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Smoking is a severe addictive health risk behavior and notorious for the high likelihood of relapse after attempted cessation. Such an addictive pattern in smoking has been associated with neurobiological changes in the brain. However, little is known whether the neural changes associated with chronic smoking persist after a long period of successful abstinence. To address this question, we examined resting state EEG (rsEEG) in chronic smokers who have been smoking for 20 years or more, past-smokers who have been successfully abstaining for 20 years or more, and never-smokers. Both current-smokers and past-smokers showed significantly decreased relative theta power than never-smokers, showcasing persistent effect of smoking on the brain. Other rsEEG features in alpha frequency band demonstrated distinctive patterns associated with active smoking, such that compared to never-smokers, only current-smokers, but not past-smokers, showed significantly higher relative power, EEG reactivity-power changes between eyes-closed and eyes-open conditions-, and coherence between channels. Furthermore, individual variabilities across these rsEEG biomarkers were accounted for by individuals' self-reported smoking history and nicotine dependence in current- and past- smokers. These data suggest the persistent effect of smoking on the brain even after sustained remission for 20 years., (© 2023. The Author(s).)

Spontaneous neural activity has been widely adopted to construct functional connectivity (FC) amongst distant brain regions. Although informative, the functional role and signaling mechanism of the resting state FC are not intuitive as those in stimulus/task-evoked activity. In order to bridge the gap, we investigated anesthetic modulation of both resting-state and sensory-evoked activities. We used two well-studied GABAergic anesthetics of varying dose (isoflurane: 0.5-2.0% and α-chloralose: 30 and 60 mg/kg∙h) and recorded changes in electrophysiology using a pair of laminar electrode arrays that encompass the entire depth of the bilateral somatosensory cortices (S1fl) in rats. Specifically, the study focused to describe how varying anesthesia conditions affect the resting state activities and resultant FC between bilateral hemispheres in comparison to those obtained by evoked responses. As results, isoflurane decreased the amplitude of evoked responses in a dose-dependent manner mostly due to the habituation of repetitive responses. However, α-chloralose rather intensified the amplitude without exhibiting habituation. No such diverging trend was observed for the spontaneous activity, in which both anesthetics increased the signal power. For α-chloralose, overall FC was similar to that obtained with the lowest dose of isoflurane at 0.5% while higher doses of isoflurane displayed increased FC. Interestingly, only α-chloralose elicited relatively much greater increases in the ipsi-stimulus evoked response (i.e., in S1fl ipsilateral to the stimulated forelimb) than those associated with the contra-stimulus response, suggesting enhanced neuronal excitability. Taken together, the findings demonstrate modulation of the FC profiles by anesthesia is highly non-linear, possibly with a distinct underlying mechanism that affects either resting state or evoked activities differently. Further, the current study warrants thorough investigation of the basal neuronal states prior to the interpretation of resting state FC and evoked activities for accurate understanding of neural signal processing and circuitry., (© 2022. The Author(s).)

Tissue clearing has gained attention as a pioneering research tool for imaging of large tissue samples. This technique improves light transmission by reducing light scattering within tissues, either by removing lipids or by replacing water with a high refractive index solution. Although various clearing techniques have been developed, quantitative assessments on clearing efficacy depending on tissue properties are rare. In this study, we developed the quantitative mapping of regional clearing efficacy using mean free path in optical coherence tomography (OCT) and proton density in magnetic resonance imaging (MRI), and demonstrated its feasibility in the brain sample with four representative clearing techniques (benzyl alcohol and benzyl benzoate [BABB], Clear T , Scale, and passive CLARITY technique [PACT]). BABB (solvent-based clearing), involving both refractive index matching and lipid removal, exhibited best optical clearing performance with the highest proton density reduction both in gray and white matter. Lipid-removing techniques such as Scale (aqueous hyperhydration) and PACT (hydrogel embedding) showed higher clearing efficiency in white matter than gray matter in accordance with larger proton density increase in white matter. For Clear T (aqueous-based simple immersion), we observed lowest clearing efficiency in the white matter as well as poor lipid removal reflected in low proton density reduction. Our results showed the feasibility of the regional mapping of clearing efficacy and correlating optical transparency and proton density changes using OCT and MRI from existing tissue clearing techniques. This novel quantitative mapping of clearing efficacy depending on tissue types and clearing methods may be helpful in the development of optimized clearing methods for different biological samples.

Suicide attempters have been found to be impaired in decision-making; however, their specific biases in evaluating uncertain outcomes remain unclear. Here we tested the hypothesis that suicidal behavior is associated with heightened aversion to risk and loss, which might produce negative predictions about uncertain future events. Forty-five depressed patients with a suicide attempt history, 47 nonsuicidal depressed patients, and 75 healthy controls participated in monetary decision-making tasks assessing risk and loss aversion. Suicide attempters compared with the other groups exhibited greater aversion to both risk and loss during gambles involving potential loss. Risk and loss aversion correlated with each other in the depressed patients, suggesting that a common pathophysiological mechanism underlies these biases. In addition, emotion regulation via suppression, a detrimental emotional control strategy, was positively correlated with loss aversion in the depressed patients, also implicating impairment in regulatory processes. A preliminary fMRI study also found disrupted neural responses to potential gains and losses in the subgenual anterior cingulate cortex, insula cortex, and left amygdala, brain regions involved in valuation, emotion reactivity, and emotion regulation. The findings thus implicate heightened negative valuation in decision-making under risk, and impaired emotion regulation in depressed patients with a history of suicide attempts.

We focus on exploratory decisions across disorders of compulsivity, a potential dimensional construct for the classification of mental disorders. Behaviors associated with the pathological use of alcohol or food, in alcohol use disorders (AUD) or binge-eating disorder (BED), suggest a disturbance in explore-exploit decision-making, whereby strategic exploratory decisions in an attempt to improve long-term outcomes may diminish in favor of more repetitive or exploitatory choices. We compare exploration vs exploitation across disorders of natural (obesity with and without BED) and drug rewards (AUD). We separately acquired resting state functional MRI data using a novel multi-echo planar imaging sequence and independent components analysis from healthy individuals to assess the neural correlates underlying exploration. Participants with AUD showed reduced exploratory behavior across gain and loss environments, leading to lower-yielding exploitatory choices. Obese subjects with and without BED did not differ from healthy volunteers but when compared with each other or to AUD subjects, BED had enhanced exploratory behaviors particularly in the loss domain. All subject groups had decreased exploration or greater uncertainty avoidance to losses compared with rewards. More exploratory decisions in the context of reward were associated with frontal polar and ventral striatal connectivity. For losses, exploration was associated with frontal polar and precuneus connectivity. We further implicate the relevance and dimensionality of constructs of compulsivity across disorders of both natural and drug rewards.

The compulsive behaviour underlying obsessive-compulsive disorder (OCD) may be related to abnormalities in decision-making. The inability to commit to ultimate decisions, for example, patients unable to decide whether their hands are sufficiently clean, may reflect failures in accumulating sufficient evidence before a decision. Here we investigate the process of evidence accumulation in OCD in perceptual discrimination, hypothesizing enhanced evidence accumulation relative to healthy volunteers. Twenty-eight OCD patients and thirty-five controls were tested with a low-level visual perceptual task (random-dot-motion task, RDMT) and two response conflict control tasks. Regression analysis across different motion coherence levels and Hierarchical Drift Diffusion Modelling (HDDM) were used to characterize response strategies between groups in the RDMT. Patients required more evidence under high uncertainty perceptual contexts, as indexed by longer response time and higher decision boundaries. HDDM, which defines a decision when accumulated noisy evidence reaches a decision boundary, further showed slower drift rate towards the decision boundary reflecting poorer quality of evidence entering the decision process in patients under low uncertainty. With monetary incentives emphasizing speed and penalty for slower responses, patients decreased the decision thresholds relative to controls, accumulating less evidence in low uncertainty. These findings were unrelated to visual perceptual deficits and response conflict. This study provides evidence for impaired decision-formation processes in OCD, with a differential influence of high and low uncertainty contexts on evidence accumulation (decision threshold) and on the quality of evidence gathered (drift rates). It further emphasizes that OCD patients are sensitive to monetary incentives heightening speed in the speed-accuracy tradeoff, improving evidence accumulation.