Responses In Prefrontal Cortex Research Articles

Why do mothers never stop grieving for their deceased children? Enduring alterations of brain connectivity and function.

A child’s death is a profound loss for mothers and affects hundreds of thousands of women. Mothers report inconsolable and progressive grief that is distinct from depression and impacts daily emotions and functions. The brain mechanisms responsible for this relatively common and profound mental health problem are unclear, hampering its clinical recognition and care. In an initial exploration of this condition, we used resting state functional MRI (fMRI) scans to examine functional connectivity in key circuits, and task-based fMRI to examine brain network activity in grieving mothers in response to pictures of their deceased child and as well as recognizable deceased celebrities and unfamiliar individuals. We compared nine mothers who had lost an adult child and aged-matched control mothers with a living child of a similar age. Additionally, we collected diffusion imaging scans to probe structural connectivity and complemented the imaging studies with neuropsychological assessments. Increased functional activation in Ventral Attention/Salience Networks accompanied by a reduced activation in the medial prefrontal cortex in response to the deceased child’s picture robustly distinguished the grieving mothers from controls. Heightened resting-state functional connectivity between the paraventricular thalamic nucleus (PVT) and the amygdala distinguished the grieving mothers from the controls and correlated with subjective grief severity. Structurally, maternal grief and its severity were associated with alterations in corticolimbic white matter tracts. Finally, grieving mothers performed worse than controls on neuropsychological tests of learning, memory, and executive function, linked with grief severity. Reduced activation in cortical regions inhibiting emotions and changes in the PVT circuitry—a region involved in long-term emotional memories and decision making under conflict—distinguish grieving mothers from controls. Notably, the magnitude of neurobiological changes correlates with the subjective severity of grief. Together, these new discoveries delineate a prevalent and under-recognized mental health syndrome and chart a path for its appreciation and care.

Prefrontal Cortex Response to Prenatal Insult and Postnatal Opioid Exposure.

The influence of proinflammatory challenges, such as maternal immune activation (MIA) or postnatal exposure to drugs of abuse, on brain molecular pathways has been reported. On the other hand, the simultaneous effects of MIA and drugs of abuse have been less studied and sometimes offered inconsistent results. The effects of morphine exposure on a pig model of viral-elicited MIA were characterized in the prefrontal cortex of males and females using RNA-sequencing and gene network analysis. Interacting and main effects of morphine, MIA, and sex were detected in approximately 2000 genes (false discovery rate-adjusted p-value < 0.05). Among the enriched molecular categories (false discovery rate-adjusted p-value < 0.05 and −1.5 > normalized enrichment score > 1.5) were the cell adhesion molecule pathways associated with inflammation and neuronal development and the long-term depression pathway associated with synaptic strength. Gene networks that integrate gene connectivity and expression profiles displayed the impact of morphine-by-MIA interaction effects on the pathways. The cell adhesion molecules and long-term depression networks presented an antagonistic effect between morphine and MIA. The differential expression between the double-challenged group and the baseline saline-treated Controls was less extreme than the individual challenges. The previous findings advance the knowledge about the effects of prenatal MIA and postnatal morphine exposure on the prefrontal cortex pathways.

Dosing Transcranial Magnetic Stimulation of the Primary Motor and Dorsolateral Prefrontal Cortices With Multi-Scale Modeling.

Transcranial magnetic stimulation (TMS) can depolarize cortical neurons through the intact skin and skull. The characteristics of the induced electric field (E-field) have a major impact on specific outcomes of TMS. Using multi-scale computational modeling, we explored whether the stimulation parameters derived from the primary motor cortex (M1) induce comparable macroscopic E-field strengths and subcellular/cellular responses in the dorsolateral prefrontal cortex (DLPFC). To this aim, we calculated the TMS-induced E-field in 16 anatomically realistic head models and simulated the changes in membrane voltage and intracellular calcium levels of morphologically and biophysically realistic human pyramidal cells in the M1 and DLPFC. We found that the conventional intensity selection methods (i.e., motor threshold and fixed intensities) produce variable macroscopic E-fields. Consequently, it was challenging to produce comparable subcellular/cellular responses across cortical regions with distinct folding characteristics. Prospectively, personalized stimulation intensity selection could standardize the E-fields and the subcellular/cellular responses to repetitive TMS across cortical regions and individuals. The suggested computational approach points to the shortcomings of the conventional intensity selection methods used in clinical settings. We propose that multi-scale modeling has the potential to overcome some of these limitations and broaden our understanding of the neuronal mechanisms for TMS.

Luxotonic signals in human prefrontal cortex as a possible substrate for effects of light on mood and cognition

Studies with experimental animals have revealed a mood-regulating neural pathway linking intrinsically photosensitive retinal ganglion cells (ipRGCs) and the prefrontal cortex (PFC), involved in the pathophysiology of mood disorders. Since humans also have light-intensity-encoding ipRGCs, we asked whether a similar pathway exists in humans. Here, functional MRI was used to identify PFC regions and other areas exhibiting light-intensity-dependent signals. We report 26 human brain regions having activation that either monotonically decreases or monotonically increases with light intensity. Luxotonic-related activation occurred across the cerebral cortex, in diverse subcortical structures, and in the cerebellum, encompassing regions with functions related to visual image formation, motor control, cognition, and emotion. Light suppressed PFC activation, which monotonically decreased with increasing light intensity. The sustained time course of light-evoked PFC responses and their susceptibility to prior light exposure resembled those of ipRGCs. These findings offer a functional link between light exposure and PFC-mediated cognitive and affective phenomena.

Long-term effects of multiple concussions on prefrontal cortex oxygenation during repeated squat-stands in retired contact sport athletes

ABSTRACT Background This study investigated the long-term effects of multiple concussions on prefrontal cortex oxygenation using near-infrared spectroscopy (NIRS) during a squat-stand maneuver that activated dynamic cerebral autoregulation. Methods Active male retired contact sport athletes with a history of 3+ concussions (mTBI; n = 55), and active retired athletes with no concussion history (CTRL; n = 29) were recruited. Participants completed a 5-min squat-stand maneuve (10-s squat, 10-s stand, 0.05 Hz; 15 times). Oxygenated (O2Hb), deoxygenated (HHb), total (tHb) hemoglobin, and hemoglobin difference (HbDiff) were analyzed through the change in maximal and minimal values during the test (∆MAX), Z-scores, and standard deviations. Results mTBI group showed left prefrontal cortex O2Hb ∆MAX (p = 0.046) and HbDiff ∆MAX (p = 0.018) were significantly higher. Within-group analyses showed significantly higher left HHb ∆MAX (p = 0.003) and lower left HbDiff Z-scores (p = 0.010) only in the mTBI group. The CTRL group demonstrated significantly lower left HbDiff SD (p = 0.039), tHb Z-scores (p = 0.030), and HbDiff ∆MAX (p = 0.037) compared to right prefrontal cortex response. Conclusion These preliminary results suggest changes in prefrontal cortex oxygenation potentially affecting the brain’s ability to adapt to changing cerebral perfusion pressure after multiple previous concussions.

Inferior temporal cortex leads prefrontal cortex in response to a violation of a learned sequence.

Primates learn statistical regularities that are embedded in visual sequences, a form of statistical learning. Single-unit recordings in macaques showed that inferior temporal (IT) neurons are sensitive to statistical regularities in visual sequences. Here, we asked whether ventrolateral prefrontal cortex (VLPFC), which is connected to IT, is also sensitive to the transition probabilities in visual sequences and whether the statistical learning signal in IT originates in VLPFC. We recorded simultaneously multiunit activity (MUA) and local field potentials (LFPs) in IT and VLPFC after monkeys were exposed to triplets of images with a fixed presentation order. In both areas, the MUA was stronger to images that violated the learned sequence (deviants) compared to the same images presented in the learned triplets. The high-gamma and beta LFP power showed an enhanced and suppressed response, respectively, to the deviants in both areas. The enhanced response was present also for the image following the deviant, suggesting a sensitivity for temporal adjacent dependencies in IT and VLPFC. The increased response to the deviant occurred later in VLPFC than in IT, suggesting that the deviant response in IT was not inherited from VLPFC. These data support predictive coding theories that propose a feedforward flow of prediction errors.

Associations Between Parenting Behavior and Neural Processing of Adolescent Faces in Mothers With and Without Depression

BackgroundThis study first examined how mothers with and without depression differ in neural activation in response to adolescents’ affective faces. Second, it examined the extent to which these neural activation patterns are related to observed positive and aggressive parenting behavior. MethodsMothers with and without depression (based on self-reported symptoms and treatment history; n = 77 and n = 64, respectively; meanage = 40 years) from low-income families completed an interaction task with their adolescents (meanage = 12.8 years), which was coded for parents’ aggressive and positive affective behavior. During functional magnetic resonance imaging, mothers viewed blurry, happy, sad, and angry faces of unfamiliar adolescents, with an instruction to either label the emotion or determine the clarity of the image. ResultsThe depression group showed less activation in the posterior midcingulate than the control subject group while labeling happy faces. Higher activation in the insula and dorsomedial prefrontal cortex (PFC) was related to less positive parenting behavior. Ventrolateral PFC activation was most pronounced when labeling negative emotions, but stronger ventrolateral PFC response to happy faces was associated with more aggressive parenting behavior. ConclusionsThis demonstrates the association between parents’ neural responses to adolescent faces and their behavior during interactions with their own adolescents, with relatively low insula and dorsomedial PFC activation supporting positive parenting and affect-dependent response in the ventrolateral PFC as being important to limit aggressive behavior.

Multi-modal assessment of reward functioning in adolescent anhedonia.

Anhedonia is a core symptom of depression that predicts worse treatment outcomes. Dysfunction in neural reward circuits is thought to contribute to anhedonia. However, whether laboratory-based assessments of anhedonia and reward-related neural function translate to adolescents' subjective affective experiences in real-world contexts remains unclear. We recruited a sample of adolescents (n = 82; ages 12-18; mean = 15.83) who varied in anhedonia and measured the relationships among clinician-rated and self-reported anhedonia, behaviorally assessed reward learning ability, neural response to monetary reward and loss (as assessed with functional magnetic resonance imaging), and repeated ecological momentary assessment (EMA) of positive affect (PA) and negative affect (NA) in daily life. Anhedonia was associated with lower mean PA and higher mean NA across the 5-day EMA period. Anhedonia was not related to impaired behavioral reward learning, but low PA was associated with reduced nucleus accumbens response during reward anticipation and reduced medial prefrontal cortex (mPFC) response during reward outcome. Greater mean NA was associated with increased mPFC response to loss outcome. Traditional laboratory-based measures of anhedonia were associated with lower subjective PA and higher subjective NA in youths' daily lives. Lower subjective PA and higher subjective NA were associated with decreased reward-related striatal functioning. Higher NA was also related to increased mPFC activity to loss. Collectively, these findings demonstrate that laboratory-based measures of anhedonia translate to real-world contexts and that subjective ratings of PA and NA may be associated with neural response to reward and loss.

Effects of acute exercise on craving and cortical hemodynamics under drug-cue exposure in MA-dependent individuals

BackgroundMethamphetamine (MA) dependent individuals who want to break free of their drug habit or guard against a relapse often find it hard to overcome cravings induced by drug-related cues they are bound to encounter. The purpose of this study was to investigate the effects of acute virtual reality (VR) enhanced physical exercise on cue-induced cravings in MA-dependent individuals. MethodsThirty MA-dependent individuals performed a drug-cue reactivity task both before and after a 10 min VR-enhanced competitive cycling exercise. Functional near-infrared spectroscopy (fNIRS) was recorded during the pre- and post-exercise drug-cue reactivity tasks. ResultsMA dependent individuals show higher hemodynamic responses in prefrontal cortex (PFC) to drug-related cues than to neutral cues. After acute exercise, hemodynamic responses in PFC, including bilateral dorsolateral prefrontal cortex and orbitofrontal cortex, were attenuated under the same drug-related cues exposure. Acute exercise also affected the functional connectivity between PFC and motor cortex in response to drug-related cues versus neutral cues. ConclusionsThese results suggest that a single session of VR-enhanced competitive cycling exercise facilitates MA-dependent individuals’ self-control over their cue-induced cravings by modulating cortical activations and brain functional networks.

Abnormal behavioral and neural responses in the right dorsolateral prefrontal cortex during emotional interference for cognitive control in pedophilic sex offenders

Studies within the last decade have reported neural and behavioral differences in cognitive control between men with the pedophilic disorder who commit (CSO+) and do not commit (CSO-) child sexual abuse. Prior studies reported a higher number of errors in Go/Nogo task and lower activity of the prefrontal cortex in NoGo trials, in CSO+ compared with CSO-. Moreover, negative mood was reported as a risk factor for child sexual abuse in pedophilic men. We aimed to examine differences in brain function and behavior between CSO+ and CSO- patients regarding emotional interference on cognitive processes and inhibition. We recruited CSO+ (n = 11) and CSO- (n = 14) patients as well as matched healthy controls (HC) (n = 17). Participants performed the affective Go/NoGo task in a block-design functional magnetic resonance imaging experiment. The task comprised the following four conditions: Negative Go, including only Go stimuli and negatively valenced pictures; Negative NoGo, including 50% of Go and 50% of NoGo trials as well as negatively valenced pictures; and two corresponding conditions with neutral pictures. Brain analysis was restricted to the dorsolateral prefrontal (DLPFC), orbitofrontal, and anterior cingulate cortices. The HC and CSO- groups, but not the CSO+ group, showed significantly slower reactions in negative blocks compared with neutral blocks. Brain analysis revealed increased activation in the right DLPFC during emotional interference contrast (Negative > Neutral) in the HC and CSO- groups; however, there was decreased activation in the CSO+ group. In the CSO+ group, negative distractors did not increase cognitive control processes, which was observed in the CSO- and HC groups at the behavioral and neural levels. These results support previous reports indicating offender status is associated with cognitive and emotional impairments.

P 58 EEG responses from direct cerebellar activation with Transcranial Magnetic Stimulation

Introduction: Measuring cortical responses from cerebellar stimulation might provide diagnostic biomarkers for the dentato-thalamo-cortical pathway's integrity. Recent studies have investigated the feasibility of delivering cerebellar stimulation through transcranial magnetic stimulation-electroencephalography (TMS-EEG). TMS-EEG presents several potential advantages and could provide more information than previous methods, which rely on motor output measures. However, past TMS-EEG studies were subject to considerable limitations, including contamination of the TMS-evoked potentials by peripherally-evoked potentials (PEPs). Therefore, we aimed to investigate cortical signatures of cerebellar stimulation, while controlling for confounding factors. Methods: We recruited 23 healthy, right-handed volunteers (13 females, mean ± SD age, 22.4±2.2 years). For each, resting motor threshold was used to titrate the intensity necessary to elicit a detectable cerebellar brain inhibition, which was set as the cerebellar TMS-intensity. A total of 280 single TMS pulses were then delivered to the cerebellum, 140 corresponding to REAL and 140 to SHAM condition. SHAM consisted of TMS to the right shoulder, whereas REAL consisted of both TMS to the right cerebellar hemisphere and to the right shoulder. Two further conditions were tested: TMS to the right occipital cortex and TMS to the right trapezius muscle, with otherwise the same parameters of the REAL condition. These conditions aimed to control for confounding factors, respectively collateral occipital cortex activation and PEPs from cerebellar TMS stimulation. EEG-signals of the different conditions were compared with respect to the evoked responses and changes in the time-frequency response via cluster-based t-tests. Results: Comparison of REAL and SHAM revealed significant differences. While some of these differences were explained by the occipital control stimulation, a left-hemispheric prefrontal early positive deflection at 20-26 ms and a left-hemispheric temporal negative deflection peaking at 45 ms (i.e. both contralateral to the cerebellar stimulation) were specific to the cerebellar stimulation. Furthermore, increased frontal theta power immediately after the TMS pulse was specific to the cerebellar stimulation. Conclusions: The investigation of multiple control conditions allowed for unmasking the cortical response resulting specifically from cerebellar TMS. The observed left-hemispheric prefrontal and subsequent temporal cortex responses were only present in conditions involving cerebellar stimulation and could neither be explained by collateral occipital stimulation, nor by a non-specific somatosensory input. These results are anatomically plausible, as targets of the dentato-thalamo-cortical pathway predominantly involve the contralateral prefrontal cortex and structural connectivity between the cerebellum and the contralateral superior temporal sulcus could be demonstrated in past studies.

An implicit priming intervention alters brain and behavioral responses to high-calorie foods: a randomized controlled study

Conditioned food cues (e.g., smell, sight) can affect intake of foods associated with those cues, regardless of homeostatic need. As such, altering automatic associations with food cues could support weight loss or maintenance efforts by affecting the salience of those cues and the effort required to resist consumption. This study investigated neuronal and behavioral effects of an implicit priming (IP) intervention, in which negatively valenced images were paired with high-calorie foods and positively valenced images with low-calorie foods. Priming images were presented immediately before food images, but below conscious perception (20ms). We hypothesized that this evaluative conditioning approach could alter food cue responses by modifying affective associations. The final sample included 41 adults with BMI≥25kg/m2 (n=22, active IP; n=19, control IP). In control IP, food images were primed with neutral, scrambled images. Participants completed a visual food cue task during fMRI, both before and after IP. To determine the replicability of prior behavioral findings, food image ratings were completed before and after IP as a secondary outcome. In a whole-brain analysis, reduced dorsolateral prefrontal cortex (dlPFC) response to high-calorie foods was observed after active compared with control IP (t=4.93, P=0.033). With a region of interest analysis, reduced response to high-calorie foods in active compared with control IP was also observed in the striatum (t=2.40, P=0.009) and insula (t=2.38, P=0.010). Active compared with control IP was associated with reduced high-calorie food ratings (F=4.70, P=0.038). Reduced insula and striatum response to high-calorie foods after active compared with control IP suggests effectiveness of IP in altering food cue salience. Reduced dlPFC response to high-calorie foods after active compared with control IP may reflect fewer attentional resources being directed to those images and reduced engagement of inhibitory processes.This trial was registered at clinicaltrials.gov as NCT02347527.

Prefrontal cortex hemodynamic response to acute high intensity intermittent exercise during executive function processing

We investigated prefrontal cortex (PFC) hemodynamic response, through functional near infrared spectroscopy (fNIRS) during executive function (EF) processing in response to acute high intensity intermittent exercise (HIIE) in young adults. We also assessed the associated sex differences in the cognitive scores and related PFC hemodynamic functions in response to HIIE. 49 young healthy adult participants (32 women, 17 men) were randomly assigned to either control or HIIE intervention groups. HIIE group participants performed 4 × 4 minutes of HIIE on cycle ergometer with 3 minutes of active recovery between the bouts; control group relaxed for the time equivalent to intervention. fNIRS data was collected during the performance of the EF tests including Color Word Stroop Test (CWST) and Trail Making Test (TMT) in pre and post sessions in both the groups. Results indicated a significant change in the hemodynamic response in the form of increased oxygenated and decreased deoxygenated hemoglobin in the PFC areas specific to the EF tasks, with improved CWST and TMT scores in response to HIIE intervention. PFC activation was different in men and women in response to HIIE, however similar scores of task performance were observed in men and women during the performance of executive functions in response to HIIE. The study concludes that an acute HIIE session improves executive function which is associated with an increase activation of PFC. Sex differences exist in the activation of PFC in response to HIIE during EF processing. Our study adds to the current evidence regarding exercise and cognition.

Adolescent rats respond differently to methylphenidate as compared to adult rats- concomitant VTA neuronal and behavioral Recordings

Methylphenidate (MPD) is the most widely prescribed psychostimulant used in adolescents and adults to treat attention-deficit/hyperactivity disorder (ADHD). The recreational use of MPD is becoming more prevalent because of its ability to improve cognitive enhancement. The ventral tegmental area (VTA) of the brain is highly associated with reward, cognition and addiction to drugs including psychostimulants like MPD. The VTA neuronal activity was recorded alongside the horizontal behavioral activity from freely behaving non-anesthetized rats. Four adolescent and four adult groups were treated with either saline, 0.6, 2.5 or 10.0 mg/kg MPD. In both adolescent and adult animals, the animals responded to MPD in a dose-dependent manner, such that as the dose of MPD increased, more animals and more VTA unit responded to the drug. The same doses of MPD elicited in some animals behavioral and neuronal sensitization and in other animals behavioral and neuronal tolerance. In the 0.6 and 10.0 mg/kg MPD dose groups there were significant differences between the age groups for how many animals expressed behavioral sensitization and behavioral tolerance to chronic MPD exposure. Additionally, the animal’s behavioral response to MPD by excitation or attenuation of activity did not always correlate to the VTA neuronal response, and the age group with significantly higher behavioral responses did not always correlate to the age group with significantly higher VTA neuronal responses for a given MPD dose. These findings differ from similar studies recorded from the prefrontal cortex (PFC), which exhibited behavioral responses continuously directly correlated to PFC responses for increasing MPD doses. This demonstrates that unlike other areas of the brain, there is not a direct relationship between VTA firing and behavioral activity, suggesting that there is input or modulation of this area from elsewhere in the brain. Further investigation is needed to clearly understand the relationship between VTA firing rates and behavioral responses to different MPD doses, especially given the significant differences in response between young and adult animals and the increasing use of the drug in adolescent populations.

Emotional voices modulate perception and predictions about an upcoming face

When we hear an emotional voice, does this alter how the brain perceives and evaluates a subsequent face? Here, we tested this question by comparing event-related potentials evoked by angry, sad, and happy faces following vocal expressions which varied in form (speech-embedded emotions, non-linguistic vocalizations) and emotional relationship (congruent, incongruent). Participants judged whether face targets were true exemplars of emotion (facial affect decision). Prototypicality decisions were more accurate and faster for congruent vs. incongruent faces and for targets that displayed happiness. Principal component analysis identified vocal context effects on faces in three distinct temporal factors: a posterior P200 (150–250 ms), associated with evaluating face typicality; a slow frontal negativity (200–750 ms) evoked by angry faces, reflecting enhanced attention to threatening targets; and the Late Positive Potential (LPP, 450–1000 ms), reflecting sustained contextual evaluation of intrinsic face meaning (with independent LPP responses in posterior and prefrontal cortex). Incongruent faces and faces primed by speech (compared to vocalizations) tended to increase demands on face perception at stages of structure-building (P200) and meaning integration (posterior LPP). The frontal LPP spatially overlapped with the earlier frontal negativity response; these components were functionally linked to expectancy-based processes directed towards the incoming face, governed by the form of a preceding vocal expression (especially for anger). Our results showcase differences in how vocalizations and speech-embedded emotion expressions modulate cortical operations for predicting (prefrontal) versus integrating (posterior) face meaning in light of contextual details.

Investigating the Influence of GABA Neurons on Dopamine Neurons in the Ventral Tegmental Area Using Optogenetic Techniques.

Dopamine (DA) is the key regulator of reward behavior. The DA neurons in the ventral tegmental area (VTA) and their projection areas, which include the prefrontal cortex (PFC), nucleus accumbens (NAc), and amygdala, play a primary role in the process of reward-driven behavior induced by the drugs of addiction, including nicotine and alcohol. In our previous study, we developed a novel platform consisting of micro-LED array devices to stimulate a large area of the brain of rats and monkeys with photo-stimulation and a microdialysis probe to estimate the DA release in the PFC. Our results suggested that the platform was able to detect the increased level of dopamine in the PFC in response to the photo-stimulation of both the PFC and VTA. In this study, we used this platform to photo-stimulate the VTA neurons in both ChrimsonR-expressing (non-specific) wild and dopamine transporter (DAT)-Cre (dopamine specific) mice, and measured the dopamine release in the nucleus accumbens shell (NAcShell). We measured the DA release in the NAcShell in response to optogenetic stimulation of the VTA neurons and investigated the effect of GABAergic neurons on dopaminergic neurons by histochemical studies. Comparing the photo-stimulation frequency of 2 Hz with that of 20 Hz, the change in DA concentration at the NAcShell was greater at 20 Hz in both cases. When ChrimsonR was expressed specifically for DA, the release of DA at the NAcShell increased in response to photo-stimulation of the VTA. In contrast, when ChrimsonR was expressed non-specifically, the amount of DA released was almost unchanged upon photo-stimulation. However, for nonspecifically expressed ChrimsonR, intraperitoneal injection of bicuculline, a competitive antagonist at the GABA-binding site of the GABAA receptor, also significantly increased the release of DA at the NAcShell in response to photo-stimulation of the VTA. The results of immunochemical staining confirm that GABAergic neurons in the VTA suppress DA activation, and also indicate that alterations in GABAergic neurons may have serious downstream effects on DA activity, NAcShell release, and neural adaptation of the VTA. This study also confirms that optogenetics technology is crucial to study the relationship between the mesolimbic dopaminergic and GABAergic neurons in a neural-specific manner.

Effects of family history of substance use disorder on reward processing in adolescents with and without attention-deficit/hyperactivity disorder.

Patients with attention‐deficit/hyperactivity disorder (ADHD) often develop early onset substance use disorder (SUD) and show poor treatment outcomes. Both disorders show similar reward‐processing alterations, but it is unclear whether these are associated with familial vulnerability to SUD. Our aim was to investigate effects of family history of SUD (FH) on reward processing in individuals with and without ADHD, without substance misuse. Behavioural and functional magnetic resonance imaging (fMRI) data from a modified monetary incentive delay task were compared between participants with and without FH (FH positive [FH+]: n = 76 and FH negative [FH−]: n = 69; 76 with ADHD, aged 16.74 ± 3.14, 82 males), while accounting for continuous ADHD scores. The main analysis showed distinct positive association between ADHD scores and reaction times during neutral versus reward condition. ADHD scores were also positively associated with anticipatory responses of dorsolateral prefrontal cortex, independent of FH. There were no main FH effects on brain activation. Yet, FH+ participants showed distinct neural alterations in ventrolateral prefrontal cortex (VLPFC), dependent on ADHD. This was driven by positive association between ADHD scores and VLPFC activation during reward outcome, only in FH+. Sensitivity analysis with stricter SUD index showed hyperactivation of anterior cingulate cortex for FH+, independent of ADHD, during reward anticipation. There were no FH or ADHD effects on activation of ventral striatum in any analysis. Findings suggest both FH and ADHD effects in circuits of reward and attention/memory during reward processing. Future studies should examine whether these relate to early substance use initiation in ADHD and explore the need for adjusted SUD prevention strategies.

Identification of \u22069-tetrahydrocannabinol (THC) impairment using functional brain imaging

The primary cannabinoid in cannabis, Δ9-tetrahydrocannabinol (THC), causes intoxication and impaired function, with implications for traffic, workplace, and other situational safety risks. There are currently no evidence-based methods to detect cannabis-impaired driving, and current field sobriety tests with gold-standard, drug recognition evaluations are resource-intensive and may be prone to bias. This study evaluated the capability of a simple, portable imaging method to accurately detect individuals with THC impairment. In this double-blind, randomized, cross-over study, 169 cannabis users, aged 18–55 years, underwent functional near-infrared spectroscopy (fNIRS) before and after receiving oral THC and placebo, at study visits one week apart. Impairment was defined by convergent classification by consensus clinical ratings and an algorithm based on post-dose tachycardia and self-rated “high.” Our primary outcome, prefrontal cortex (PFC) oxygenated hemoglobin concentration (HbO), was increased after THC only in participants operationalized as impaired, independent of THC dose. ML models using fNIRS time course features and connectivity matrices identified impairment with 76.4% accuracy, 69.8% positive predictive value (PPV), and 10% false-positive rate using convergent classification as ground truth, which exceeded Drug Recognition Evaluator-conducted expanded field sobriety examination (67.8% accuracy, 35.4% PPV, and 35.4% false-positive rate). These findings demonstrate that PFC response activation patterns and connectivity produce a neural signature of impairment, and that PFC signal, measured with fNIRS, can be used as a sole input to ML models to objectively determine impairment from THC intoxication at the individual level. Future work is warranted to determine the specificity of this classifier to acute THC impairment.ClinicalTrials.gov Identifier: NCT03655717

Sunk cost effects hinge on the neural recalibration of reference points in mental accounting.

The context of reinforcement history drastically influences human value-based choices. Mental accounting theory concerns how prior outcomes are perceived, combined and assigned into specific "mental" accounts to influence subsequent decisions but remains agnostic about the underlying computational and neural mechanisms. In a two-stage sequential decision-making task, we found previously incurred costs and bonuses biased subjects' choices in the opposite directions with similar magnitudes. Such effects were consistent with a computational model where the reference point was recalibrated by prior gains and losses encoded in the ventral striatum activities. Moreover, individual's susceptibility to prior outcomes was captured by the response of the dorsolateral prefrontal cortex and its functional connectivity with the medial orbitofrontal cortex, whose activity tracked the value of the chosen option. Our findings provide both behavioral and neural evidence of how sunk costs, benefits, and prospects are integrated within the mental accounting framework to influence choice behavior.

Prefrontal Cortex and Supplementary Motor Area Activation During Robot-Assisted Weight-Supported Over-Ground Walking in Young Neurological Patients: A Pilot fNIRS Study.

Introduction: Rehabilitation therapy devices are designed for practicing intensively task-specific exercises inducing long-term neuroplastic changes underlying improved functional outcome. The Andago enables over-ground walking with bodyweight support requiring relatively high cognitive demands. In this study, we investigated whether we could identify children and adolescents with neurological gait impairments who show increased hemodynamic responses of the supplementary motor area (SMA) or prefrontal cortex (PFC) measured with functional near-infrared spectroscopy (fNIRS) when walking in Andago compared to walking on a treadmill. We further assessed the practicability and acceptability of fNIRS.Methods: Thirteen participants (two girls, 11 boys, age 8.0–15.7 years) with neurological impairments walked in the Andago and on a treadmill under comparable conditions. We measured hemodynamic responses over SMA and PFC during 10 walks (each lasting 20 s.) per condition and analyzed the data according to the latest recommendations. In addition, we listed technical issues, stopped the time needed to don fNIRS, and used a questionnaire to assess acceptability.Results: Hemodynamic responses varied largely between participants. Participants with a typical hemodynamic response (i.e., increased oxygenated hemoglobin concentration) showed large cortical activations during walking in Andago compared to treadmill walking (large effect sizes, i.e., for SMA: r = 0.91, n = 4; for PFC: r = 0.62, n = 3). Other participants showed atypical (SMA: n = 2; PFC: n = 4) or inconclusive hemodynamic responses (SMA: n = 5; PFC: n = 4). The median time for donning fNIRS was 28 min. The questionnaire indicated high acceptance of fNIRS, despite that single participants reported painful sensations.Discussion: Repetitive increased activation of cortical areas like the SMA and PFC might result in long-term neuroplastic changes underlying improved functional outcome. This cross-sectional pilot study provides first numbers on hemodynamic responses in SMA and PFC during walking in Andago in children with neurological impairments, reveals that only a small proportion of the participants shows typical hemodynamic responses, and reports that fNIRS requires considerable time for donning. This information is needed when designing future longitudinal studies to investigate whether increased brain activation of SMA and PFC during walking in Andago could serve as a biomarker to identify potential therapy responders among children and adolescents undergoing neurorehabilitation.