Anterior Prefrontal Cortex Research Articles

A Multimodal Magnetic Resonance Imaging Study on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Feasibility and Clinical Correlation.

Background/Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neurological disorder characterized by post-exertional malaise. Despite its clinical relevance, the disease mechanisms of ME/CFS are not fully understood. The previous studies targeting brain function or metabolites have been inconclusive in understanding ME/CFS complexity. We combined single-voxel magnetic resonance spectroscopy (SV-MRS) and functional magnetic resonance imaging (fMRI). Our objectives were to examine the feasibility of the multimodal MRI protocol, identify possible differences between ME/CFS and healthy controls (HCs), and relate MRI findings with clinical symptoms. Methods: We enrolled 18 female ME/CFS participants (mean age: 39.7 ± 12.0 years) and five HCs (mean age: 45.6 ± 14.5 years). SV-MRS spectra were acquired from three voxels of interest: the anterior cingulate gyrus (ACC), brainstem (BS), and left dorsolateral prefrontal cortex (L-DLPFC). Whole-brain fMRI used n-back task testing working memory and executive function. The feasibility was assessed as protocol completion rate and time. Group differences in brain metabolites and fMRI activation between ME/CFS and HCs were compared and correlated with behavioral and symptom severity measurements. Results: The completion rate was 100% regardless of participant group without causing immediate fatigue. ME/CFS appeared to show a higher N-Acetylaspartate in L-DLPFC compared to HCs (OR = 8.49, p = 0.040), correlating with poorer fatigue, pain, and sleep quality scores (p's = 0.001-0.015). An increase in brain activation involving the frontal lobe and the brainstem was observed in ME/CFS compared to HCs (Z > 3.4, p's < 0.010). Conclusions: The study demonstrates the feasibility of combining MRS and fMRI to capture neurochemical and neurophysiological features of ME/CFS in female participants. Further research with larger cohorts of more representative sampling and follow-ups is needed to validate these apparent differences between ME/CFS and HCs.

Different neural correlates of deception: Crafting high and low creative scams

Deception is a complex social behavior that manifests in various forms, including scams. To successfully deceive victims, liars have to continually devise novel scams. This ability to create novel scams represents one kind of malevolent creativity, referred to as lying. This study aimed to explore different neural substrates involved in the generation of high and low creative scams. A total of 40 participants were required to design several creative scams, and their cortical activity was recorded by functional near-infrared spectroscopy. The results revealed that the right frontopolar cortex (FPC) was significantly active in scam generation. This region associated with theory of mind may be a key region for creating novel and complex scams. Moreover, creativity-related regions were positively involved in creative scams, while morality-related areas showed negative involvement. This suggests that individuals might attempt to use malevolent creativity while simultaneously minimizing the influence of moral considerations. The right FPC exhibited increased coupling with the right precentral gyrus during the design of high-harmfulness scams, suggesting a diminished control over immoral thoughts in the generation of harmful scams. Additionally, the perception of the victim’s emotions (related to right pre-motor cortex) might diminish the quality of highly original scams. Furthermore, an efficient and cohesive neural coupling state appears to be a key factor in generating high-creativity scams. These findings suggest that the right FPC was crucial in scam creation, highlighting a neural basis for balancing malevolent creativity against moral considerations in high-creativity deception.

Effects of Phasic Activation of Locus Ceruleus on Cortical Neural Activity and Auditory Discrimination Behavior.

Although the locus ceruleus (LC) is recognized as a crucial modulator for attention and perception by releasing norepinephrine into various cortical regions, the impact of LC-noradrenergic (LC-NE) modulation on auditory discrimination behavior remains elusive. In this study, we firstly recorded local field potential and single-unit activity in multiple cortical regions associated with auditory-motor processing, including the auditory cortex, posterior parietal cortex, secondary motor cortex, anterior cingulate cortex, prefrontal cortex, and orbitofrontal cortex (OFC), in response to optogenetic activation (40 Hz and 0.5 s) of the LC-NE neurons in awake mice (male). We found that phasic LC stimulation induced a persistent high gamma oscillation (50-80 Hz) in the OFC. Phasic activation of LC-NE neurons also resulted in a corresponding increase in norepinephrine levels in the OFC, accompanied by a pupillary dilation response. Furthermore, when mice were performing a go/no-go auditory discrimination task, we optogeneticaly activated the neural projections from LC to OFC and revealed a shortened latency in behavioral responses to sound stimuli and an increased false alarm rate. These impulsive behavioral responses may be associated with the gamma neural activity in the OFC. These findings have broadened our understanding of the neural mechanisms involved in the role of LC in auditory-motor processing.

Abnormal dynamics of functional connectivity density and effective connectivity in overactive bladder.

The study aims to analyze alterations in dynamic functional connectivity density (dFCD) and effective connectivity (dEC) patterns using functional magnetic resonance imaging (fMRI), hypothesizing that overactive bladder (OAB) patients will exhibit distinct dFCD and dEC patterns, reflecting altered neural communication underlying the OAB. Forty-three female OAB patients and 40 female healthy controls (HC) underwent resting-state fMRI. Sliding window correlation was used to calculate the variability of the dFCD. The changes in dFCD-based dEC between the two groups were examined using Granger causal analysis. To describe the time-varying Granger causality, a sliding-window approach was utilized to divide time courses into a group of windows. We adopted a k-means clustering method to cluster all matrices into discrete connectivity states. Compared with HC, OAB females consistently had a dFCD (decreased) in the left anterior cingulate cortex (ACC) and left medial prefrontal cortex (mPFC) (p < 0.05, GRF corrected). In state 1, OAB patients had excitatory effective connections from bilateral ACC to left mPFC in comparison to HC. In state 2, there was an increase in dEC from the SMA to the mPFC. Participants with OAB showed significantly more inhibitory dorsolateral prefrontal cortex (dlPFC) connections between the left ACC and the right ACC in state 4, as well as an excitatory dEC connection between the right dlPFC and the left ACC in state 2 (p < 0.05, GRF corrected). OAB patients demonstrate significant alterations in dFCD and dEC patterns, which may be indicative of the neural mechanisms involved in OAB pathophysiology.

Brain activation patterns in patients with post-stroke cognitive impairment during working memory task: a functional near-infrared spectroscopy study.

To explore the activation patterns in the frontal cortex of patients with post-stroke cognitive impairment during the execution of working memory tasks. 15 patients with post-stroke cognitive impairment, 17 patients without cognitive impairment, and 15 healthy controls of similar age and sex were included. All participants under-went immediate recall task testing and near-infrared spectroscopy imaging to measure frontal cortex activation during the task. The healthy control group performed the best in the immediate recall task, followed by the post-stroke non-cognitive impairment group. The post-stroke cognitive impairment group had the poorest performance. The near-infrared spectroscopy results revealed that during the immediate recall task, the healthy control group primarily activated the left frontal lobe region. In contrast, post-stroke patients exhibited reduced activation in the left frontal lobe and increased activation in the right frontal cortex, particularly in the right frontopolar and orbitofrontal regions, with the post-stroke cognitive impairment group displaying the most pronounced changes. Patients with post-stroke cognitive impairment exhibit reduced activation in the left prefrontal cortex during the working memory tasks. They rely on compensatory activation in the right prefrontal cortex, particularly in the frontopolar and orbitofrontal cortex, to successfully complete the task.

Neural mechanisms of credit assignment for delayed outcomes during contingent learning.

Adaptive behavior in complex environments critically relies on the ability to appropriately link specific choices or actions to their outcomes. However, the neural mechanisms that support the ability to credit only those past choices believed to have caused the observed outcomes remain unclear. Here, we leverage multivariate pattern analyses of functional magnetic resonance imaging (fMRI) data and an adaptive learning task to shed light on the underlying neural mechanisms of such specific credit assignment. We find that the lateral orbitofrontal cortex (lOFC) and hippocampus (HC) code for the causal choice identity when credit needs to be assigned for choices that are separated from outcomes by a long delay, even when this delayed transition is punctuated by interim decisions. Further, we show when interim decisions must be made, learning is additionally supported by lateral frontopolar cortex (FPl). Our results indicate that FPl holds previous causal choices in a "pending" state until a relevant outcome is observed, and the fidelity of these representations predicts the fidelity of subsequent causal choice representations in lOFC and HC during credit assignment. Together, these results highlight the importance of the timely reinstatement of specific causes in lOFC and HC in learning choice-outcome relationships when delays and choices intervene, a critical component of real-world learning and decision making.

Are older adults less generous? Age differences in emotion-related social decision making

In social interaction, age-related differences in emotional processing may lead to varied social decision making between young and older adults. However, previous studies of social decision making have paid less attention to the interactants' emotions, leaving age differences and underlying neural mechanisms unexplored. To address this gap, the present study combined functional and structural magnetic resonance imaging, employing a modified dictator game task with recipients displaying either neutral or sad facial expressions. Behavioral results indicated that although older adults' overall allocations did not differ significantly from those of young adults, older adults' allocations showing a decrease in emotion-related generosity compared to young adults. Using representational similarity analysis, we found that older adults showed reduced neural representations of recipients' emotions and gray matter volume in the right anterior cingulate gyrus (ACC), right insula, and left dorsomedial prefrontal cortex (DMPFC) compared to young adults. More importantly, mediation analyses indicated that age influenced allocations not only through serial mediation of neural representations of the right insula and left DMPFC, but also through serial mediation of the mean gray matter volume of the right ACC and left DMPFC. This study identifies the potential neural pathways through which age affects emotion-related social decision making, advancing our understanding of older adults' social interaction behavior that they may not be less generous unless confronted with individuals with specific emotions.

The Foundations and Practice of Neuropsychological Diagnostics in the Context of Forensic Psychiatric Examination

Background: cognitive impairments are comorbid for most mental disorders and can be important in assessing the ability of a subject to understand and control their actions in legally significant situations. The aim of review: аnalysis of neurobiological correlates and cognitive impairments in individuals suffering from mental disorders — organic personality disorder, schizophrenia, borderline personality disorder, in the context of forensic psychiatric examination. Material and methods: using keywords: “cognitive impairments in schizophrenia”, “cognitive impairments in organic personality disorders”, “cognitive impairments in personality disorders”, “MRI in schizophrenia”, “MRI in organic personality disorder”, “MRI in personality disorder”, “forensic neuropsychology”, “schizophrenia and criminal actions”, “organic personality disorders and criminal actions”, “personality disorders and criminal actions” the search and analysis of scientific publications was carried out in PubMed, Scopus, and RSCI databases over the past 5 years. Conclusion: schizophrenia shows deviations in the functioning of frontal and temporal lobes characterized by cognitive impairments: executive functions, attention, auditory-verbal memory, psychomotor slowness, inconsistent behavior, and deficits in volitional efforts. Borderline personality disorder is associated with reduced volume of the anterior cingulate gyrus, hippocampus, amygdala, and prefrontal cortex, dysfunctional interaction between limbic and prefrontal areas resulting in difficulties in emotion identification and impulsivity. Individuals with a history of traumatic brain injury (TBI) and secondary personality disorders exhibit diffuse gray matter damage affecting frontal, temporal, and parietal regions, emphasizing dysfunction of limbic-reticular complex structures with cognitive impairments including decreased thinking speed, attention stability, executive functions, auditory-verbal memory, visual-spatial memory, visual-motor coordination, and decreased impulse control. Individuals with mental disorders who commit criminal acts often exhibit deficiencies in frontal lobes and associated disturbances in executive components of mental activity, particularly cognitive flexibility and planning. Neuropsychological methods for studying cognitive functions can be used to obtain additional information in forensic psychiatric examinations.

Research progress on the mechanisms of pain empathy

AbstractRecent research has highlighted the indispensability of traditional molecular biology and imaging techniques in pain research. However, the mechanisms underlying pain empathy remain unclear. Consequently, a deeper understanding of these mechanisms would greatly enhance pain management. This article aimed to scrutinize previous research findings on pain empathy, with a particular emphasis on the correlation between empathy for pain and distinct anatomical structures, such as mirror neurons, the anterior cingulate cortex, insular cortex, prefrontal cortex, and amygdala. Additionally, this study explored the involvement of endogenous systems, including oxytocin and the locus coeruleus norepinephrine system, hypothalamic–pituitary–adrenal axis, opioid system, and 5‐hydroxylamine signaling. In conclusion, the mechanisms of pain empathy are complex and diverse, and research on pain empathy and target treatment will contribute to pain treatment.

Medial anterior prefrontal cortex stimulation downregulates implicit reactions to threats and prevents the return of fear.

Downregulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is critical for top-down modulatory processes, and despite previous studies adopting repetitive transcranial magnetic stimulation (rTMS) over this region provided encouraging results in enhancing extinction, no studies have hitherto explored the effects of stimulating the medial anterior PFC (aPFC, encompassing the Brodmann area 10) on threat memory and generalization. Here we showed that rTMS over the aPFC applied before threat memory retrieval immediately decreases implicit reactions to learned and novel stimuli in humans. These effects enduringly persisted 1 week later in the absence of rTMS. No effects were detected on explicit recognition. Critically, rTMS over the aPFC resulted in a more pronounced reduction of defensive responses compared to rTMS targeting the dorsolateral PFC. These findings reveal a previously unexplored prefrontal region, the modulation of which can efficiently and durably inhibit implicit reactions to learned threats. This represents a significant advancement toward the long-term deactivation of exaggerated responses to threats.

The relative brain signal variability increases in the behavioral variant of frontotemporal dementia and Alzheimer's disease but not in schizophrenia.

Overlapping symptoms between Alzheimer's disease (AD), behavioral variant of frontotemporal dementia (bvFTD), and schizophrenia (SZ) can lead to misdiagnosis and delays in appropriate treatment, especially in cases of early-onset dementia. To determine the potential of brain signal variability as a diagnostic tool, we assessed the coefficient of variation of the BOLD signal (CVBOLD) in 234 participants spanning bvFTD (n = 53), AD (n = 17), SZ (n = 23), and controls (n = 141). All underwent functional and structural MRI scans. Data unveiled a notable increase in CVBOLD in bvFTD patients across both datasets (local and international, p < 0.05), revealing an association with clinical scores (CDR and MMSE, r = 0.46 and r = -0.48, p < 0.0001). While SZ and control group demonstrated no significant differences, a comparative analysis between AD and bvFTD patients spotlighted elevated CVBOLD in the frontopolar cortices for the latter (p < 0.05). Furthermore, CVBOLD not only presented excellent diagnostic accuracy for bvFTD (AUC 0.78-0.95) but also showcased longitudinal repeatability. During a one-year follow-up, the CVBOLD levels increased by an average of 35% in the bvFTD group, compared to a 2% increase in the control group (p < 0.05). Our findings suggest that CVBOLD holds promise as a biomarker for bvFTD, offering potential for monitoring disease progression and differentiating bvFTD from AD and SZ.

Activation changes in patients with post-stroke cognitive impairment receiving intermittent theta burst stimulation: A functional near-infrared spectroscopy study.

Intermittent theta burst stimulation (iTBS) has demonstrated efficacy in patients with cognitive impairment. However, activation patterns and mechanisms of iTBS for post-stroke cognitive impairment (PSCI) remain insufficiently understood. To investigate the activation patterns and potential benefits of using iTBS in patients with PSCI. A total of forty-four patients with PSCI were enrolled and divided into an iTBS group (iTBS and cognitive training) or a control group (cognitive training alone). Outcomes were assessed based on the activation in functional near-infrared spectroscopy (fNIRS), as well as Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) and the modified Barthel Index (MBI). Thirty-eight patients completed the interventions and assessments. Increased cortical activation was observed in the iTBS group after the interventions, including the right superior temporal gyrus (STG), left frontopolar cortex (FPC) and left orbitofrontal cortex (OFC). Both groups showed significant improvements in LOTCA and MBI after the interventions (p < 0.05). Furthermore, the iTBS group augmented superior improvement in the total score of MBI and LOTCA compared to the control group, especially in visuomotor organization and thinking operations (p < 0.05). iTBS altered activation patterns and improved cognitive function in patients with PSCI. The activation induced by iTBS may contribute to the improvement of cognitive function.

Neural Representation of Valenced and Generic Probability and Uncertainty.

Representing the probability and uncertainty of outcomes facilitates adaptive behavior by allowing organisms to prepare in advance and devote attention to relevant events. Probability and uncertainty are often studied only for valenced (appetitive or aversive) outcomes, raising the question of whether the identified neural machinery also processes the probability and uncertainty of motivationally neutral outcomes. Here, we aimed to dissociate valenced from valence-independent (i.e., generic) probability (p; maximum at p = 1) and uncertainty (maximum at p = 0.5) signals using human neuroimaging. In a Pavlovian task (n = 41; 19 females), different cues predicted appetitive, aversive, or neutral liquids with different probabilities (p = 0, p = 0.5, p = 1). Cue-elicited motor responses accelerated, and pupil sizes increased primarily for cues that predicted valenced liquids with higher probability. For neutral liquids, uncertainty rather than probability tended to accelerate cue-induced responding and decrease pupil size. At the neural level, generic uncertainty signals were limited to the occipital cortex, while generic probability also activated the anterior ventromedial prefrontal cortex. These generic probability and uncertainty signals contrasted with cue-induced responses that only encoded the probability and uncertainty of valenced liquids in medial prefrontal, insular, and occipital cortices. Our findings show a behavioral and neural dissociation of generic and valenced signals. Thus, some parts of the brain keep track of motivational charge while others do not, highlighting the need and usefulness of characterizing the exact nature of learned representations.

Behavioral Bias for Exploration Is Associated with Enhanced Signaling in the Lateral and Medial Frontopolar Cortex.

Should we keep doing what we know works for us, or should we risk trying something new as it could work even better? The exploration-exploitation dilemma is ubiquitous in daily life decision-making, and balancing between the two is crucial for adaptive behavior. Yet, we only have started to unravel the neurocognitive mechanisms that help us to find this balance in practice. Analyzing BOLD signals of healthy young adults during virtual foraging, we could show that a behavioral tendency for prolonged exploitation was associated with weakened signaling during exploration in central node points of the frontoparietal attention network, plus the frontopolar cortex. These results provide an important link between behavioral heuristics that we use to balance between exploitation and exploration and the brain function that supports shifts from one tendency to the other. Importantly, they stress that interindividual differences in behavioral strategies are reflected in differences in brain activity during exploration and should thus be more in the focus of basic research that aims at delineating general laws governing visual attention.

Neuromodulation of inhibitory control using phase-lagged transcranial alternating current stimulation

BackgroundTranscranial alternating current stimulation (tACS) is a prominent non-invasive brain stimulation method for modulating neural oscillations and enhancing human cognitive function. This study aimed to investigate the effects of individualized theta tACS delivered in-phase and out-of-phase between the dorsal anterior cingulate cortex (dACC) and left dorsolateral prefrontal cortex (lDLPFC) during inhibitory control performance.MethodsThe participants engaged in a Stroop task with phase-lagged theta tACS over individually optimized high-density electrode montages targeting the dACC and lDLPFC. We analyzed task performance, event-related potentials, and prestimulus electroencephalographic theta and alpha power.ResultsWe observed significantly reduced reaction times following out-of-phase tACS, accompanied by reduced frontocentral N1 and N2 amplitudes, enhanced parieto-occipital P1 amplitudes, and pronounced frontocentral late sustained potentials. Out-of-phase stimulation also resulted in significantly higher prestimulus frontocentral theta and alpha activity.ConclusionsThese findings suggest that out-of-phase theta tACS potently modulates top-down inhibitory control, supporting the feasibility of phase-lagged tACS to enhance inhibitory control performance.

Dynamical and individualised approach of transcranial ultrasound neuromodulation effects in non-human primates

Low-frequency transcranial ultrasound stimulation (TUS) allows to alter brain functioning with a high spatial resolution and to reach deep targets. However, the time-course of TUS effects remains largely unknown. We applied TUS on three brain targets for three different monkeys: the anterior medial prefrontal cortex, the supplementary motor area and the perigenual anterior cingulate cortex. For each, one resting-state fMRI was acquired between 30 and 150 min after TUS as well as one without stimulation (control). We captured seed-based brain connectivity changes dynamically and on an individual basis. We also assessed between individuals and between targets homogeneity and brain features that predicted TUS changes. We found that TUS prompts heterogenous functional connectivity alterations yet retain certain consistent changes; we identified 6 time-courses of changes including transient and long duration alterations; with a notable degree of accuracy we found that brain alterations could partially be predicted. Altogether, our results highlight that TUS induces heterogeneous functional connectivity alterations. On a more technical point, we also emphasize the need to consider brain changes over-time rather than just observed during a snapshot; to consider inter-individual variability since changes could be highly different from one individual to another.

Information-based TMS to mid-lateral prefrontal cortex disrupts action goals during emotional processing

The ability to respond to emotional events in a context-sensitive and goal-oriented manner is essential for adaptive functioning. In models of behavioral and emotion regulation, the lateral prefrontal cortex (LPFC) is postulated to maintain goal-relevant representations that promote cognitive control, an idea rarely tested with causal inference. Here, we altered mid-LPFC function in healthy individuals using a putatively inhibitory brain stimulation protocol (continuous theta burst; cTBS), followed by fMRI scanning. Participants performed the Affective Go/No-Go task, which requires goal-oriented action during affective processing. We targeted mid-LPFC (vs. a Control site) based on the individualized location of action-goal representations observed during the task. cTBS to mid-LPFC reduced action-goal representations in mid-LPFC and impaired goal-oriented action, particularly during processing of negative emotional cues. During negative-cue processing, cTBS to mid-LPFC reduced functional coupling between mid-LPFC and nodes of the default mode network, including frontopolar cortex—a region thought to modulate LPFC control signals according to internal states. Collectively, these results indicate that mid-LPFC goal-relevant representations play a causal role in governing context-sensitive cognitive control during emotional processing.

Continuous decision to wait for a future reward is guided by fronto-hippocampal anticipatory dynamics.

Deciding whether to wait for a future reward is crucial for surviving in an uncertain world. While seeking rewards, agents anticipate a reward in the present environment and constantly face a trade-off between staying in their environment or leaving it. It remains unclear, however, how humans make continuous decisions in such situations. Here, we show that anticipatory activity in the anterior prefrontal cortex, ventrolateral prefrontal cortex, and hippocampus underpins continuous stay-leave decision-making. Participants awaited real liquid rewards available after tens of seconds, and their continuous decision was tracked by dynamic brain activity associated with the anticipation of a reward. Participants stopped waiting more frequently and sooner after they experienced longer delays and received smaller rewards. When the dynamic anticipatory brain activity was enhanced in the anterior prefrontal cortex, participants remained in their current environment, but when this activity diminished, they left the environment. Moreover, while experiencing a delayed reward in a novel environment, the ventrolateral prefrontal cortex and hippocampus showed anticipatory activity. Finally, the activity in the anterior prefrontal cortex and ventrolateral prefrontal cortex was enhanced in participants adopting a leave strategy, whereas those remaining stationary showed enhanced hippocampal activity. Our results suggest that fronto-hippocampal anticipatory dynamics underlie continuous decision-making while anticipating a future reward.

Different smartphone tasks and traffic complexity affect pedestrian awareness of co-existing road objects and cerebral oxygenation during shared space walking

Distraction, primarily owing to the widespread use of cell phones and mobile devices while walking, is a contributing factor to pedestrian injuries. Pedestrians distracted by smartphones exhibit decreased situational awareness, influenced by the nature of concurrent tasks. However, little is known about the neural correlations between smartphone use and pedestrian responses to safety–critical events in a walking environment. This study recruited 30 young adults to investigate pedestrians’ ability to selectively respond to road objects while using smartphones (texting and reading) while walking in an immersive virtual environment system. The level of traffic complexity for the road conditions was manipulated by varying the number of safety–critical road objects coexisting in the environment at any given time and the number of required responses to the number of objects. During each 7-min task condition, cerebral oxygenation was measured using functional near-infrared spectroscopy. Furthermore, smartphone task performance, response times to road objects, and perceived workload were also measured. The participants exhibited reduced texting speed and reading performance when responding sequentially to coexisting road objects. Compared with other road conditions, those requiring two responses to four objects resulted in an increased workload and longer object response times. Participants perceived a higher workload in conditions involving tasks with smartphones than those without smartphones. More importantly, increased concentrations of oxygenated hemoglobin in the prefrontal cortex were observed when participants were concurrently performing smartphone and pedestrian tasks. Compared to smartphone reading, smartphone texting induced greater cerebral oxygenation in the bilateral frontopolar cortex. These results suggest that continuously texting while walking may demand additional cognitive resources for executive function. The findings of this study represent an initial step towards elucidating the cognitive mechanisms underlying attentional impairments experienced during smartphone distraction and working towards a viable solution to mitigate pedestrian risk.

Smoking Progression and Nicotine-Enhanced Reward Sensitivity Predicted by Resting-State Functional Connectivity in Salience and Executive Control Networks.

The neural underpinnings underlying individual differences in nicotine-enhanced reward sensitivity (NERS) and smoking progression are poorly understood. Thus, we investigated whether brain resting-state functional connectivity (rsFC.) during smoking abstinence predicts NERS and smoking progression in young light smokers. We hypothesized that high rsFC between brain areas with high densities of nicotinic receptors (insula, anterior cingulate cortex [ACC], hippocampus, thalamus) and areas involved in reward-seeking (nucleus accumbens [NAcc], prefrontal cortex [PFC]) would predict NERS and smoking progression. Young light smokers (N = 64, age 18-24, M = 1.89 cigarettes/day) participated in the study. These individuals smoked between 5 and 35 cigarettes per week and lifetime use never exceeded 35 cigarettes per week. Their rsFC was assessed using functional magnetic resonance imaging after 14 hours of nicotine deprivation. Subjects also completed a probabilistic reward task after smoking a placebo on 1 day and a regular cigarette on another day. The probabilistic-reward-task assessed greater NERS was associated with greater rsFC between the right anterior PFC and right NAcc, but with reduced rsFC between the ACC and left inferior prefrontal gyrus and the insula and ACC. Decreased rsFC within the salience network (ACC and insula) predicted increased smoking progression across 18 months and greater NERS. These findings provide the first evidence that differences in rsFCs in young light smokers are associated with nicotine-enhanced reward sensitivity and smoking progression. NCT02129387 (preregistered hypothesis: www.clinicaltrials.gov). Weaker rsFC within the salience network predicted greater NERS and smoking progression. These findings suggest that salience network rsFC and drug-enhanced reward sensitivity may be useful tools and potential endophenotypes for reward sensitivity and drug-dependence research.