Biology subjects

Kendrick, K. M.

Publications and source records attributed to Kendrick, K. M..

36 records · Page 2Linked to original sources

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

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

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↗

bioRxiv2020

Putamen volume predicts real-time fMRI neurofeedback learning success across paradigms and neurofeedback target regions

Real-time fMRI guided neurofeedback training has gained increasing interest as a non-invasive brain regulation technique with the potential to normalize functional brain alterations in therapeutic contexts. Individual variations in learning success and treatment response have been observed, yet the neural substrates underlying the learning of self-regulation remain unclear. Against this background, we explored potential brain structural predictors for learning success with pooled data from three real-time fMRI datasets. Our analysis revealed that gray matter volume of the right putamen could predict neurofeedback learning success across the three datasets (n = 66 in total). Importantly, the original studies employed different neurofeedback paradigms during which different brain regions were trained pointing to a general association with learning success independent of specific aspects of the experimental design. Given the role of the putamen in associative learning the finding may reflect an important role of instrumental learning processes and brain structural variations in associated brain regions for successful acquisition of fMRI neurofeedback-guided self-regulation.

neuroscience↗

bioRxiv2020

Medial prefrontal activity at encoding determines recognition of threatening faces after 1.5 years

Studies demonstrated that faces with threatening emotional expressions are better remembered than non-threatening faces. However, whether this memory advantage persists over years and which neural systems underlie such an effect remains unknown. Here, we investigated recognition of incidentally encoded faces with angry, fearful, happy, sad and neutral expressions over >1.5 years (N= 89). Univariate analyses showed that threatening faces (angry, fearful) were better recognized than happy and neutral faces after >1.5 years, and that the threat-related memory enhancement was driven by forgetting of non-threatening faces. Multivariate principal component analysis (PCA) confirmed the discriminative performance between threatening and non-threatening faces. With an innovative Behavioral Pattern Similarity Analysis (BPSA) approach and functional magnetic resonance imaging (fMRI) acquisition during encoding, we further found that the long-term memory advantage for threatening faces were underpinned by differential neural encoding in the left inferior occipital gyrus (IOG) and right ventromedial prefrontal/orbitofrontal cortex (vmPFC/OFC). Our study provides the first evidence that threatening facial expressions lead to persistent face recognition over periods of >1.5 years and differential encoding-related activity in the visual cortex and medial prefrontal cortex may underlie this effect.

neuroscience↗

bioRxiv2020

Intrinsic connectivity of the prefrontal cortex and striato-limbic system respectively differentiate Major Depressive from Generalized Anxiety Disorder

Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) are highly prevalent and debilitating disorders. The high overlap on the symptomatic and neurobiological level led to ongoing debates about their diagnostic and neurobiological uniqueness. The present study aims to identify common and disorder-specific neuropathological mechanisms and treatment targets in MDD and GAD. The present study combined categorial and dimensional disorder models with a fully data-driven intrinsic network level analysis (Intrinsic Connectivity Contrast, ICC) to resting state fMRI data acquired in 108 partn = 35 and n = 38 unmedicated patients with first-episode GAD, MDD respectively and n=35 healthy controls). Convergent evidence from categorical and dimensional analyses revealed MDD-specific decreased whole-brain connectivity profiles of the medial prefrontal and dorsolateral prefrontal cortex while GAD was specifically characterized by decreased whole-brain connectivity profiles of the putamen and decreased communication of this region with the amygdala. Together, findings from the present data-driven analysis suggest that intrinsic communication of frontal regions engaged in executive functions and emotion regulation represent depression-specific neurofunctional markers and treatment targets whereas dysregulated intrinsic communication of the striato-amygdala system engaged in reinforcement-based and emotional learning processes represent GAD-specific markers and a promising treatment target.

neuroscience↗

bioRxiv2020

Oxytocinergic modulation of threat-specific amygdala sensitization in humans is critically mediated by serotonergic mechanisms

BackgroundOverarching conceptualizations propose that the complex social-emotional effects of oxytocin (OXT) in humans are partly mediated by interactions with other neurotransmitter systems. Recent animal models suggest that the anxiolytic effects of OXT are critically mediated by the serotonin (5-HT) system, yet direct evidence in humans is lacking. MethodsTo determine the role of 5-HT in OXT-induced attenuation of amygdala threat reactivity and sensitization/ desensitization, we conducted a parallel-group randomized placebo-controlled double-blind experiment during which n = 121 healthy subjects underwent a transient decrease in 5-HT signaling via acute tryptophan depletion (ATD, TRYP-) or the corresponding placebo-control protocols before the administration of intranasal OXT or placebo intranasal spray, respectively. Mean and repetition-dependent changes in threat-specific amygdala reactivity towards threatening stimuli (angry faces) as assessed by fMRI served as the primary outcome. ResultsNo treatment main or interaction effects on amygdala threat reactivity were observed, yet OXT switched bilateral amygdala threat sensitization to desensitization and this effect was significantly attenuated during decreased central 5-HT signaling via pretreatment with TRYP-. ConclusionsThe present findings provide the first evidence for a role of OXT in threat-specific amygdala desensitization in humans and suggest that these effects are critically mediated by the 5-HT system. OXT may have a therapeutic potential to facilitate amygdala desensitization and adjunct up-regulation of 5-HT neurotransmission may facilitate OXTs anxiolytic potential. The trial was preregistered on clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT03426176, ID NCT03426176)

neuroscience↗

bioRxiv2020

Intrinsic, dynamic and effective connectivity among large-scale brain networks modulated by oxytocin

The neuropeptide oxytocin is a key modulator of social-emotional behavior and its intranasal administration can influence the functional connectivity of brain networks involved in the control of attention, emotion and reward reported in humans. However, no studies have systematically investigated the effects oxytocin on dynamic or directional aspects of functional connectivity. The present study employed a novel computational framework to investigate these latter aspects in 15 oxytocin-sensitive regions using data from randomized placebo-controlled between-subject resting state functional MRI studies incorporating 200 healthy subjects. Results showed that oxytocin extensively modulated effective connectivity both between and within emotion, reward, salience and social cognition processing networks and their interactions with the default mode network, but had no effect on the frequency of dynamic changes. Top-down control over emotional processing regions such as the amygdala was particularly affected. Oxytocin effects were also sex-dependent, being more extensive in males. Overall, these findings suggest that modulatory effects of oxytocin on both within- and between-network interactions may underlie its functional influence on social-emotional behaviors, although in a sex-dependent manner. Furthermore, they demonstrate a useful approach to determining pharmacological influences on resting state effective connectivity and support oxytocins potential therapeutic use in psychiatric disorders.

neuroscience↗

bioRxiv2020

Oxytocin differentially modulates amygdala responses during top-down and bottom-up aversive anticipation

The ability to successfully regulate negative emotions such as fear and anxiety is vital for mental health. The neuropeptide oxytocin (OXT) acts as important modulator of emotion regulation, as reflected by reduced amygdala responses but increased amygdala-prefrontal cortex (PFC) functional connectivity in response to threatening stimuli. The present randomized, between-subject, placebo (PLC)-controlled pharmacological study combined intranasal administration of OXT with functional MRI during an explicit (cognitive) emotion regulation (i.e. distancing reappraisal) paradigm in 65 healthy male participants to investigate the modulatory effects of OXT on both bottom-up and top-down emotion regulation. OXT attenuated the activation in posterior insular cortex and amygdala during anticipation of top-down regulation of predictable threat stimuli in participants with high trait anxiety, providing evidence to support the anxiolytic action of OXT. In contrast, OXT enhanced amygdala activity during bottom-up anticipation of an unpredictable threat stimulus in participants with low trait anxiety. OXT may thus facilitate top-down goal-directed attention by attenuating amygdala activity in high anxiety individuals, while promote bottom-up attention/vigilance to unexpected threat by enhancing anticipatory amygdala activity in low anxiety individuals. The opposite effects of OXT on anticipatory amygdala activation in high versus low anxiety individuals may suggest a baseline anxiety level dependent mechanism via which OXT promotes optimal levels of amygdala activation during the anticipation of an imminent threat. OXT may thus have the potential to promote an adaptive balance between bottom-up and top-down attention systems depending on individual levels of pre-treatment trait anxiety levels.

neuroscience↗

bioRxiv2020

Emotional contagion of pain across different social cues shares common and process-specific neural representations

Insular and anterior cingulate cortex activation across vicarious pain induction procedures suggests that they are core pain empathy nodes. However, pain empathic responses encompass emotional contagion as well as unspecific arousal and overlapping functional activations are not sufficient to determine shared and process-specific neural representations. We employed multivariate pattern analyses to fMRI data acquired during physical and affective vicarious pain induction and found spatially and functionally similar cross-modality (physical versus affective) whole-brain vicarious pain-predictive patterns. Further analyses consistently identified shared neural representations in the bilateral mid-insula. Mid-insula vicarious pain patterns were not sensitive to capture non-painful arousing negative stimuli but predicted self-experienced pain during thermal stimulation, suggesting process-specific representation of emotional contagion for pain. Finally, a domain-general vicarious pain pattern which predicted vicarious as well as self-experienced pain was developed. Our findings demonstrate a generalizable neural expression of vicarious pain and suggest that the mid-insula encodes emotional contagion for pain.

neuroscience↗

bioRxiv2019

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

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

neuroscience↗

bioRxiv2019

Inter-subject phase synchronization differentiates neural networks underlying physical pain empathy

Recent approaches for understanding the neural basis of pain empathy emphasize the dynamic construction of neural networks underlying this multifaceted social cognitive process. Inter-subject phase synchronization (ISPS) is an approach for exploratory analysis of task-based fMRI data that reveals brain networks dynamically synchronized to task-features across participants. We applied ISPS to task-fMRI data assessing vicarious pain empathy in a large sample of healthy participants (n=238). The task employed physical (limb) and affective (faces) painful and corresponding non-painful visual stimuli. ISPS revealed two distinct networks synchronized during physical pain observation, one encompassing anterior insula and midcingulate regions strongly engaged in (vicarious) pain, and another encompassing parietal and inferior frontal regions associated with social cognitive processes which may further modulate and support the physical pain empathic response. No robust network synchronization was observed while processing affective pain, possibly reflecting high inter-individual variation in response to socially transmitted pain experiences. ISPS also revealed networks related to task onset or general processing of physical (limb) or affective (face) stimuli which encompassed networks engaged in object manipulation or face processing, respectively. Together, the ISPS approach permits segregation of networks engaged in different psychological processes, providing additional insight into shared neural mechanisms of empathy for physical pain, but not affective pain, across individuals.

neuroscience↗

bioRxiv2019

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

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

neuroscience↗

bioRxiv2018

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

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

genetics↗