Responses In Dorsolateral Prefrontal Cortex Research Articles

Effects of two-person synchronized cycling exercise on interpersonal cooperation: A near-infrared spectroscopy hyperscanning study

ObjectiveAlthough psychological research indicating the synchronous activities can promote interpersonal cooperation, thus far there is no direct evidence that two-person synchronous exercise effectively enhances interpersonal cooperative behaviors in Physical exercise field. This suggests that, although synchronization phenomenon is widespread in sports and is considered a potential tool for enhancing teamwork, its specific effects and functioning mechanisms still need to be clarified by further scientific research. This study intends to use two-person synchronized cycling exercise to investigate the synchronized exercise effect on interpersonal cooperative behavior and its underlying neural mechanisms. MethodsEighty college students without regular exercise habits will be randomly assigned to the experimental group (10 male dyads and 10 female dyads) and the control group (10 male dyads and 10 female dyads). During the experiment, dyads in the experimental group performed a 30-minute synchronized cycling exercise with synchronized pedaling movements; dyads in the control group rested sedentary in the same environment for 30 minutes. Interpersonal cooperative behavior was assessed with the Prisoner's Dilemma task, and the interpersonal neural synchronization(INS) data were collected in the prefrontal cortex using near-infrared hyperscanning. ResultsThis study compared behavior and brain activity before and after synchronous exercise. Behavioral results revealed that, compared to pre-exercise, dyads in the post-exercise had higher average cooperation rates, higher cooperation efficiency and shorter cooperation response times. Compared to post-sedentary, dyads in the post-exercise had shorter cooperation response times and higher cooperation efficiency. Furthermore, brain data showed that,compared to pre-exercise, dyads in the post-exercise had stronger INS in the dorsolateral prefrontal cortex(DLPFC), whereas the dyads in the post-exercise had stronge INS in the DLPFC compared to post-sedentary. After controlling for dyads' anxiety and mood states, this study also found a marginally significant negative correlation between INS differences in the left DLPFC and cooperation response time differences. ConclusionsThis research confirms, from both behavioral and neuroscience perspectives, that one synchronization cycle can significantly enhance interpersonal cooperative behavior, and this positive effect is closely associated with increased INS in the left DLPFC. This study provides new insights into understanding how positive interactive exercises promote interpersonal cooperation through specific neural mechanisms.

FTO variant is associated with changes in BMI, ghrelin, and brain function following bariatric surgery.

BACKGROUNDA polymorphism in the fat mass and obesity-associated gene (FTO) is linked to enhanced neural sensitivity to food cues and attenuated ghrelin suppression. Risk allele carriers regain more weight than noncarriers after bariatric surgery. It remains unclear how FTO variation affects brain function and ghrelin following surgery.METHODSResting-state functional magnetic resonance imaging and cue-reactivity functional magnetic resonance imaging with high-/low-caloric food cues were performed before surgery and at 1, 6, and 12 months after surgery to examine brain function in 16 carriers with 1 copy of the rs9939609 A allele (AT) and 26 noncarriers (TT). Behavioral assessments up to 5 years after surgery were also conducted.RESULTSThe AT group relative to the TT group had smaller BMI loss at 12-60 months after surgery and lower resting-state activity in posterior cingulate cortex following laparoscopic sleeve gastrectomy (group-by-time interaction effects). Meanwhile, the AT group relative to the TT group showed greater food cue responses in dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and insula (group effects). There were negative associations of weight loss with ghrelin and greater activation in DLPFC, DMPFC and insula in the AT but not the TT group.CONCLUSIONThese findings indicate that FTO variation is associated with the evolution of ghrelin signaling and brain function after bariatric surgery, which might hinder weight loss.TRIAL REGISTRATIONChinese Clinical Trial Registry Center, ChiCTR-OOB-15006346.FUNDINGThis work was supported by the National Natural Science Foundation of China (grant nos. 82172023, 82202252, 82302292); National Key R&D Program of China (no. 2022YFC3500603); Natural Science Basic Research Program of Shaanxi (grant nos. 2022JC-44, 2022JQ-622, 2023-JC-QN-0922, 2023-ZDLSF-07); Fundamental Research Funds for the Central Universities (grant nos. ZYTS23188, XJSJ23190, XJS221201, QTZX23093); and the Intramural Research Program of the National Institute on Alcoholism and Alcohol Abuse (grant no. Y1AA3009).

Sex differences in dorsolateral prefrontal cortical and superior colliculus activities support the impact of alcohol use severity and sleep deficiency on two-back memory.

Working memory refers to a process of temporary storage and manipulation of information to support planning, decision-making, and action. Frequently comorbid alcohol misuse and sleep deficiency have both been associated with working memory deficits. However, how alcohol misuse and sleep deficiency interact to impact working memory remains unclear. In this study, we aim to investigate the neural processes inter-relating alcohol misuse, sleep deficiency and working memory. We curated the Human Connectome Project (HCP) dataset and investigated the neural correlation of working memory in link with alcohol use severity and sleep deficiency in 991 young adults (521 women). The two were indexed by the first principal component (PC1) of principal component analysis of all drinking metrics and Pittsburgh Sleep Quality Index (PSQI) score, respectively. We processed the imaging data with published routines and evaluated the results with a corrected threshold. We used path model to characterize the inter-relationship between the clinical, behavioral, and neural measures, and explored sex differences in the findings. In whole-brain regression, we identified β estimates of dorsolateral prefrontal cortex response (DLPFC β) to 2- vs. 0-back in correlation with PC1. The DLPFC showed higher activation in positive correlation with PC1 across men and women (r=0.16, P<0.001). Path analyses showed the model PC1 → DLPFC β → differences in reaction time (2- minus 0-back; RT2-0) of correct trials → differences in critical success index (2- minus 0-back; CSI2-0) with the best fit. In women alone, in addition to the DLPFC, a cluster in the superior colliculus (SC) showed a significant negative correlation with the PSQI score (r=-0.23, P<0.001), and the path model showed the inter-relationship of PC1, PSQI score, DLPFC and SC β's, and CSI2-0 in women. Alcohol misuse may involve higher DLPFC activation in functional compensation, whereas, in women only, sleep deficiency affects 2-back memory by depressing SC activity. In women only, path model suggests inter-related impact of drinking severity and sleep deficiency on 2-back memory. These findings suggest potential sex differences in the impact of drinking and sleep problems on working memory that need to be further investigated.

Neural mechanisms of spatial auditory attention with magnified interaural level difference cues

Bilateral cochlear implant users struggle in spatial release from masking (SRM) tasks, likely due to restricted access to interaural time difference (ITD) cues. Instead, they must rely on interaural level difference (ILD) cues; however, our previous behavioral experiments suggest that magnification of ILDs can facilitate SRM. Here, we probed the neural mechanisms underlying the benefit of magnified ILDs. We tested 18 normal-hearing subjects in an anechoic chamber. Listeners heard target and masker sequences of object and color words from opposite (left and right) quarterfields and were asked to detect color words in the target stream. Both streams were spatialized using either 50 μS ITD (ITD50), 500 μS ITD (ITD500), a broadband 10 dB ILD (ILD10), or the largest naturally occurring frequency-specific ILD (70 degrees; ILD70n). We recorded task-elicited hemodynamic responses in dorsolateral prefrontal cortex (DLPFC) using functional Near-Infrared Spectroscopy. Subjects performed best in the ITD500 and ILD10 conditions. Hemodynamic response magnitudes were smaller for ITD50 than for all other conditions, consistent with frontal activity increasing when perceptual segregation is possible and spatial attention can be deployed successfully. These data show that magnified ILD cues enhance SRM and that the benefit ILDs confer arises because listeners can engage cognitive attentional processes.

Differential neural processing of value during decision-making in adults with attention-deficit/hyperactivity disorder and healthy controls.

Risk-taking behaviours are observed among adults with attention-deficit/hyperactivity disorder (ADHD). We sought to evaluate altered neural processing of stimuli values associated with risk-taking decision behaviour, distinct from learning requirements, among adults with ADHD. Overall, 32 adults with ADHD and 32 healthy controls without ADHD underwent a lottery choice task in a functional magnetic resonance imaging (fMRI) experiment. Participants accepted or rejected stakes with explicit information about variable probabilities of winning or losing points at different magnitudes. Outcomes were independent across trials, circumventing reward learning. Data analysis explored group differences in neurobehavioural responses to stimuli values during choice decision-making processing and outcome feedback. Compared with healthy controls, adults with ADHD had slower response times and tended to accept more stakes with a middle-to-low probability of winning. Adults with ADHD had evidence of lower dorsolateral prefrontal cortex (DLPFC) activity and reduced sensitivity in the ventromedial prefrontal cortex (VMPFC) region of interest in response to linear changes in probability, compared with healthy controls. Lower DLPFC responses were associated with lower VMPFC probability sensitivity and greater risk-taking among healthy controls but not adults with ADHD. Compared with health controls, adults with ADHD showed higher responses to loss outcomes in the putamen and hippocampus. Assessments of real-life decision behaviours are required to further validate the experimental findings. Our findings explore tonic and phasic neural processing of value-related information that modulates risk-taking behaviours among adults with ADHD. Dysregulated neural computation of the values of behavioural actions and outcomes in the frontostriatal circuits may underlie decision processing distinct from reward learning differences among adults with ADHD. NCT02642068.

TMS‐induced EEG perturbation as a marker of psychological resilience to deleterious mental health effects during the COVID‐19 pandemic

BackgroundSocial, economic and psychological hardships associated with the COVID‐19 pandemic are expected to result in a global burden on mental health outcomes. However, while some individuals suffer from increasing distress and reduced quality of life, others will show no negative effects. A better understanding of brain mechanisms subtending resilience would be helpful in informing future recommendations to individuals and societies facing the present pandemic and future similar events. Here, we compared neurophysiological brain markers between individuals who exhibited resilience or vulnerability to pandemic associated psychological stress.Method23 participants from the longitudinal study cohort of the Barcelona Brain Health Initiative (Cattaneo et al., Front. Aging Neurosci. 2018;10:321) who underwent concurrent transcranial magnetic stimulation with electroencephalography (TMS‐EEG), were classified as either resilient (n=16) or non‐resilient (n=7), based on their scoring in the PHQ‐4 questionnaire (Kroenke et al., Psychosomatics 2009;50(6):613–21) along four timepoints; one before COVID‐19 outbreak and three spanning 2.5 months during the pandemic. Individuals maintaining a score below 3 across all timepoints were deemed resilient, while those scoring below 3 before pandemic but higher than 2 at any pandemic timepoint were considered non‐resilient. TMS‐EEG data was collected by delivering 120 single TMS pulses to the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobule (IPL). TMS evoked global mean field amplitude and local response at the stimulation site were computed.ResultFigure 1 depicts time‐series for DLPFC and IPL responses for both groups of subjects. Overall, non‐resilient individuals exhibited a larger global response to TMS perturbation during DLPFC stimulation, as well as larger local current density estimates during IPL stimulation.ConclusionThese preliminary results revealed that non‐resilient individuals were more susceptible to TMS perturbation, shown by global DLPFC and local IPL reactivity. Notably, these targets are nodes of the default mode and cognitive control networks affected by stress (van Oort et al., Neurosci. Biobehav. Rev. 2017;83:281–97), and the left frontal cortex has been proposed as a cognitive resilience hub (Franzmeier et al., J. Alzheimer’s Dis. 2017;59(4):1381–92.). Future studies should investigate and confirm the possibility that these nodes constitute a shared neurophysiological substrate for psychological and cognitive resilience.

Use of Functional Near Infrared Spectroscopy to Assess Syntactic Processing by Monolingual and Bilingual Adults and Children.

This exploratory study assessed the use of functional Near Infrared Spectroscopy (fNIRS) to examine hemodynamic response patterns during sentence processing. Four groups of participants: monolingual English children, bilingual Chinese-English children, bilingual Chinese-English adults and monolingual English adults were given an agent selection syntactic processing task. Bilingual child participants were classified as simultaneous or sequential bilinguals to examine the impact of first language, age of second-language acquisition (AoL2A), and the length of second language experience on behavioral performance and cortical activation. Participants were asked to select the agent of four types of sentences: subject-verb-object (SVO), passive (PAS), subject-extracted relative clause (SR), and object-extracted relative clause (OR) adopted from the “Whatdunit” task by Montgomery et al. (2016). Semantic cues were removed by using inanimate nouns for agents and patients, which constrained participants to make decisions based on syntactic knowledge. Behavioral results showed greater accuracy for canonical SVO and SR sentence types than for noncanonical OR and PAS sentence types, which aligns with prior studies. Neuroimaging results revealed greater hemodynamic responses to relative clauses (i.e., SR and OR sentences) than to simple sentences (SVO and PAS), especially for Chinese-English bilinguals suggesting first-language transfer influencing sentence processing in English. The effects AoL2A and the length of second language experience showed no significant differences between simultaneous and sequential bilinguals or between bilingual adults and children for identifying the correct agent in each sentence. However, neuroimaging results demonstrated greater hemodynamic responses in right dorsolateral prefrontal cortex (DLPFC) and left inferior parietal lobule (IPL) in simultaneous bilinguals compared to sequential bilinguals and greater hemodynamic responses in left and right DLPFC and left IPL among bilingual adults. Different behavioral and neural hemodynamic response patterns afford new insights into the effects of syntactic knowledge on sentence processing.

Dorsolateral prefrontal cortex response to negative tweets relates to executive functioning.

Cognitive performance can become impaired when a stimulus evokes an emotional response. Social media often elicits emotional reactions, but, despite social media's ubiquity, cognitive and neural consequences of exposure to negative online content are relatively unknown. Fifty-seven human adults (18-29years; 38 female) who identified with at least one historically-marginalized group performed a novel 'Tweet Task'. While undergoing functional magnetic resonance imaging, participants completed a spatial reasoning task before and after reading a set of actual tweets. Participants were randomly assigned to read negative, discriminatory tweets from President Trump (Negative Condition) or neutral tweets (Neutral Condition). Participants in the Negative Condition reported worsening affect and demonstrated performance interference post-tweet compared to those in the Neutral Condition. Affect post-tweet was associated with parametric reductions in left dorsolateral prefrontal cortex, which predicted variance in performance beyond elicited negative affect. Performance effects were demonstrated on an unrelated spatial reasoning task suggesting that engaging with negative, emotionally-arousing content on social media can have deleterious effects on executive functioning in non-social domains.

Interaction of circulating GLP-1 and the response of the dorsolateral prefrontal cortex to food-cues predicts body weight development

ObjectivesThis study evaluated the impact of the interaction between the anorexigenic incretin hormone glucagon-like peptide-1 (GLP-1) and reward-related brain activity in the dorsolateral prefrontal cortex (DLPFC), a key area of behavioral control, on future weight loss in obese individuals. MethodsWe performed a weight loss-weight maintenance intervention study over 27 months. We applied an fMRI food-cue reactivity paradigm during which the participants were passively exposed to food pictures to evaluate neuronal activity in the DLPFC. Additionally, we measured concentrations of circulating GLP-1 levels during a standard oral glucose tolerance test. Phenotyping was performed consecutively before and after a 3-month low-calorie diet as well as after a randomized 12-month trial, investigating the effect of a combined behavioral intervention on body weight maintenance. Participants were then followed-up for another 12 months without further intervention. ResultsUsing voxel-wise linear mixed-effects regression analyses, we evaluated 56 measurements and identified a strong interaction between circulating, endogenous GLP-1 levels and DLPFC activity predicting body weight change over the total observation period (t = −6.17, p = 1.6 · 10−7). While neither the GLP-1 nor the DLPFC response individually predicted the subsequent weight change, participants achieved body weight loss when the GLP-1 and the DLPFC responses occurred concurrently. ConclusionsOur data demonstrate an interaction between a peripheral hormonal signal and central nervous activity as robust predictor of body weight change throughout the different periods of a long-term life-style intervention. The preeminent role of their interdependency compared to the partly ambivalent effects of the single components argues for integrative approaches to improve sensitivity and reliability of weight prediction conventionally based on individual biomarkers.

A Comparison of Auditory Oddball Responses in Dorsolateral Prefrontal Cortex, Basolateral Amygdala, and Auditory Cortex of Macaque

The mismatch negativity (MMN) is an ERP component seen in response to unexpected "novel" stimuli, such as in an auditory oddball task. The MMN is of wide interest and application, but the neural responses that generate it are poorly understood. This is in part due to differences in design and focus between animal and human oddball paradigms. For example, one of the main explanatory models, the "predictive error hypothesis", posits differences in timing and selectivity between signals carried in auditory and prefrontal cortex (PFC). However, these predictions have not been fully tested because (1) noninvasive techniques used in humans lack the combined spatial and temporal precision necessary for these comparisons and (2) single-neuron studies in animal models, which combine necessary spatial and temporal precision, have not focused on higher order contributions to novelty signals. In addition, accounts of the MMN traditionally do not address contributions from subcortical areas known to be involved in novelty detection, such as the amygdala. To better constrain hypotheses and to address methodological gaps between human and animal studies, we recorded single neuron activity from the auditory cortex, dorsolateral PFC, and basolateral amygdala of two macaque monkeys during an auditory oddball paradigm modeled after that used in humans. Consistent with predictions of the predictive error hypothesis, novelty signals in PFC were generally later than in auditory cortex and were abstracted from stimulus-specific effects seen in auditory cortex. However, we found signals in amygdala that were comparable in magnitude and timing to those in PFC, and both prefrontal and amygdala signals were generally much weaker than those in auditory cortex. These observations place useful quantitative constraints on putative generators of the auditory oddball-based MMN and additionally indicate that there are subcortical areas, such as the amygdala, that may be involved in novelty detection in an auditory oddball paradigm.

Reduced plasma ghrelin concentrations are associated with decreased brain reactivity to food cues after laparoscopic sleeve gastrectomy

The “hunger” hormone ghrelin regulates food-intake and preference for high-calorie (HC) food through modulation of the mesocortico-limbic dopaminergic pathway. Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery to treat morbid obesity. We tested the hypothesis that LSG-induced reductions in appetite and total ghrelin levels in blood are associated with reduced prefrontal brain reactivity to food cues. A functional magnetic resonance imaging (fMRI) cue-reactivity task with HC and low-calorie (LC) food pictures was used to investigate brain reactivity in 22 obese participants tested before and one month after bariatric surgery (BS). Nineteen obese controls (Ctr) without surgery were also tested at baseline and one-month later. LSG significantly decreased (1) fasting plasma concentrations of total ghrelin, leptin and insulin, (2) craving for HC food, and (3) brain activation in the right dorsolateral prefrontal cortex (DLPFC) in response to HC vs. LC food cues (PFWE < 0.05). LSG-induced reduction in DLPFC activation to food cues were positively correlated with reduction in ghrelin levels and reduction in craving ratings for food. Psychophysiological interaction (PPI) connectivity analyses showed that the right DLPFC had stronger connectivity with the ventral anterior cingulate cortex (vACC) after LSG, and changes in BMI were negatively correlated with changes in connectivity between the right DLPFC and vACC in the LSG group only. These findings suggest that LSG-induced weight-loss may be related to reductions in ghrelin, possibly leading to decreased food craving and hypothetically reducing DLPFC response to the HC food cues.

Effects of gymnemic acids lozenge on reward region response to receipt and anticipated receipt of high-sugar food.

A gymnemic acids lozenge that blocks sweet taste receptors reduced the decision to consume candy in humans even before the candy was tasted after the gymnemic acids dose, suggesting that blocking sweet taste receptors reduces valuation of sweet foods. The present study used functional magnetic resonance imaging (fMRI) to test whether the gymnemic acids lozenge reduces reward region response to both intake and anticipated intake of high-sugar food, as well as ad lib candy intake relative to a placebo lozenge. Here we show for the first time that a gymnemic acids lozenge versus placebo lozenge significantly reduced activation in the striatum and orbitofrontal cortex in response to anticipated tastes of high-sugar milkshake, and significantly reduced dorsolateral prefrontal cortex response to tastes of milkshake. We also replicated evidence that a gymnemic acids lozenge versus placebo lozenge significantly reduced ad lib candy intake. Results also provide novel evidence that an initial taste of a high-sugar food increases reward region (i.e., caudate) response to anticipated intake of more of the high-sugar food. Results suggest that blocking sweet taste receptors not only reduces reward region response to intake of high-sugar foods, but also reduces anticipated reward from high-sugar foods, potentially via a feedback loop regarding the availability of sweet taste receptors to convey perceptual input regarding sweet tastes. Collectively, results imply that the gymnemic acids lozenge might prove useful in decreasing high-sugar food intake.

Towards a biomarker model for cognitive improvement: No change in memory-related prefrontal engagement following a negative cognitive remediation trial in bipolar disorder

Cognitive deficits are prevalent in bipolar disorder during remission but effective cognition treatments are lacking due to insufficient insight into the neurobiological targets of cognitive improvement. Emerging data suggest that dorsal prefrontal cortex target engagement is a key neurocircuitry biomarker of pro-cognitive treatment effects. In this randomized controlled functional magnetic resonance imaging study, we test this hypothesis by investigating the effects of an ineffective cognitive remediation intervention on dorsal prefrontal response during strategic memory encoding and working memory engagement. Bipolar disorder patients in partial remission with subjective cognitive difficulties were randomized to receive 12-week group-based cognitive remediation ( n = 13) or to continue their standard treatment ( n = 14). The patients performed a strategic episodic picture encoding task and a spatial n-back working memory task under functional magnetic resonance imaging at baseline and following cognitive remediation or standard treatment. The right dorsolateral prefrontal cortex was commonly activated by both strategic memory tasks across all patients. The task-related prefrontal engagement was not altered by cognitive remediation relative to standard treatment. The dorsolateral prefrontal cortex response was not significantly associated with recall accuracy or working memory performance. As hypothesized, no task-related change in prefrontal activity was observed in a negative cognitive remediation trial in remitted bipolar disorder patients. By complementing previous findings linking cognitive improvement with increased dorsolateral prefrontal cortex engagement, our negative findings provide additional validity evidence to the dorsal prefrontal target engagement biomarker model of cognitive improvement by strengthening the proposed causality between modulation of dorsolateral prefrontal cortex engagement and pro-cognitive effects.

Weak dorsolateral prefrontal response to social criticism predicts worsened mood and symptoms following social conflict in people at familial risk for schizophrenia.

Understanding the specific mechanisms that explain why people who have relatives with schizophrenia (i.e., people at familial high risk; FHR) are more likely to develop the disorder is crucial for prevention. We investigated a diathesis-stress model of familial risk by testing whether FHR individuals under-recruit brain regions central to emotion regulation when exposed to social conflict, resulting in worse mood and symptoms following conflict. FHR and non-FHR participants listened to critical, neutral, and praising comments in an fMRI scanner before completing 4 weeks of daily-diary records. Compared to non-FHR individuals, FHR individuals under-recruited the bilateral dorsolateral prefrontal cortex (DLPFC)—a region strongly implicated in cognitive emotion regulation—following criticism. Furthermore, within FHR participants, weak DLPFC response to criticism in the laboratory task was associated with elevated negative mood and positive symptoms on days with distressing social conflicts in daily-diary assessments. Results extend diathesis-stress models of schizophrenia by clarifying neural and environmental pathways to dysregulation in FHR individuals.

Differential Recruitment of Brain Regions During Response Inhibition in Children Prenatally Exposed to Alcohol.

Response inhibition is a distinct aspect of executive function that is frequently impaired in children with fetal alcohol spectrum disorders (FASD). We used a Go/NoGo (GNG) task in a functional MRI protocol to investigate differential activation of brain regions in the response inhibition network in children diagnosed with full or partial fetal alcohol syndrome (FAS/PFAS), compared with healthy controls. A rapid, event-related task with 120 Go and 60 NoGo trials was used to study children aged 8 to 12years-8 with FAS/PFAS, 17 controls. Letters were projected sequentially, with Go and NoGo trials randomly interspersed across the task. BOLD signal in the whole brain was contrasted for the correct NoGo minus correct Go trials between the FAS/PFAS and control groups. Compared to the FAS/PFAS group, controls showed greater activation of the inferior frontal and anterior cingulate network linked to response inhibition in typically developing children. By contrast, the FAS/PFAS group showed greater BOLD response in dorsolateral prefrontal cortex and other middle prefrontal regions, suggesting compensation for inefficient function of pathways that normally mediate inhibitory processing. All group differences were significant after control for potential confounding variables. None of the effects of prenatal alcohol exposure on activation of the regions associated with response inhibition were attributable to the effects of this exposure on IQ. This is the first FASD GNG study in which all participants in the exposed group met criteria for a diagnosis of full FAS or PFAS. Although FASD is frequently comorbid with attention deficit hyperactivity disorder, the pattern of brain activation seen in these disorders differs, suggesting that different neural pathways mediate response inhibition in FASD and that different interventions for FASD are, therefore, warranted.

Disrupted avoidance learning in functional neurological disorder: Implications for harm avoidance theories.

BackgroundFunctional neurological disorder (FND) is an elusive disorder characterized by unexplained neurological symptoms alongside aberrant cognitive processing and negative affect, often associated with amygdala reactivity.MethodsWe examined the effect of negative conditioning on cognitive function and amygdala reactivity in 25 FND patients and 20 healthy volunteers (HV). Participants were first conditioned to stimuli paired with negative affective or neutral (CS +/CS −) information. During functional MRI, subjects then performed an instrumental associative learning task to avoid monetary losses in the context of the previously conditioned stimuli. We expected that FND patients would be better at learning to avoid losses when faced with negatively conditioned stimuli (increased harm avoidance). Multi-echo resting state fMRI was also collected from the same subjects and a robust denoising method was employed, important for removing motion and physiological artifacts.ResultsFND subjects were more sensitive to the negative CS + compared to HV, demonstrated by a reinforcement learning model. Contrary to expectation, FND patients were generally more impaired at learning to avoid losses under both contexts (CS +/CS −), persisting to choose the option that resulted in a negative outcome demonstrated by both behavioural and computational analyses. FND patients showed enhanced amygdala but reduced dorsolateral prefrontal cortex responses when they received negative feedback. Patients also had increased resting state functional connectivity between these two regions.ConclusionsFND patients had impaired instrumental avoidance learning, findings that parallel previous observations of impaired action-outcome binding. FND patients further show enhanced behavioural and neural sensitivity to negative information. However, this did not translate to improved avoidance learning. Put together, our findings do not support the theory of harm avoidance in FND. We highlight a potential mechanism by which negative contexts interfere with adaptive behaviours in this under-explored disorder.

Reorganization of Functional Networks in Verbal Working Memory Circuitry in Early Midlife: The Impact of Sex and Menopausal Status.

Converging preclinical and human evidence indicates that the decline in ovarian estradiol production during the menopausal transition may play a mechanistic role in the neuronal changes that occur early in the aging process. Here, we present findings from a population-based fMRI study characterizing regional and network-level differences in working memory (WM) circuitry in midlife men and women (N = 142; age range 46-53), as a function of sex and reproductive stage. Reproductive histories and hormonal evaluations were used to determine menopausal status. Participants performed a verbal WM task during fMRI scanning. Results revealed robust differences in task-evoked responses in dorsolateral prefrontal cortex and hippocampus as a function of women's reproductive stage, despite minimal variance in chronological age. Sex differences in regional activity and functional connectivity that were pronounced between men and premenopausal women were diminished for postmenopausal women. Critically, analyzing data without regard to sex or reproductive status obscured group differences in the circuit-level neural strategies associated with successful working memory performance. These findings underscore the importance of reproductive age and hormonal status, over and above chronological age, for understanding sex differences in the aging of memory circuitry. Further, these findings suggest that early changes in working memory circuitry are evident decades before the age range typically targeted in cognitive aging studies.

Dorsolateral Prefrontal Cortex Activity and Neuromodulation in Crack-Cocaine Dependents during Early Abstinence

Rationale: It is broadly known that addicted subjects have frontal dysfunction which is translated into: 1) low frontal activity in areas related to executive functions involved in the control over drug use; and 2) high frontal activity in areas related to incentive salience involved in the craving for drug use. Method: Electrical activity was correlated with days of abstinence and then sham-controlled session of transcranial direct current stimulation (tDCS) was performed in crack-cocaine users up to one month of abstinence. They were randomly divided to receive left cathodal/right anodal tDCS (20 min, 2 mA, 35 cm2) or sham procedure over the dorsolateral prefrontal cortex (DLPFC). Results: Absolute values from low-resolution brain electromagnetic tomography (LORETA) indicated that the activity in both left and right DLPFC increases progressively from the tenth day of abstinence. The left cathodal/right anodal tDCS prevented the increase of the activity in the left DLPFC facing crack-cocaine cue presentation in the visual P3 time window (350–600 ms). Spontaneous changes in the right DLPFC were not affected by tDCS. Conclusion: Prefrontal tDCS seems to modulate the DLPFC response to drug cue exposure in this preliminary study with crack-cocaine users suggesting this technique as an effective tool in reducing craving during early abstinence.

Successful antidepressant chronotherapeutics enhance fronto-limbic neural responses and connectivity in bipolar depression

The identification of antidepressant response predictors in bipolar disorder (BD) may provide new potential enhancements in treatment selection. Repeated total sleep deprivation combined with light therapy (TSD+LT) can acutely reverse depressive symptoms and has been proposed as a model antidepressant treatment. This study aims at investigating the effect of TSD+LT on effective connectivity and neural response in cortico-limbic circuitries during implicit processing of fearful and angry faces in patients with BD. fMRI and Dynamic Causal Modeling (DCM) were combined to study the effect of chronotherapeutics on neural responses in healthy controls (HC, n=35) and BD patients either responder (RBD, n=26) or non responder (nRBD, n=11) to 3 consecutive TSD+LT sessions. Twenty-four DCMs exploring connectivity between anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), Amygdala (Amy), fusiform gyrus and visual cortex were constructed. After treatment, patients significantly increased their neural responses in DLPFC, ACC and insula. nRBD showed lower baseline and endpoint neural responses than RBD. The increased activity in ACC and in medial prefrontal cortex, associated with antidepressant treatment, was positively associated with the improvement of depressive symptomatology. Only RBD patients increased intrinsic connectivity from DLPFC to ACC and reduced the modulatory effect of the task on Amy-DLPFC connection. A successful antidepressant treatment was associated with an increased functional activity and connectivity within cortico-limbic networks, suggesting the possible role of these measures in providing possible biomarkers for treatment efficacy.

Improved cerebral oxygenation response and executive performance as a function of cardiorespiratory fitness in older women: a fNIRS study.

Cardiorespiratory fitness has been shown to protect and enhance cognitive and brain functions, but little is known about the cortical mechanisms that underlie these changes in older adults. In this study, functional near infrared spectroscopy (fNIRS) was used to investigate variations in oxyhemoglobin [HbO2] and in deoxyhemoglobin [HHb] in the dorsolateral prefrontal cortex (DLPFC) during the performance of an executive control task in older women with different levels of cardiorespiratory fitness (VO2max). Thirty-four women aged 60–77 years were classified as high-fit and low-fit based on VO2max measures. They all performed a control counting (CNT) task and the Random Number Generation (RNG) task at two different paces (1 number/1 s and 1 number/1.5 s), allowing to manipulate task difficulty, while hemodynamic responses in the bilateral DLPFCs were recorded using continuous-wave NIRS. The behavioral data revealed that the high-fit women showed significantly better performance on the RNG tasks compared with the low-fit women. The high-fit women showed significant increases in [HbO2] responses in both left and right DLPFCs during the RNG task, while the low-fit women showed significantly less activation in the right DLPFC compared with the right DLPFC of the high-fit women and compared with their own left DLPFC. At the level of the whole sample, increases in the [HbO2] responses in the right DLPFC were found to mediate in part the relationship between VO2max level and executive performance during the RNG task at 1.5 s but not at 1 s. These results provide support for the cardiorespiratory fitness hypothesis and suggest that higher levels of aerobic fitness in older women are related to increased cerebral oxygen supply to the DLPFC, sustaining better cognitive performance.