Biology subjects

Weber, B.

Publications and source records attributed to Weber, B..

6 recordsLinked to original sources

bioRxiv2026

PURELIGHT: a quantitative photon-counting framework unifying intensity and lifetime imaging at video rate across detector technologies

Quantitative fluorescence microscopy requires photon-efficiency, speed and accurate intensity and lifetime measurements. Time-correlated single-photon counting (TCSPC) simultaneously captures intensity and lifetime, but photon pile-up distorts both signals at high count rates, preventing fast acquisitions. Existing corrections discard photons, distort intensity, or require specialized detectors. Here we introduce PURELIGHT, an integrated hardware and software framework that simultaneously recovers undistorted intensities and lifetimes at count rates far beyond conventional pile-up limits. PURELIGHT works with hybrid photodetectors, silicon photomultipliers and photomultiplier tubes while retaining over three times more photons than alternative approaches. Using two-photon imaging, we showcase PURELIGHT's superior accuracy and spatial contrast, demonstrating video-rate subcellular lifetime imaging in awake mice, a unique lifetime-calibrated ratiometric modality and crosstalk-free temporal multiplexing. By removing the limits that have confined TCSPC to low-signal applications, PURELIGHT promotes the adoption of quantitative, photon-efficient microscopy across the life sciences.

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

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↗

bioRxiv2017

Forgot what you like? Evidence for hippocampal dependence of value-based decisions

Consistent decisions are intuitively desirable and theoretically important for utility maximization. Neuroeconomics has established the neurobiological substrate of value representation, but brain regions that provide input to the value-processing network is less explored. The constructed-preference tradition within behavioral decision research gives a critical role to cognitive processes that rely on associations, suggesting a role for the hippocampus in making decisions and to do so consistently. We compared the performance of 31 patients with mediotemporal lobe (MTL) epilepsy and hippocampal lesions, 30 patients with extratemporal lobe epilepsy, and 30 healthy controls on two tasks: binary choices between candy bars based on their preferences and a number-comparison control task where the larger number is chosen. MTL patients make more inconsistent choices than the other two groups for the value-based choice but not the number-comparison task. These inconsistencies increase with the volume of compromised hippocampal tissue. These results suggest a critical involvement of the MTL in preference construction and value-based choices.\n\nSignificanceOur days are full of choices that reflect our preferences. Economics lays out models of how to optimally make these decisions. Neuroeconomics has identified a cortical value-processing network whose activity correlates with constructs related to valuation and choice in economic models. However open questions remain: How are these value signals formed, and what regions might be necessary for retrieving and computing these value signals? Inspired by cognitive models calling on associative processes in value-based decisions, this paper uses unique neuropsychological data to establish the critical role of the medial temporal lobe in making consistent choices and further informs our understanding of the value-processing network.

animal behavior and cognition↗

bioRxiv2017

How context alters value: Price information recruits the brain’s valuation and affective regulation system for shaping experienced taste pleasantness

Informational cues such as the price of a wine can trigger expectations about its taste quality and thereby modulate the sensory experience on a reported and neural level. Yet it is unclear how the brain translates such expectations into sensory pleasantness. We used multilevel mediation analysis of neural and behavioral data obtained in participants who tasted identical wines cued with different prices. We found that the brain's valuation system (BVS) in concert with the anterior prefrontal cortex explained the effect of price cues on taste pleasantness ratings. The sensitivity of the BVS to rewards outside the taste domain moderated the strength of these effects. Moreover, brain mediators of price cue effects overlapped with brain regions previously found to be involved in placebo analgesia. These findings provide novel evidence for the fundamental role that neural pathways linked to motivation and affective regulation play for the effect of informational cues on sensory experiences.

neuroscience↗