Nathan Thomas Matthew Huneke

Blood–brain barrier (BBB) dysfunction is implicated as a key link between neuroinflammation and neurodegeneration in Alzheimer’s disease (AD). Peripheral inflammation may exacerbate cognitive decline by promoting BBB breakdown and impairing clearance of amyloid and tau, yet in vivo evidence for this hypothesis remains limited. We conducted a pilot cohort study to assess the feasibility of utilising dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to quantify BBB permeability in AD, and to explore associations with cognitive decline, peripheral inflammation, and neurodegeneration. Fourteen participants with clinically diagnosed AD and 16 matched controls underwent baseline clinical, blood, urine, and DCE-MRI assessments. Thirteen AD participants were clinically reassessed after 12 months. BBB permeability was quantified using Patlak modelling in whole brain, grey and white matter, and selected regions of interest. Serum cytokines, phosphorylated tau-181 (pTau-181), neurofilament light (NfL), and urinary neopterin were analysed. BBB permeability did not differ significantly between AD and controls across global or regional measures at baseline. However, higher baseline permeability in the left entorhinal cortex was significantly associated with greater cognitive decline over 12 months. AD participants exhibited elevated serum interferon-γ relative to controls, and higher baseline interleukin-6 was associated with faster cognitive decline. This pilot study supports feasibility of regional DCE-MRI measurement in people with AD. Larger biomarker-confirmed cohorts are warranted to evaluate prognostic utility and to clarify the interaction between peripheral inflammation, BBB dysfunction and clinical progression in AD.

Summary: Anxiety disorders are distressing and impairing and may be becoming more prevalent. There remains much uncertainty about key factors in the development and maintenance of anxiety disorders, which may underpin some of the limitations of existing psychological, pharmacological and other treatments.

Background: We need to identify novel, tractable therapeutic targets for anxiety disorders. Converging evidence suggests the endogenous opioid system plays a role in modulating affective processing, but its contribution to regulation of threat processing in humans remains unclear. Aims: We investigated the neural correlates of non-specific opioid antagonism on explicit and implicit regulation of threatening stimuli in healthy volunteers, using functional magnetic resonance imaging (fMRI). Method: In a randomised, double-blind, placebo-controlled, crossover design, 38 healthy participants received the opioid antagonist naltrexone (50 mg) or placebo before completing two tasks during fMRI: (a) a cognitive emotional reappraisal task probing explicit regulation and (b) a face-viewing task probing implicit processing. Results: Contrary to our hypothesis, we found naltrexone reduced distress ratings during the reappraisal task ( p = 0.044) without impairing regulation success. Explicit regulation in the reappraisal task engaged lateral prefrontal regions similarly across drug conditions. However, naltrexone attenuated ventromedial prefrontal cortex, thalamus and caudate activation when viewing negative images. Naltrexone additionally altered ventromedial prefrontal cortex activity and in task-positive regions including right premotor area and frontal pole compared with placebo when viewing emotional faces. In particular, naltrexone increased left middle frontal gyrus activity when viewing fearful faces. Conclusions: Our results support a role for opioid signalling in automatic emotional regulation, but not in explicit regulation. Furthermore, naltrexone appeared to diminish activity in task-positive regions in response to emotional faces. These findings are consistent with a model where endogenous opioids ‘fine-tune’ affective responses to both negative and positive stimuli. Future research should explore dose–response effects, kappa-opioid contributions and whether similar results are seen in clinical populations.

This study investigates how virtual communication differs from in-person interaction across physiological and behavioral domains, with the goal of informing future interface design. Using a naturalistic setup, we recorded multimodal biosignals, including eye tracking, head and hand movement, heart rate, respiratory rate, and EEG during both in-person and video-based dialogues. Our results show that virtual communication significantly reduces movement and gaze dynamics, particularly in horizontal eye movements and lateral head motion, reflecting both sender- and receiver-side constraints. These physical limitations likely stem from the need to remain within the camera frame and the restricted access to nonverbal cues. Pupil dilation was significantly greater during in-person conversations, consistent with increased arousal during natural communication. Heart rate and EEG trends similarly suggested heightened engagement in face-to-face settings, though interpretation of EEG was limited by movement artifacts. Together, the findings highlight how virtual platforms alter embodied interaction, underscoring the need to address both mobility and visual access in future communication technologies to better support co-presence.

This study investigates how virtual communication differs from in-person interaction across physiological and behavioral domains, with the goal of informing future interface design. Using a naturalistic setup, we recorded multimodal biosignals, including eye tracking, head and hand movement, heart rate, respiratory rate, and EEG during both in-person and video-based dialogues. Our results show that virtual communication significantly reduces movement and gaze dynamics, particularly in horizontal eye movements and lateral head motion, reflecting both sender- and receiver-side constraints. These physical limitations likely stem from the need to remain within the camera frame and the restricted access to nonverbal cues. Pupil dilation was significantly greater during in-person conversations, consistent with increased arousal during natural communication. Heart rate and EEG trends similarly suggested heightened engagement in face-to-face settings, though interpretation of EEG was limited by movement artifacts. Together, the findings highlight how virtual platforms alter embodied interaction, underscoring the need to address both mobility and visual access in future communication technologies to better support co-presence.

Background: Contemporary society faces significant challenges that can lead to stress-induced tunnel vision. Positive affect can counteract these effects by expanding humans’ attentional scope, potentially promoting resilience and creativity. This preregistered triple-blind study investigated the role of endogenous opioids in mediating attentional broadening following reward receipt. Methods: Using a placebo-controlled crossover design, 40 volunteers underwent two sessions separated by at least 1 week, receiving either 50 mg of naltrexone or a placebo. Participants completed a Navon letters task designed to contrast the effects of reward receipt versus reward anticipation on attentional scope. Results: As predicted, our results show that the attentional broadening observed after reward receipt under placebo was eliminated when opioid receptors were blocked. Naltrexone did not result in blunted reward anticipation effects on task performance or attentional narrowing. Conclusions: This study highlights the role of endogenous opioids in attentional breadth and their potential for cognitive flexibility and resilience through natural positive experiences, with potential implications for mental health and stress management.

Social Anxiety Disorder (SAD) is a prevalent and debilitating condition characterized by heightened anxiety and avoidance behaviors in social situations. Despite the availability of treatment options, remission rates for SAD remain low, highlighting the need for more effective therapies. This pilot study investigates whether anticipatory anxiety before a social interaction can be detected through a combination of multiple biosignals, with the aim of identifying potential biomarkers for SAD. Using a modified version of the Internet-based Stress Test for Social Anxiety Disorder (ITSSAD), we measured physiological responses, including heart rate, respiratory rate, electrodermal activity, head movements, and EEG power across various frequencies. We found that anticipatory anxiety was associated with increased heart rate, respiratory rate, tonic EDA, and variance in head roll, alongside elevated theta, beta, and gamma power in EEG. Our results suggest that a combination of these biosignals may provide valuable insight into the psychophysiological profile of social anxiety, which could be useful for both mechanistic research and clinical applications. Future research should explore the role of these signals in clinical populations and during acute threat conditions to refine diagnostic and prognostic tools for SAD.