner on each trial, and reported their momentary happiness every few trials. As expected, participant happiness decreased following both low lottery outcomes for themselves and for the partner. Crucially, happiness decreases following low outcomes for the partner were larger when the participant rather than their partner had made the choice, which fits an operational definition of guilt. This guilt effect was associated with BOLD signal increase in the left anterior insula. Connectivity between this region and the right inferior frontal gyrus varied depending on choice and experimental condition, suggesting that this part of prefrontal cortex is sensitive to guilt-related information during social choices. Variations in happiness were well explained by computational models based on participants and partners rewards and reward prediction errors. A model-based analysis revealed a left superior temporal sulcus cluster that tracked partner reward prediction errors that followed participant choices. Our findings identify neural mechanisms of guilt and social responsibility during social decisions under risk.

neuroscience↗

bioRxiv2019

Cue-reactivity in the ventral striatum characterizes heavy cannabis use, whereas reactivity in the dorsal striatum mediates dependent use

BackgroundAnimal models of addiction suggest that the transition from incentive-driven to habitual and ultimately compulsive drug use is mediated by a shift from ventral to dorsal striatal cue-control over drug seeking. Previous studies in human cannabis users reported elevated trait impulsivity and cue-reactivity in striatal circuits, however, these studies were not able to separate addiction-related from exposure-related adaptations.\n\nMethodsTo differentiate the adaptive changes, the present functional magnetic resonance imaging study examined behavioral and neural cue-reactivity in dependent (n = 18) and non-dependent (n = 20) heavy cannabis users and a non-using reference group (n = 44).\n\nResultsIrrespective of dependence status, cannabis users demonstrated elevated trait impulsivity as well as increased ventral striatal reactivity and striato-frontal coupling in response to drug cues. Dependent users selectively exhibited dorsal-striatal reactivity and decreased striato-limbic coupling during cue-exposure. An exploratory analysis revealed that higher ventral caudate cue-reactivity was associated with stronger cue-induced arousal and craving in dependent users, whereas this pattern was reversed in non-dependent users.\n\nConclusionsTogether the present findings suggest that an incentive sensitization of the ventral striatal reward system may promote excessive drug use in humans, whereas adaptations in dorsal striatal systems engaged in habit formation may promote the transition to addictive use.

neuroscience↗

bioRxiv2018

Impaired cognitive performance under psycho-social stress in cannabis dependence is mediated by attenuated precuneus activity

BackgroundDeficient regulation of stress plays an important role in the escalation of substance use, addiction and relapse. Accumulating evidence suggests dysregulations in cognitive and reward-related processes and the underlying neural circuitry in cannabis dependence. However, despite the important regulatory role of the endocannabinoid system in the stress response, associations between chronic cannabis use and altered stress processing on the neural level have not been systematically examined. MethodsAgainst this background, the present functional magnetic resonance imaging (fMRI)study examined psycho-social stress processing in cannabis-dependent males (n = 28) and matched controls (n = 23) using an established stress-induction paradigm (Montreal Imaging Stress Task) that combines computerized (adaptive) mental arithmetic challenges with social evaluative threat. ResultsDuring psycho-social stress exposure, but not the no-stress condition, cannabis users demonstrated impaired performance relative to controls. In contrast, levels of experienced stress and cardiovascular stress responsivity did not differ from controls. Functional MRI data revealed that stress-induced performance deteriorations in cannabis users were accompanied by decreased precuneus activity and increased connectivity of this region with the dorsal medial prefrontal cortex. LimitationsOnly male cannabis-dependent users were examined, the generalizability in female users remains to be determined. ConclusionTogether, the present findings provide first evidence for exaggerated stress-induced cognitive performance deteriorations in cannabis users. The neural data suggest that deficient stress-related dynamics of the precuneus may mediate the deterioration of performance on the behavioral level.

neuroscience↗

bioRxiv2018

Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of adult major depressive episodes: A systematic review and network meta-analysis of 113 randomised clinical trials

Background: Non-surgical brain stimulation techniques have been applied as tertiary treatments in major depression. However, the relative efficacy and acceptability of individual protocols is uncertain. Our aim was to estimate the comparative clinical efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults.\n\nMethods: Embase, PubMed/MEDLINE and PsycINFO were searched up until May 8, 2018, supplemented by manual searches of bibliographies of recent reviews and included trials. We included clinical trials with random allocation to electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), accelerated TMS (aTMS), priming TMS (pTMS), deep TMS (dTMS), theta burst stimulation (TBS), synchronised TMS (sTMS), magnetic seizure therapy (MST) or transcranial direct current stimulation (tDCS) protocols or sham. Data were extracted from published reports and outcomes were synthesised using pairwise and network random-effects meta-analysis. Primary outcomes were response (efficacy) and all-cause discontinuation (acceptability). We computed odds ratios (OR) with 95% confidence intervals (CI). Remission and continuous post-treatment depression severity scores were also examined.\n\nResults: 113 trials (262 treatment arms) randomising 6,750 patients (mean age = 47.9 years; 59% female) with major depressive disorder or bipolar depression met our inclusion criteria. In terms of efficacy, 10 out of 18 treatment protocols were associated with higher response relative to sham in network meta-analysis: bitemporal ECT (OR=8.91, 95%CI 2.57-30.91), high-dose right-unilateral ECT (OR=7.27, 1.90-27.78), pTMS (OR=6.02, 2.21-16.38), MST (OR=5.55, 1.06-28.99), bilateral rTMS (OR=4.92, 2.93-8.25), bilateral TBS (OR=4.44, 1.47-13.41), low-frequency right rTMS (OR=3.65, 2.13-6.24), intermittent TBS (OR=3.20, 1.45-7.08), high-frequency left rTMS (OR=3.17, 2.29-4.37) and tDCS (OR=2.65, 1.55-4.55). Comparing active treatments, bitemporal ECT and high-dose right-unilateral ECT were associated with increased response. All treatment protocols were at least as acceptable as sham treatment.\n\nConclusion: We found that non-surgical brain stimulation techniques constitute viable alternative or add-on treatments for adult patients with major depressive episodes. Our findings also highlight the need to consider other patient and treatment-related factors in addition to antidepressant efficacy and acceptability when making clinical decisions; and emphasize important research priorities in the field of brain stimulation.\n\nO_LSTTreatment abbreviationsC_LSTECT = Electroconvulsive Therapy O_LIBF ECT = bifrontal ECT (1)\nC_LIO_LIBT ECT = bitemporal ECT (2)\nC_LIO_LIRUL ECT= right unilateral ECT O_LIH-RUL = high-dose RUL ECT (3)\nC_LIO_LILM-RUL = low to moderate-dose RUL ECT (4)\nC_LI\nC_LI\nrTMS = repetitive Transcranial Magnetic Stimulation O_LIHF-L rTMS = high-frequency rTMS of the left DLPFC (5)\nC_LIO_LIHF-R rTMS = high-frequency rTMS of the right DLPFC (6)\nC_LIO_LILF-R rTMS = low-frequency rTMS of the right DLPFC (7)\nC_LIO_LILF-L rTMS = low-frequency rTMS of the left DLPFC (8)\nC_LIO_LIBL rTMS = bilateral rTMS of the DLPFC (9)\nC_LI\ndTMS = deep Transcranial Magnetic Stimulation (10)\npTMS = priming Transcranial Magnetic Stimulation (11)\naTMS = accelerated Transcranial Magnetic Stimulation (12)\nsTMS = synchronised Transcranial Magnetic Stimulation (13)\nTBS = Theta Burst Stimulation O_LIiTBS = intermittent TBS of the left DLPFC (14)\nC_LIO_LIcTBS = continuous TBS of the right DLPFC (15)\nC_LIO_LIblTBS = bilateral TBS of the DLPFC (16)\nC_LI\nMST = Magnetic Seizure Therapy (17)\ntDCS = transcranial Direct Current Stimulation (18)\n\n\nKey points\n\nQuestion: What is the clinical efficacy and acceptability of non-surgical brain stimulation protocols for the acute treatment of major depressive episodes in adults?\n\nFindings: In this network meta-analysis, 10 out of 18 treatment protocols were associated with higher response rates relative to sham, most notably bitemporal and high-dose right unilateral electroconvulsive therapy. All treatment protocols were at least as acceptable as sham treatment.\n\nMeaning: Non-surgical brain stimulation techniques constitute viable alternative or add-on treatment strategies for adult patients with major depressive episodes.

neuroscience↗

bioRxiv2018

Oxytocin enhancement of emotional empathy: generalization across cultures and effects on amygdala activity

Accumulating evidence suggests that the neuropeptide oxytocin can enhance empathy although it is unclear which specific behavioral and neural aspects are influenced, and whether the effects are modulated by culture, sex and trait autism. Based on previous findings in Caucasian men, we hypothesized that a single intranasal dose of oxytocin would specifically enhance emotional empathy via modulatory effects on the amygdala in an Asian (Chinese) population and explored the modulatory role of sex and trait autism on the effects. We first conducted a double-blind, randomized between-subject design experiment using a modified version of the multifaceted empathy task (MET) to determine whether oxytocins facilitation of emotional empathy can be replicated in Chinese men (n = 60). To further explore neural mechanisms behind and potential sex differences, functional MRI and skin conductance measures were acquired in an independent experiment incorporating men and women (n = 72). Oxytocin enhanced emotional empathy across experiments and sex, an effect that was accompanied by reduced amygdala activity and increased skin conductance responses. On the network level oxytocin enhanced functional coupling of the right amygdala with the insula and posterior cingulate cortex for positive valence stimuli but attenuated coupling for negative valence stimuli. The effect of oxytocin on amygdala functional connectivity with the insula was modulated by trait autism. Overall, our findings provide further support for the role of oxytocin in facilitating emotional empathy and demonstrate that effects are independent of culture and sex and involve modulatory effects on the amygdala and its interactions with other key empathy regions.

neuroscience↗

bioRxiv2018

Shifted balance of dorsal versus ventral striatal communication with frontal reward and regulatory regions in cannabis dependence

The transition from voluntary to addictive behavior is characterized by a loss of regulatory control in favor of reward driven behavior. Animal models indicate that this process is neurally underpinned by a shift in ventral to dorsal striatal control of behavior, however this shift has not been directly examined in humans. Against this background the present resting state fMRI study employed a two-step approach to (1) precisely map striatal alterations using a novel, data-driven network classification strategy combining Intrinsic Connectivity Contrast (ICC) with Multivoxel Pattern Analysis (MVPA) and, (2) to determine whether a ventral to dorsal striatal shift in connectivity with reward and and regulatory control regions can be observed in abstinent (28 days) male cannabis-dependent individuals (n = 24) relative to matched controls (n = 28). Network classification revealed that the groups can be reliably discriminated by global connectivity profiles of two striatal regions that mapped onto the ventral (nucleus accumbens) and dorsal striatum (caudate). Subsequent functional connectivity analysis demonstrated a relative shift between ventral and dorsal striatal communication with fronto-limbic regions that have been consistently involved in reward processing (rostral ACC) and executive / regulatory functions (dorsomedial PFC). Specifically, in the cannabis dependent subjects connectivity between the ventral striatum with the rostral ACC increased, whereas both striatal regions were uncoupled from the regulatory dorsomedial PFC. Together these findings suggest a shift in the balance between dorsal and ventral striatal control in cannabis dependence. Similar changes have been observed in animal models and may promote the loss of control central to addictive behavior.

neuroscience↗

bioRxiv2018

Altered Reward Processing in Abstinent Dependent Cannabis Users: Social Context Matters

Public perception of cannabis as relatively harmless, alongside claimed medical benefits, have led to moves towards its legalization. Yet, long-term consequences of cannabis dependence, and whether they differ qualitatively from other drugs, are still poorly understood. A key feature of addictive drugs is that chronic use leads to adaptations in reward processing, blunting responsivity to the substance itself and other rewarding stimuli. Against this background, the present study investigated whether cannabis dependence is associated with reductions in hedonic representations by measuring behavioral and neural responses to social reward in 23 abstinent cannabis-dependent men and 24 matched non-using controls. In an interpersonal pleasant touch fMRI paradigm, participants were led to believe they were in physical closeness of or touched (CLOSE, TOUCH) by either a male or female experimenter (MALE, FEMALE), allowing the assessment of touch- and social context-dependent (i.e. female compared to male social interaction) reward dynamics.\n\nUpon female compared to male touch, dependent cannabis users displayed a significantly attenuated increase of reward experience compared to healthy controls. Controls responded to female as compared to male interaction with increased striatal activation whereas cannabis users displayed the opposite activation pattern, with stronger alterations being associated with a higher lifetime exposure to cannabis. Neural processing of pleasant touch in dependent cannabis users remained intact.\n\nThese findings demonstrate that cannabis dependence in men is linked to similar lasting neuroadaptations in striatal responsivity to hedonic stimuli as observed for other drugs of abuse. However, reward processing deficits seem to depend on the social context.

neuroscience↗