The impact of anger on intertemporal decision-making in individuals with internet addiction: an fNIRS study.

Intertemporal decision-making is the choice between an immediate smaller reward (SS) and a delayed larger reward (LL). Intertemporal decision-making depends on the interaction of the cognitive and emotional systems, and the latter is particularly vital. According to the Appraisal Tendency Frame (ATF) theory, anger influences intertemporal decision-making by increasing an individual's sense of certainty and control. This study examined whether anger affects intertemporal decision-making in individuals with internet addiction (IA) in this manner and investigated its neural mechanisms. Nineteen individuals with IA and 20 healthy controls were recruited. All subjects performed the Monetary choice task under anger and neutral emotions while functional near-infrared spectroscopy (fNIRS) equipment simultaneously recorded the hemodynamics in the prefrontal cortex (PFC). Individuals with IA showed a more considerable delay discount and lower brain activations in the orbitofrontal cortex (OFC) and left dorsolateral prefrontal cortex (L-dlPFC) compared to HC. Moreover, individuals with IA made more LL choices in the angry condition than in the neutral emotion, yet there was no difference in HC. The brain activation in L-dlPFC of individuals with IA tends to increase in the angry condition compared to the neutral condition. These findings revealed that impairment of intertemporal decision-making in individuals with individuals with IA might be related to the dysfunction of OFC and L-dlPFC. Our work also provided initial footing for the applicability of the appraisal tendency frame theory to individuals with IA, and L-dlPFC might play a role in the effects of anger on intertemporal decision-making.

Assessment of the Effect of Meaningful Occupations on Motivation by Orbitofrontal Cortex Activation Using Near-Infrared Spectroscopy.

BACKGROUND: Meaningful occupations are those perceived as important by an individual. Research on meaningful occupations relies on subjective data and requires qualitative inquiries. Therefore, assessing the meaning of occupations using objective methods is challenging. As orbitofrontal cortex (OFC) activation is part of the reward system network involved in motivation, it could aid in assessing the meaning of occupations. OBJECTIVE: We aimed to investigate the effect of meaningful occupations on motivation by measuring OFC activation using near-infrared spectroscopy (NIRS). METHODS: Eight young and healthy participants were enrolled in this study. The occupation was set as "cooking," and its importance was confirmed using the Canadian Occupational Performance Measure (COPM). NIRS was performed using an OEG-16 (Spectareteh Inc.). The target task involved watching a cooking video, while the control task consisted of looking at a "+" sign on a blank sheet of paper. OFC activation was measured based on changes in oxygenated hemoglobin (oxy-Hb) concentration using a block design. Participants with COPM scores of eight or more were classified into the "meaningful occupation performance" group, while those with scores of seven or lower were classified into the "meaningful occupation non-performance" group. Changes in oxy-Hb concentrations between the two groups were compared using the Mann-Whitney U test. RESULTS: Four participants were assigned to the meaningful occupation group (frequency of implementation: various times per week for all participants), and four participants were assigned to the meaningful occupation non-performance group (frequency of implementation: various times per week for one participant, various times per month for one participant, and various times per year for two participants). Statistical analysis revealed significant differences in the changes in the oxy-Hb concentration in the left and bilateral OFC. CONCLUSION: This study suggests that it is important to focus on meaningful occupations that individuals consider important in order to activate the reward system and increase motivation.

Optogenetic Inhibition of the Orbitofrontal Cortex Disrupts Inhibitory Control during Stop-Change Performance in Male Rats.

Historically, the orbitofrontal cortex (OFC) has been implicated in a variety of behaviors ranging from reversal learning and inhibitory control to more complex representations of reward value and task space. While modern interpretations of the OFC's function have focused on a role in outcome evaluation, these cognitive processes often require an organism to inhibit a maladaptive response or strategy. Single-unit recordings from the OFC in rats performing a stop-change task show that the OFC responds strongly to STOP trials. To investigate the role that the OFC plays in stop-change performance, we expressed halorhodopsin (eNpHR3.0) in excitatory neurons in the OFC and tested rats on the stop-change task. Previous work suggests that the OFC differentiates between STOP trials based on trial sequence (i.e., gS trials: STOP trials preceded by a GO vs sS trials: STOP trials preceded by a STOP). We found that yellow light activation of the eNpHR3.0-expressing neurons significantly decreased accuracy only on STOP trials that followed GO trials (gS trials). Further, optogenetic inhibition of the OFC speeded reaction times on error trials. This suggests that the OFC plays a role in inhibitory control processes and that this role needs to be accounted for in modern interpretations of OFC function.

Adapting to Changes in Communication: The Orbitofrontal Cortex in Language and Speech Processing.

Despite most studies on the neurobiology of language demonstrating the central part of the perisylvian network involved in language and speech function, this review attempts to complement this view by focusing on the role of the orbitofrontal cortex (OFC). This region is primarily involved in goal-directed adaptive behavior. Recently, there has been increasing evidence that the OFC is involved in language and speech tasks. This review demonstrates that not only the linguistic tasks that involve the processing of socially, pragmatically and emotionally relevant information engage OFC and its neurobiological mechanisms, but also specific receptive and expressive language performances rely on specific neurophysiological properties of this region (e.g., the gray matter volume and the functional activation of OFC and the uncinate fasciculus that connects OFC), which in many cases, demand executive functions. These findings highlight: (1) The OFC plays a relevant role in the adaptive neurobiological function of language; (2) the neurobiological mechanisms beyond linguistic and speech processes complement and interplay with the language-unique processes to achieve successful comprehension and production in the changing communicative contexts.

Preliminary examination of the effects of an early parenting intervention on amygdala-orbitofrontal cortex resting-state functional connectivity among high-risk children: A randomized clinical trial.

We examined the long-term causal effects of an evidence-based parenting program delivered in infancy on children's emotion regulation and resting-state functional connectivity (rs-fc) during middle childhood. Families were referred to the study by Child Protective Services (CPS) as part of a diversion from a foster care program. A low-risk group of families was also recruited. CPS-involved families were randomly assigned to receive the target (Attachment and Biobehavioral Catch-up, ABC) or a control intervention (Developmental Education for Families, DEF) before infants turned 2. Both interventions were home-based, manualized, and 10-sessions long. During middle childhood, children underwent a 6-min resting-state functional MRI scan. Amygdala seed-based rs-fc analysis was completed with intervention group as the group-level predictor of interest. Fifty-seven children (NABC = 21; NDEF = 17; NCOMP = 19; Mage = 10.02 years, range = 8.08-12.14) were scanned successfully. The DEF group evidenced negative left amygdala↔OFC connectivity, whereas connectivity was near zero in the ABC and comparison groups (ABCvsDEF: Cohen's d = 1.17). ABC may enhance high-risk children's regulatory neurobiology outcomes ∼8 years after the intervention was completed.

Neural mechanisms of intertemporal and risky decision-making in individuals with internet use disorder: A perspective from directed functional connectivity.

Background and aims: The intertemporal and risk decision-making impairments are vital cognitive mechanisms in internet use disorder (IUD). However, the underlying neural mechanisms for these two decision-making dysfunctions in individuals with IUD remain unclear. Methods: This study employed Functional Near-Infrared Spectroscopy (fNIRS) to record changes in blood oxygen concentration in the prefrontal cortex of individuals with IUD during intertemporal and risk decision-making tasks. Results: The findings revealed that the intertemporal decision-making deficits in IUD group were primarily associated with reduced activation in the left dorsolateral prefrontal cortex (dlPFC) and orbitofrontal cortex (OFC) and FC from the left dlPFC to the right dlPFC. On the other hand, risk decision-making impairments were linked to decreased OFC activation and weakened functional connectivity from the left dlPFC to the right dlPFC and OFC. Discussions and Conslusions: These results suggested that while there were common neural mechanisms underlying intertemporal and risk decision-making impairments in individuals with IUD, specific neural foundations existed for each type of dysfunction.

Self-reported traumatic brain injury in a sample of impulsive violent offenders: neuropsychiatric correlates and possible "dose effects".

Background: Traumatic brain injury (TBI) is a major public health problem that may be associated with numerous behavioral problems, including impulsivity, aggression and violence. Rates of self-reported TBI are high within offender populations, but the extent to which TBI is causally implicated in causing illegal behavior is unclear. This study examined the psychological and functional correlates of histories of traumatic brain injury in a sample of impulsive violent offenders. Methods: Study participants, all men, had been recruited to participate in a randomized controlled trial of sertraline to reduce recidivism. Study entry criteria were an age of at least 18 years, a documented history of two or more violent offenses and a score of 70 or above on the Barratt Impulsiveness Scale. An extensive list of standardized questionnaires was administered to obtain information on previous TBI and other neuropsychiatric conditions or symptoms. Results: In the sample of 693 men, 66% were aged between 18 and 35 years old, and 55% gave a history of TBI ("TBI+"). Overall, 55% of study participants reported at least one TBI. High levels of neuropsychiatric symptomatology were reported. In 75% of TBI+ individuals, their most severe TBI (by self-report) was associated with loss of consciousness (LOC) < 30 min. Compared to TBI- (those without history of TBI) participants, TBI+ individuals were more impulsive (Eysenck Impulsivity), irritable, angry, and reported higher levels of assaultive behavior, depressive symptomology, alcohol use disorder, suicidal ideation, suicide attempts, and lower quality of life. Potential "dose effects" of TBI severity and frequency in terms of neuropsychiatric symptomatology were identified. Conclusion: Like other studies of offender populations, single and multiple TBIs were very common. The associations of TBI, TBI severity, and TBI frequency (i.e., TBI "burden") with adverse neuropsychiatric phenomena suggest TBI contributes importantly to offender morbidity but the select nature of the sample and cross-sectional study design constrain the interpretation of these findings.

Neuropsychiatric correlates of olfactory identification and traumatic brain injury in a sample of impulsive violent offenders.

Background: Olfactory deficits have a diverse etiology and can be detected with simple olfactory tests. Key olfactory pathways are located within the frontal and temporal lobes where they are vulnerable to damage due to head trauma. Orbitofrontal cortex (OFC) integrity is important for olfaction and aspects of behavioral regulation. We measured olfactory identification ability in a sample of impulsive violent offenders to determine its associations with history of traumatic brain injury (TBI) and a range of neuropsychiatric indices, including proxies for cognitive ability, impulsivity and social connectedness. Methods: Male participants were drawn from the ReINVEST study, a randomized controlled trial of sertraline to reduce recidivism in violent impulsive offenders. Criteria for participation in the study included a minimum age of 18 years, a documented history of two or more violent offenses, and a score of 70 or above on the Barratt Impulsiveness Scale (BIS-11). The 16-item "Sniffin sticks" (SS) odor identification test (OI) was administered as were standardized questionnaires regarding previous TBI, additional measures to screen cognition [word reading test of the Wechsler Individuals Achievement Test (WIAT), social connectedness (the Duke Social Support Scale), and a range of other neuropsychiatric conditions or symptoms]. The sample SS scores were compared against published age-specific norms. Univariate and multivariate analyses were performed with SS score (linear regression, within those without hyposmia) or hyposmia (logistic regression) as the outcome. Results: The mean OI scores were lower than population norms and 16% of participants were classified as hyposmic. Univariate analyses showed associations of SS score with age, WIAT score, impulsivity, TBI and TBI severity, social connectedness, childhood sexual abuse, suicidality and current use of heroin. In multivariate analyses, age, TBI severity and WIAT remained as significant independent predictors of SS score (within the normosmic range) or hyposmia (logistic regression). Conclusion: Olfactory performance was associated with multiple behavioral phenomena in a pattern that would be consistent with this serving as a proxy for orbitofrontal functioning. As such, OI testing may have utility in further studies of offenders. In future, we will examine whether olfactory score predicts recidivism or response to the administration of sertraline, in terms of reducing recidivism.

Evaluation of In Vitro Antioxidant, Anti-Obesity, and Anti-Diabetic Activities of Opuntia ficus Cladodes Gel and Its Application as a Preservative Coating for Shrimp during Refrigerated Storage.

Opuntia ficus cladodes (OFC) are considered one of the wastes that result from opuntia cultivation, and their disposal by traditional methods results in many environmental problems. Therefore, this study was conducted with two aims. The first was the production of OFC gel, and the evaluation of its in vitro antioxidant (by two methods, DPPH and ABTS), anti-obesity, and anti-diabetic activities. The second was an investigation of the effects of different concentrations of this gel (0, 50, and 100%) as an edible coating on the quality of shrimp during 8 days of refrigerated storage. The results showed that this gel was characterised by a high content of ash (10.42%), total carbohydrates (75.17%), and total phenols (19.79 mg GAE/g). OFC gel contained six types of sugars: arabinose, xylose, galactose, rhamnose, glucose, and uronic acid, and the most abundant was xylose (36.72%). It is also clear from the results that the OFC gel had high antioxidant properties, which were higher against DPPH than ABTS at the same concentration. OFC gel showed a high inhibition activity against lipase, α-glycosidase, and α-amylase enzymes, and their IC50 values were 1.43 mg/mL, 0.78 mg/mL, and 0.57 mg/mL, respectively. The results also stated that shrimp coated with OFC gel had lower pH, drip loss, TVB-N, and TBA values through the days of refrigerated storage. Moreover, the shrimp coated with 100% OFC gel were better than those coated with 50% OFC gel. In conclusion, OFC gel showed high potency as active antioxidant, for its enzyme anti-activities, and as an edible coating for shrimp.

Will Transcranial Magnetic Stimulation Improve the Treatment of Obsessive-Compulsive Disorder? A Systematic Review and Meta-Analysis of Current Targets and Clinical Evidence.

BACKGROUND: Although in 2017 a repetitive transcranial magnetic stimulation (rTMS) protocol received Food and Drug Administration approval for the first time for the treatment of obsessive-compulsive disorder (OCD), which neural target and which protocol should be used for OCD are still debated. The aim of the present study was to perform a systematic review and meta-analysis of the available open and sham-controlled trials. METHODS: The primary analysis included a pairwise meta-analysis (over 31 trials), and then subgroup analyses were performed for each targeted brain area. Meta-regression analyses explored the possible moderators of effect size. RESULTS: The pairwise meta-analysis showed a significant reduction in OCD symptoms following active rTMS (g = -0.45 [95%CI: -0.62, -0.29]) with moderate heterogeneity (I2 = 34.9%). Subgroup analyses showed a significant effect of rTMS over the bilateral pre-SMA (supplementary motor area), the DLPFC (dorsolateral prefrontal cortex), the ACC/mPFC (anterior cingulate cortex and medial prefrontal cortex), and the OFC (orbitofrontal cortex). No moderators of the effect size emerged. CONCLUSIONS: TMS of several brain targets represents a safe and effective treatment option for OCD patients. Further studies are needed to help clinicians to individualize TMS protocols and targets for each patient.

Role of hippocampus and orbitofrontal cortex in the association of interdependent self-construal with an acute stress response.

Empirical evidence indicates that high interdependent self-construal (InterSC) is correlated with exaggerated acute stress responses; however, the underlying neural correlates remain unclear. Considering the regulatory effect of the prefrontal cortex and limbic system on the acute stress response, the primary aim of this study was to investigate the role of the orbitofrontal cortex (OFC) and hippocampus (HIP) in the relationship between InterSC and acute stress responses. Forty-eight healthy college students underwent a modified version of the Montreal imaging stress task (MIST), while brain activity was recorded using functional magnetic resonance imaging (fMRI). Participants' saliva samples and subjective stress feelings were collected before, during, and after the MIST. Additionally, participants' self-construal was measured using questionnaires. Results revealed that InterSC was positively correlated with the activation of OFC, which, in turn, was associated with higher subjective stress feelings. A higher InterSC was also significantly associated with an enhanced salivary cortisol response in those with lower HIP activity. Furthermore, the HIP moderated the indirect effect of InterSC on subjective stress feelings by moderating the effect of InterSC on neural activity in the OFC. This indicated the mediation of the OFC was stronger in those with higher neural activity in the HIP than in those with lower activity in the HIP. In summary, the current study proposed an important role of the OFC-HIP regions in the relationship between InterSC and acute stress responses, making contribution to broadening the field of personality and stress and deepening our understanding of individual differences in acute stress responses.

Cortical Thickness of the Orbitofrontal Cortex in Patients with Alcohol Use Disorder.

AIMS: In the present study, it was hypothesised that compared to healthy control subjects, significant differences in the cortical thickness of the orbitofrontal cortex (OFC) region of the brain, which is relevant to both impulsivity and decision making, would be identified. METHODS: The subject groups included in the study were composed of 15 individuals who met the criteria for alcohol use disorder, according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM 5) diagnostic criteria based on the Structured Clinical Interview for DSM 5 (SCID), and were admitted to the Firat University School of Medicine Department of Psychiatry or were hospitalised, and 17 healthy control comparisons were made. The volumes of and cortical thickness of the OFC were measured in the subjects. RESULTS: It was found that patients with alcohol use disorder had reduced volumes of the OFC bilaterally and a thinner cortical thickness of the same region bilaterally compared to those of the healthy control comparisons. CONCLUSIONS: Consequently, it is suggested that the OFC region of the brain appears to be statistically significantly smaller in patients with alcohol use disorder, both in terms of cortical thickness and volume, compared to healthy controls. Future research should focus on the status of these relationships longitudinally and should assess the causality of the association with the treatment response.

A randomized, sham-controlled trial of high-definition transcranial direct current stimulation on the right orbital frontal cortex in children and adolescents with attention-deficit hyperactivity disorder.

Objective: This study aimed to find out the clinical and cognitive effects of high-definition transcranial direct current stimulation (HD-tDCS) on the right orbital frontal cortex (OFC) in the treatment of attention deficit hyperactivity disorder (ADHD). Methods: A total of 56 patients with ADHD were recruited as subjects and completely and randomly divided into the HD-tDCS group and the Sham group. A 1.0 mA anode current was applied to the right OFC. The HD-tDCS group received real stimulation, while the Sham group received sham stimulation in 10 sessions of treatment. ADHD symptom assessment (the SNAP-IV Rating Scale and the Perceived Stress Questionnaire) was carried out before treatment, after the 5th and 10th stimuli, and at the 6th week after the end of all stimulations, while the cognitive effect was assessed by the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT), the Stroop Color and Word Test (Stroop), and the Tower of Hanoi (TOH). Repeated-measure ANOVA was used to find out the results of both groups before and after treatment. Results: A total of 47 patients completed all sessions and evaluations. Their SNAP-IV score, their PSQ score, the mean visual and auditory reaction times by IVA-CPT, the interference RT of Stroop Color and Word, and the number of completed steps of TOH did not change with intervention time before and after treatment (P > 0.0031). However, the integrated visual and audiovisual commission errors and the TOH completion time results of the HD-tDCS group were significantly decreased after the 5th intervention, the 10th intervention, and the 6th week of intervention follow-up compared to the Sham group (P < 0.0031). Conclusion: This study draws cautious conclusions that HD-tDCS does not significantly alleviate the overall symptoms of patients with ADHD but leads to significant improvements in the cognitive measures of attention maintenance. The study also attempted to fill in the gaps in research studies on HD-tDCS stimulation of the right OFC. Clinical trial registration: ChiCTR2200062616.

The ventrolateral prefrontal cortex is part of the modular working memory system: A functional neuroanatomical perspective.

For many years, the functional role of the ventrolateral Pre-Frontal Cortex (PFC) was associated with executive functions, specifically in the context of non-affective cognitive processes. However, recent research has suggested that the ventrolateral PFC is also involved in the attention system. The Ben Shalom model of the functional organization of the prefrontal cortex (2019) posits that the ventrolateral PFC selects perceptual stimuli after integration by the adjacent ventromedial PFC. This article reviews the state-of-the-art findings to better understand the role of the ventrolateral PFC in the selection of perceptual information as grounded in the Ben Shalom model. Numerous studies have reported converging evidence for the selective role of this area. However, most argue that this perceptual selection takes place through the active updating of information values linked to goal-oriented actions. These studies thus view the ventrolateral PFC as part of a system that actively manipulates and changes processed information such as the working memory function, rather than being part of the attention system. In agreement with this view, this review suggests that this area is part of a complex and modular working memory system and illustrates with reference to Diamond's work on ADD. This working memory system is functionally and anatomically dispersed and includes the dorsolateral PFC, the ACC, the parietal cortex, the basal ganglia, and the cerebellum. Hence, future research should continue to explore the specific neurofunctional roles of these areas in working memory systems, and the connections between the different subareas in this complex array.

Geographical discrepancy in oral food challenge utilization based on Canadian billing data.

BACKGROUND: Oral food challenges (OFC) confer the highest sensitivity and specificity in diagnosis; however, uptake has been variable across clinical settings. Numerous barriers were identified in literature from inadequate training to resource access. OFC utilization patterns using billing data have not been previously studied. OBJECTIVE: The objective of this study is to explore the geographic differences in utilization of OFCs across Ontario and Québec using anonymized billing data from 2013 to 2017. METHODS: Anonymized OFC billing data were obtained between 2013 and 2017 from Ontario Health Insurance Plan (OHIP) and Régie de l'Assurance Maladie du Québec (RAMQ). The number of OFCs was extracted by location, billings, and physician demographics for clinic and hospital-based challenges. RESULTS: Over the period studied, the number of OFCs increased by 92% and 85% in Ontario clinics and Québec hospitals, respectively. For Ontario hospitals, the number of OFCs increased by 194%. While Québec performed exclusively hospital-based OFCs, after controlling for the population, the number of OFCs per 100,000 residents annually were similar to Ontario at 50 and 49 OFCs, respectively. The number of OFCs varied across the regions studied with an annual rate reaching up to 156 OFCs per 100,000 residents in urban regions and as low as 0.1 in regions furthest from city centers. CONCLUSION: OFC utilization has steadily increased over the last decade. There has been marked geographical discrepancies in OFC utilization which could be driven by the location of allergists and heterogeneity in their practices. More research is needed to identify barriers and propose solutions to them.

Morphometry of the lateral orbitofrontal cortex is associated with eating dispositions in early adolescence: findings from a large population-based study.

Early adolescence is a critical period for eating behaviors as children gain autonomy around food choice and peer influences increase in potency. From a neurodevelopmental perspective, significant structural changes take place in the prefrontal cortex during this time, including the orbitofrontal cortex (OFC), which is involved in socially contextualized decision-making. We examined the morphological features of the OFC in relation to food choice in a sample of 10 309 early adolescent children from the Adolescent Brain and Cognitive Development Study. Structural parameters of the OFC and insula were examined for relationships with two important aspects of food choice: limiting the consumption of fast/fried food and maximizing the consumption of nutritious foods. Raw, partially adjusted and fully adjusted models were evaluated. Findings revealed that a larger surface area of the lateral OFC was associated with higher odds of limiting fast/fried food consumption in raw [odds ratio (OR) = 1.07, confidence interval (CI): 1.02, 1.12, P = 0.002, PFDR = 0.012], partially adjusted (OR = 1.11, CI: 1.03, 1.19, P = 0.004, PFDR = 0.024) and fully adjusted models (OR = 1.11, CI: 1.03, 1.19, P = 0.006, PFDR = 0.036). In contrast, a larger insula volume was associated with lower odds of maximizing healthy foods in raw (OR = 0.94, CI: 0.91, 0.97, P <0.001, PFDR = 0.003) and partially adjusted (OR = 0.93, CI: 0.88, 0.98, P = 0.008, PFDR = 0.048) models. These findings refine our understanding of the OFC as a network node implicated in socially mediated eating behaviors.

Proprioceptive and Visual Feedback Responses in Macaques Exploit Goal Redundancy.

A common problem in motor control concerns how to generate patterns of muscle activity when there are redundant solutions to attain a behavioral goal. Optimal feedback control is a theory that has guided many behavioral studies exploring how the motor system incorporates task redundancy. This theory predicts that kinematic errors that deviate the limb should not be corrected if one can still attain the behavioral goal. Studies in humans demonstrate that the motor system can flexibly integrate visual and proprioceptive feedback of the limb with goal redundancy within 90 ms and 70 ms, respectively. Here, we show monkeys (Macaca mulatta) demonstrate similar abilities to exploit goal redundancy. We trained four male monkeys to reach for a goal that was either a narrow square or a wide, spatially redundant rectangle. Monkeys exhibited greater trial-by-trial variability when reaching to the wide goal consistent with exploiting goal redundancy. On random trials we jumped the visual feedback of the hand and found monkeys corrected for the jump when reaching to the narrow goal and largely ignored the jump when reaching for the wide goal. In a separate set of experiments, we applied mechanical loads to the arm of the monkey and found similar corrective responses based on goal shape. Muscle activity reflecting these different corrective responses were detected for the visual and mechanical perturbations starting at ∼90 and ∼70 ms, respectively. Thus, rapid motor responses in macaques can exploit goal redundancy similar to humans, creating a paradigm to study the neural basis of goal-directed motor action and motor redundancy.SIGNIFICANCE STATEMENT Moving in the world requires selecting from an infinite set of possible motor commands. Theories predict that motor commands are selected that exploit redundancies. Corrective responses in humans to either visual or proprioceptive disturbances of the limb can rapidly exploit redundant trajectories to a goal in <100 ms after a disturbance. However, uncovering the neural correlates generating these rapid motor corrections has been hampered by the absence of an animal model. We developed a behavioral paradigm in monkeys that incorporates redundancy in the form of the shape of the goal. Critically, monkeys exhibit corrective responses and timings similar to humans performing the same task. Our paradigm provides a model for investigating the neural correlates of sophisticated rapid motor corrections.

Efficacy of adjunctive intensive transcranial direct current stimulation of different cortices in treatment-resistant depression: a study protocol for a randomized double-blinded sham-controlled trial.

BACKGROUND: Treatment-resistant depression (TRD) carries a high economic burden worldwide. Transcranial direct current stimulation (tDCS) is advantageous for improving cognition and can be safely used in the treatment of depression. The effectiveness of tDCS of the left and right orbitofrontal cortex (OFC) as adjuvant treatment in patients with TRD has rarely been explored. Therefore, the objective of this trial is to evaluate the effectiveness there of when administering left dorsolateral prefrontal cortex (DLPFC) positive stimulation or OFC negative stimulation in patients with TRD. METHODS: Ninety eligible participants will be recruited to receive intervention at Shanghai Mental Health Center. Treatment will be randomly assigned in a double-blind fashion. Participants will receive either DLPFC (n = 30), OFC (n = 30), or sham (n = 30) tDCS, while continuing their usual pharmacotherapy at a stable dosage for at least 2 weeks before enrollment and throughout the stimulation period. All participants will receive 20 weekday stimulation sessions of 60 minutes duration each. Participants in the active group will be stimulated at 2 mA throughout the session, whereas the sham group will receive only a brief period of stimulation to mimic the sensation. After 20 stimulation sessions, no further treatment will be administered. Measurements will be conducted at regular points throughout and at 8 weeks after trial completion. The primary outcome is the change in the 17-item Hamilton Depression Rating Scale (HAMD-17) score after 20 sessions. Secondary outcomes were defined as changes in other measurement scales, cognitive function, resting-state functional magnetic resonance imaging (rs-fMRI), and serum biomarkers. DISCUSSION: We hypothesize that, in contrast to the sham group, both the active DLPFC and OFC tDCS groups will show superiority in HAMD-17 score reduction after 5, 10, and 20 sessions. Moreover, associations of the improvement of depressive symptoms with variations in rs-fMRI and TRD-related biomarkers will be evaluated. Our study may suggest that adjunctive intensive tDCS with left DLPFC positive stimulation or right OFC negative stimulation may be effective as a novel method to relieve depressive symptoms in patients with TRD. The variation of rs-fMRI, biomarkers could be used as a potential prediction model of treatment efficacy in TRD. TRIAL REGISTRATION: The trial protocol is registered with www.chictr.org.cn under protocol registration number ChiCTR2200058030. Date of registration: March 27, 2022. Recruitment started in September 2022 and is ongoing.

Individual differences in cocaine seeking during voluntary abstinence predicts cocaine relapse and the circuitry mediating relapse.

RATIONALE: There are no FDA-approved treatments to facilitate recovery from cocaine use disorder. Contingency management offers non-drug reinforcers to encourage abstinence and is effective at reducing drug seeking during treatment, but once discontinued, relapse rates increase. OBJECTIVES: We sought to establish a choice-based rodent model of voluntary abstinence (VA) from cocaine to test the ability of ceftriaxone, an antibiotic consistently shown to prevent relapse to cocaine seeking in rodents, to attenuate relapse after discontinuation of VA, and to investigate relapse-induced neuronal activation via c-Fos expression. METHODS: Male Sprague-Dawley rats self-administered sucrose pellets for 5 days and intravenous cocaine for 12 days. Rats then underwent 14 days of voluntary or forced abstinence. VA sessions entailed the opportunity to choose between sucrose and cocaine delivery in discrete trials (20 trials/day). Ceftriaxone (or vehicle) was administered during the last 7 days of abstinence. During a relapse test, only the cocaine-paired lever was available and presses on the lever delivered cocaine-paired cues. RESULTS: There were more presses on the sucrose lever during VA, but cocaine intake did not decline to zero. Ceftriaxone had no effect on cocaine intake during VA. Neither ceftriaxone nor VA reduced cocaine seeking during the relapse test, and cocaine intake during VA positively correlated with cocaine seeking during the test in vehicle-treated animals. Relapse-induced c-Fos expression was found to be greater in the ventral orbitofrontal cortex following VA. CONCLUSIONS: Sucrose availability leads to a decrease in, but not cessation of, cocaine seeking and a differential engagement of the circuitry underlying relapse.