bioRxiv Subject Collection: Neuroscience's Journal
 
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Tuesday, March 12th, 2024

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    1:31a
    A Novel, Robust, and Portable Platform for Magnetoencephalography using Optically Pumped Magnetometers
    Magnetoencephalography (MEG) measures brain function via assessment of magnetic fields generated by neural currents. Conventional MEG uses superconducting sensors, which place significant limitations on performance, practicality, and deployment; however, the field has been revolutionised in recent years by the introduction of optically-pumped-magnetometers (OPMs). OPMs enable measurement of the MEG signal without cryogenics, and consequently the conception of OPM-MEG systems which ostensibly allow increased sensitivity and resolution, lifespan compliance, free subject movement, and lower cost. However, OPM-MEG remains in its infancy with limitations on both sensor and system design. Here, we report a new OPM-MEG design with miniaturised and integrated electronic control, a high level of portability, and improved sensor dynamic range (arguably the biggest limitation of existing instrumentation). We show that this system produces equivalent measures when compared to an established instrument; specifically, when measuring task-induced beta-band, gamma-band and evoked neuro-electrical responses, source localisations from the two systems were highly comparable and temporal correlation was >0.7 at the individual level and >0.9 for groups. Using an electromagnetic phantom, we demonstrate improved dynamic range by running the system in background fields up to 8 nT. We show that the system is effective in gathering data during free movement (including a sitting-to-standing paradigm) and that it is compatible with simultaneous electroencephalography (EEG - the clinical standard). Finally, we demonstrate portability by moving the system between two laboratories. Overall, our new system is shown to be a significant step forward for OPM-MEG technology and offers an attractive platform for next generation functional medical imaging.
    1:31a
    Maternal Alcohol Drinking Patterns Predict Offspring Neurobehavioral Outcomes
    SIGNIFICANCE: The timing, rate, and quantity of gestational alcohol consumption, collectively referred to here as Maternal Drinking Patterns (MDPs), are of known importance to fetal developmental outcomes. Though studies in rodents exist that have investigated the impact of gestational alcohol drinking characteristics, few have sought to determine the impact of MDPs on offspring behavioral outcomes. METHODS: We first used specialized equipment to record the precise amount and timing of binge alcohol consumption in pregnant mouse dams, and then characterized MDPs using Principle Component Analysis (PCA). We focused these analyses on the first fifteen minutes of every gestational drinking session when dams consumed the majority of each sessions alcohol (a phenomenon known as front-loading), as well as the entire 2 hour session across all days of gestation. We next tested offspring in open field and rotarod assays and evaluated these behavioral results in the context of MDPs. RESULTS: Male alcohol exposed mice exhibited longer latencies to fall on the rotarod compared to their controls, which we attribute to a delayed decrease in body weight-gain not observed in females. This effect was found to be associated with MDPs within the first fifteen minutes of drinking, but not other MDPs. Female alcohol exposed mice had significantly reduced total locomotor activity in the open field compared to controls, and this effect was also associated with MDPs but only of the entire drinking session. Surprisingly, total gestational alcohol consumption alone was not associated with any particular behavioral outcome. Furthermore, we replicated robust behavioral data demonstrating development of allodynia in alcohol exposed mice where it did not develop in controls. CONCLUSIONS: To our knowledge, this report represents the highest resolution assessment of alcohol drinking throughout gestation, and one of few to have identified relationships between specific alcohol MDPs and neurobehavioral outcomes in offspring. Specifically, based on characteristics of the PCA groups, we found evidence that the rate of alcohol front-loading leads to developmental delays in males, whereas an interaction of front-loading rate and duration, overall persistence, and total amount consumed lead to a female-only decrease in locomotor activity. Beyond these results, we provide a method for precise and accessible tracking of such data.
    1:31a
    PVN-mPFC OT projections modulates pup-directed pup care or attacking in virgin mandarin voles
    In many species, adult animals may exhibit caregiving or aggression towards conspecific offspring. The neural mechanisms underlying the infanticide and pup care remain poorly understood. Here, using monogamous virgin mandarin voles (Microtus mandarinus) that may exhibit pup care or infanticide, we found that more oxytocin (OT) neurons in the paraventricular nucleus (PVN) were activated during pup caring than infanticide. Optogenetic activation of OT neurons in the PVN facilitated pup-caring in male and female mandarin voles. In infanticide voles, optogenetic activation of PVN OT cells prolonged latency to approach and attack pups, whereas inhibition of these OT neurons facilitated approach and infanticide. In addition, OT release in the medial prefrontal cortex (mPFC) in pup-care voles increased upon approaching and retrieving pups, and decreased in infanticide voles upon attacking pups. Optogenetic activation of PVN OT neuron projections to the mPFC shortened the latency to approach and retrieve pups and facilitated the initiation of pup care, whereas inhibition of these projections had little effect. For pup-care females, neither activation nor inhibition of the terminals affected their behavior towards pups. In infanticide male and female voles, optogenetic activation of PVN-mPFC OT projection terminals prolonged the latency to approach and attack pups and suppressed the initiation of infanticide, whereas inhibition of these projections promoted approach and infanticide. Finally, we found that intraperitoneal injection of OT promoted pup care and inhibited infanticide behavior. It is suggested that the OT system, especially PVN OT neurons projecting to mPFC, modulates pup-directed behaviors and OT can be used to treat abnormal behavioral responses associated with some psychological diseases.
    1:31a
    Non-invasive MRI of Blood-Cerebrospinal Fluid-Barrier Function: a Functional Biomarker of Early Alzheimer's Disease Pathology
    INTRODUCTION Choroid plexus (CP) dysfunction is thought to contribute to toxic protein build-up in neurodegenerative disorders, including Alzheimer's disease (AD). However, the dynamics of this process remain unknown, mainly due to the paucity of in-vivo methods capable of assessing CP function. METHODS Here, we harness recent developments in Arterial Spin Labelling MRI to measure water delivery across the blood cerebrospinal fluid barrier (BCSFB) as a proxy for CP function, as well as cerebral blood flow (CBF), at different stages of AD progression in the widely used triple transgenic mouse model (3Tg), which recapitulates aspects of disease pathology. RESULTS Total BCSFB-mediated water delivery is significantly higher in 3Tg mice (>50%) from 8 weeks (preclinical stage), while tissue parameters such as CBF and T1 are not different between groups at all ages. DISCUSSION Our work shows changes in BCSFB function in the early stages of AD, providing a novel biomarker of pathology.
    1:31a
    Asymmetry in synaptic connectivity balances redundancy and reachability in the C. elegans connectome
    The brain is overall bilaterally symmetrical, but exhibits also considerable asymmetry. While symmetry may endow neural networks with robustness and resilience, asymmetry may enable parallel information processing and functional specialization. How is this functional tradeoff between symmetrical and asymmetrical brain architecture balanced? To address this, we focused on the C. elegans connectome, which comprises 99 classes of bilaterally symmetrical neuron pairs. We found symmetry in the number of synaptic partners between neuron class members, but pronounced asymmetry in the identity of these synapses. We developed graph theoretical metrics for evaluating Redundancy, the selective reinforcement of specific neural paths by multiple alternative synaptic connections, and Reachability, the extent of synaptic connectivity of each neuron class. We found Redundancy and Reachability to be stochastically tunable by the level of network asymmetry, driving the C. elegans connectome to favor Redundancy over Reachability. These results elucidate fundamental relations between lateralized neural connectivity and function.
    1:31a
    Dynamic properties in functional connectivity changes and striatal dopamine deficiency in Parkinson's disease
    Introduction: Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in separate PD cohorts, indexing dopamine-dependent changes in large-scale brain network dynamics and its implications in clinical features. Methods: We pooled data from two cohorts reflecting early PD. From the Parkinson's Progression Marker Initiative (PPMI) cohort, resting-state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) SPECT were available for 63 PD patients and 16 age- and sex-matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age- and sex-matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent 18F-DOPA-PET imaging. The striatal synthesis capacity of 18F-DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre-processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44s window) and a subsequent k-means clustering were conducted separately for each cohort to derive dFC states (reemerging intra- and interindividual connectivity patterns). From these states we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. Results: In both cohorts, dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state (X2(1, N=79) = 5.82, p= 0.016) and a lower number of transitions (U(N=79) = 337.5, z = -2.06 p= .039) than controls. Significantly, worse motor scores (UPDRS-III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state (UPDRS-III: {tau}b(N=63) = -.281; p =.003, DaT putamen: {tau}b(N=63)=.213, p= .023, DaT caudate: {tau}b(N=63)=.209, p= .025) and a low total number of transitions (UPDRS-III: {tau}b(N=63)= -.308; p = .001, DaT putamen: {tau}b(N=63)=.350, p<.001, DaT caudate: {tau}b(N=63)=.251, p=.007). Additionally, worse motor performance was associated with a low number of bi-directional transitions between the GI and the lesser connected (LC) state ({tau}b(N=63)= -.237; p =.019). These results could not be reproduced in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity or clinical measure were observed. Conclusion: In early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large-scale network dynamics seem to depend on striatal dopamine availability. Notably, we obtained these results in only one cohort, but not in a replication sample.
    4:44a
    TRPC6 is a mechanosensitive channel essential for ultrasound neuromodulation in mammalian brain
    Ultrasound neuromodulation has become an innovative technology that enables non-invasive intervention in mammalian brain circuits with high spatiotemporal precision. Despite the expanding utility of ultrasound neuromodulation in the neuroscience research field and clinical applications, the molecular and cellular mechanisms by which ultrasound impacts neural activity in the brain are still largely unknown. Here, we report that transient receptor potential canonical 6 (TRPC6), a mechanosensitive non-selective cation channel, is essential for ultrasound neuromodulation of mammalian neurons in vitro and in vivo. We first demonstrated that ultrasound irradiation elicited rapid and robust Ca2+ transients mediated via extracellular Ca2+ influx in cultured mouse cortical and hippocampal neurons. Ultrasound-induced neuronal responses were massively diminished by blocking either the generation of action potential or synaptic transmission. Importantly, both pharmacological inhibition and genetic deficiency of TRPC6 almost completely abolished neuronal responses to ultrasound. Furthermore, we found that intracerebroventricular administration of a TRPC6 blocker significantly attenuated the population of neuronal firings in the cerebral cortex evoked by transcranial ultrasound irradiation in mice. Our findings indicate that TRPC6 is an indispensable molecule of ultrasound neuromodulation in the intact mammalian brains, providing fundamental understanding of biophysical molecular mechanisms of ultrasound neuromodulation as well as insight into its future feasibility in neuroscience and translational researches in humans.
    7:02a
    High Frequency Terahertz Stimulation Alleviates Neuropathic Pain by Inhibiting the Pyramidal Neuron Activity in the Anterior Cingulate Cortex of mice
    Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system and is characterized by abnormal hypersensitivity to stimuli and nociceptive responses to non-noxious stimuli, affecting approximately 7-10% of the general population. However, current first-line drugs like non-steroidal anti-inflammatory agents and opioids have limitations, including dose-limiting side effects, dependence, and tolerability issues. Therefore, developing new interventions for the management of NP is urgent. In this study, we discovered that the high-frequency terahertz stimulation (HFTS) at approximate 36 THz effectively alleviates NP symptoms in mice with spared nerve injury. In vivo and in vitro results demonstrate that HFTS reduces the excitability of pyramidal neurons in the anterior cingulate cortex through enhancing the voltage-gated K+ (Kv) conductance. Computational simulation suggests that the frequency resonates with the carbonyl group in the filter region of Kv1.2 channels, facilitating the translocation of potassium ions. This research presents a novel optical intervention strategy with terahertz waves for the treatment of NP and holds promising application in other nervous system diseases.
    7:02a
    A method for estimating dynamic functional network connectivity gradients (dFNG) from ICA captures smooth inter-network modulation.
    Dynamic functional network connectivity (dFNC) analysis is a widely used approach for studying brain function and offering insight into how brain networks evolve over time. Typically, dFNC studies utilized fixed spatial maps and evaluate transient changes in coupling among time courses estimated from independent component analysis (ICA). This manuscript presents a complementary approach that relaxes this assumption by spatially reordering the components dynamically at each timepoint to optimize for a smooth gradient in the FNC (i.e., a smooth gradient among ICA connectivity values). Several methods are presented to summarize dynamic FNC gradients (dFNGs) over time, starting with static FNC gradients (sFNGs), then exploring the reordering properties as well as the dynamics of the gradients themselves. We then apply this approach to a dataset of schizophrenia (SZ) patients and healthy controls (HC). Functional dysconnectivity between different brain regions has been reported in schizophrenia, yet the neural mechanisms behind it remain elusive. Using resting state fMRI and ICA on a dataset consisting of 151 schizophrenia patients and 160 age and gender-matched healthy controls, we extracted 53 intrinsic connectivity networks (ICNs) for each subject using a fully automated spatially constrained ICA approach. We develop several summaries of our functional network connectivity gradient analysis, both in a static sense, computed as the Pearson correlation coefficient between full time series, and a dynamic sense, computed using a sliding window approach followed by reordering based on the computed gradient, and evaluate group differences. Static connectivity analysis revealed significantly stronger connectivity between subcortical (SC), auditory (AUD) and visual (VIS) networks in patients, as well as hypoconnectivity in sensorimotor (SM) network relative to controls. sFNG analysis highlighted distinctive clustering patterns in patients and HCs along cognitive control (CC)/ default mode network (DMN), SC/ AUD/ SM/ cerebellar (CB), and VIS gradients. Furthermore, we observed significant differences in the sFNGs between groups in SC and CB domains. dFNG analysis suggested that SZ patients spend significantly more time in a SC/ CB state based on the first gradient, while HCs favor the DMN state. For the second gradient, however, patients exhibited significantly higher activity in CB/ VIS domains, contrasting with HCs DMN engagement. The gradient synchrony analysis conveyed more shifts between SM/ SC networks and transmodal CC/ DMN networks in patients. In addition, the dFNG coupling revealed distinct connectivity patterns between SC, SM and CB centroids in SZ patients compared to HCs. To recap, our results advance our understanding of brain network modulation by examining smooth connectivity trajectories. This provides a more complete spatiotemporal summary of the data, contributing to the growing body of current literature regarding the functional dysconnectivity in schizophrenia patients. By employing dFNG, we highlight a new perspective to capture large scale fluctuations across the brain while maintaining the convenience of brain networks and low dimensional summary measures.
    10:32a
    Monkeys have rhythnm
    Synchronizing movements to music is one of the hallmarks of human culture whose evolutionary and neurobiological origins remain unknown. The ability to synchronize movements requires 1) detecting a steady rhythmic pulse, or beat, out of a stream of complex sounds, 2) projecting this rhythmic pattern forward in time to predict future input, and 3) timing motor commands in anticipation of predicted future beats. Here, we demonstrate that the macaque is capable of synchronizing taps to a subjective beat in real music, and even spontaneously chooses to do so over alternative strategies. This contradicts the influential 'vocal learning hypothesis' that musical beat synchronization is only possible in species with complex vocalizations such as humans and some songbirds. We propose an alternative view of musical beat perception and synchronization ability as a continuum onto which a wider range of species can be mapped depending on their ability to perform and coordinate the general abilities listed above through association with reward.
    10:32a
    Dorsal hippocampus represents locations to avoid as well as locations to approach during approach-avoidance conflict
    Worrying about perceived threats is a hallmark of multiple psychological disorders including anxiety. This concern about future events is particularly important when an individual is faced with an approach-avoidance conflict. Potential goals to approach are known to be represented in the dorsal hippocampus during theta sweeps. Similarly, important non-local information is represented during hippocampal high synchrony events (HSEs), which are correlated with sharp-wave ripples (SWRs). It is likely that potential future threats may be similarly represented. We examined how threats and rewards were represented within the hippocampus during approach-avoidance conflicts in rats faced with a predator-like robot guarding a food reward. We found representations of the pseudo-predator during HSEs when hesitating in the nest, and during theta prior to retreating as the rats approached the pseudo-predator. After the first attack, we observed new place fields appearing at the location of the robot (not the location the rat was when attacked). The anxiolytic diazepam reduced anxiety-like behavior and altered hippocampal local field potentials, including reducing SWRs, suggesting that one potential mechanism of diazepam's actions may be through altered representations of imagined threat. These results suggest that hippocampal representation of potential threats could be an important mechanism that underlies worry and a potential target for anxiolytics.
    10:32a
    A shifting role of thalamocortical connectivity in the emergence of large-scale functional brain organization across early lifespan development
    While cortical patterning has been a perennial research topic in neuroscience, the mechanism for its consequence, namely functional specialization at the macro scale, remains an open question in the human brain. Here, we focused on age-dependent changes of resting-state thalamocortical connectivity to investigate its role in the emergence of large-scale functional networks across infancy, childhood and young adulthood. We found that the thalamocortical connectivity during infancy reflects an early differentiation of sensorimotor networks and genetically-influenced axonal projection. This initial role of the thalamus, however, seems to change during childhood, by establishing connectivity with the salience network and decoupling externally- and internally-oriented functional processes. Developmental simulation and perturbation analyses corroborated these findings, demonstrating the highest contribution of thalamic connectivity, especially in the later age of youth, in the formation of key characteristics of the mature brain, such as functional gradient and cortical hierarchy. Our study highlights a developmentally shifting role of the thalamus in orchestrating complex brain organization and its potential implications for developmental conditions characterized by compromised internal and external processing.
    10:32a
    Layer 5 Martinotti cell activation reduces pyramidal cell population plasticity and improves fine motor function
    During motor activity and motor learning, pyramidal cells in the motor cortex receive inputs from local interneurons as well as deeper structures. These signals funnel into pyramidal cells in the primary motor cortex that in turn feed commands to spinal circuits for execution. Here we show that layer 5 Chrna2 Martinotti cells receive direct input from thalamic nuclei, and that their genetic ablation results in disturbed fine motor functions. Activation of these layer 5 Martinotti cells during training reduces pyramidal cell plasticity, e.g. tuning, temporal patterning and assembly configuration. Moreover, in mice that had already learned a reach-and-grasp (prehension) task, Martinotti cell activation resulted in improved prehension. This work indicates that activation of layer 5 Martiotti cells reduces pyramidal cell assembly plasticity during learning, facilitating preservation of already acquired motor skills.
    10:32a
    Estradiol and Flutamide Effects on the Song System of Developing Male Zebra Finches
    Estradiol (E2) masculinizes the developing song system of female zebra finches (Taeniopygia castanotis) if it is administered in early life, but the effects of E2 on the developing song system in males have not been thoroughly explored. Also, reports of early antiandrogen administration in developing male zebra finches differ in their findings. Therefore, this study was conducted to further explore the effects of administering E2 alone, flutamide (Flut) alone, or the two in combination during early development. Brains and testes were examined after day 100. The results showed definite demasculinizing effects of early E2 on the song nucleus HVC (proper name) its volume and neuron number were markedly reduced. Nonetheless, early E2 hypermasculinized HVC neuronal size. Flut slightly hypermasculinized RA volume (Robust nucleus of the Arcopallium), which replicates a previous study, but the absence of any additional effects is at odds with other studies. Arguments are put forward suggesting that early E2 action on HVC development could be a consequence of differential steroid action on the male versus female genotype and/or a disruption of the temporal sequence of gene regulation in developing males. Early E2 resulted in markedly reducing testes size, which is likely to be a consequence of hijacking endogenous endocrine feedback mechanisms. The reduction in testes size suggests low steroid secretion, which also could contribute to the demasculinization of HVC.
    10:32a
    MULTIMODAL GRADIENTS UNIFY LOCAL AND GLOBAL CORTICAL ORGANIZATION
    Specialization of brain areas and subregions, as well as their integration into large-scale networks are key principles in neuroscience. Consolidating both local and global cortical organization, however, remains challenging. Our study developed a new approach to map global, cortex-wise similarities of microstructure, structural connectivity, and functional interactions, and integrate these patterns with maps of cortical arealization. Our analysis combined repeated high-field in-vivo 7 tesla (T) Magnetic Resonance Imaging (MRI) data collected in 10 healthy adults with a recently introduced probabilistic post-mortem atlas of cortical cytoarchitecture. We obtained multimodal eigenvectors describing cortex-wide gradients at the level of microstructural covariance, structural connectivity, and intrinsic functional interactions, and then assessed inter- and intra-area differences in cortex-wide embedding based on these multimodal eigenvectors. Inter-area similarities followed a canonical sensory-fugal gradient, with primary sensorimotor cortex being the most distinctive from all other areas, while paralimbic regions were least distinctive. This pattern largely corresponded to functional connectivity variations across different tasks collected in the same participants, suggesting that the degree of global cortical integration mirrors the functional diversity of brain areas across contexts. When studying heterogeneity within areas, we did not observe a similar relationship, despite overall higher heterogeneity in association cortices relative to paralimbic and idiotypic cortices. Findings could be replicated in a different dataset. Our findings highlight a close coupling between cortical arealization and global cortical motifs in shaping specialized versus integrative human brain function.
    11:46a
    The P600 during sentence reading predicts behavioral and neural markers of recognition memory
    The P600 ERP component is elicited by a wide range of anomalies and ambiguities during sentence comprehension and remains important for neurocognitive models of language processing. It has been proposed that the P600 is a more domain-general component, signaling phasic norepinephrine release from the locus coeruleus in response to salient stimuli that require attention and behavioral adaptation. Since such norepinephrine release promotes explicit memory formation, we here investigated whether the P600 during sentence reading (encoding) is thus predictive of such explicit memory formation using a subsequent old/new word recognition task. Indeed, the P600 amplitude during our encoding task was related to behavioral recognition effects in the memory task on a trial-by-trial basis, though only for one type of violation. Recognition performance was better for semantically, but not syntactically violated words that had previously elicited a larger P600. However, the P600 to both types of violations during encoding was positively related to a more subtle, neural marker of recognition, namely the amplitude of the old/new recollection ERP component. In sum, we find that the P600 predicts later recognition memory both on the behavioral and neural level. Such explicit memory effects further link the late positivity to norepinephrine activity, suggesting a more domain-general nature of the component. The connection between the P600 and later recognition indicates that the neurocognitive processes that deal with salient and anomalous aspects in the linguistic input in the moment will also be involved in keeping this event available for later recognition.
    3:16p
    The acute effects of cocoa flavanols on cognitive control and response inhibition: A randomised crossover trial
    In this pre-registered study, we investigated the effects of acute cocoa flavanol (CF) consumption on cognitive control and response inhibition processes, at two different dosage levels. This study was randomised, placebo-controlled, gender-balanced, double-blind, and utilised a crossover design. Participants consumed three different drinks across three separate sessions: A placebo drink with alkalised cocoa powder, a low dosage (415 mg), and a medium dosage (623 mg) of cocoa flavanols from flavanol-rich cocoa powder. Following the administration of these treatment conditions, participants were tested in the Flanker, Simon, and Go/No-go tasks in a counterbalanced order in each session. We analysed accuracy and response times from incongruent and congruent trials of the Simon and Flanker tasks, and commission errors, omission errors, and response times for the Go/No-go task. In addition to these main measurements, we considered interference and sequence effects, accounting for the influence of previous trials in Simon and Flanker tasks. The acute effects of CF on cognitive control and response inhibition were examined using (Generalised) Linear Mixed Model analysis, which included random intercepts, fixed effects, and random slopes. Analysis results revealed that neither dose of cocoa flavanols consumption acutely improved accuracies, interferences, errors, or response times in these three tasks. Furthermore, neither the gender of participants nor BMI scores predicted their cognitive control and response inhibition functions in addition to the treatment conditions. Our findings suggest that acute consumption of cocoa flavanols does not significantly enhance cognitive control or response inhibition in healthy young adults.

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