Search

Animals, including humans, rely on contextual information to interpret ambiguous stimuli. Impaired context processing is a hallmark of several neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, post-traumatic stress disorder, and addiction. While sex differences in the prevalence and manifestations of these disorders are well established, potential sex differences in context processing remain uncertain. Here, we examined sex differences in the contextual control over cue-evoked reward seeking and its neural correlates, in rats. Male and female rats were trained in a bidirectional occasion-setting preparation in which the validity of two auditory reward-predictive cues was informed by the presence, or absence, of a visual contextual feature (LIGHT: X+/DARK: X-/LIGHT: Y-/DARK: Y+). Females were significantly slower to acquire contextual control over cue-evoked reward seeking. However, once established, the contextual control over behavior was more robust in female rats; it showed less within-session variability (less influence of prior reward) and greater resistance to acute stress. This superior contextual control achieved by females was accompanied by an increased activation of the orbitofrontal cortex (OFC) compared to males. Critically, these behavioral and neural sex differences were specific to the contextual modulation process and not observed in simple, context-independent, reward prediction tasks. These results indicate a sex-biased trade-off between the speed of acquisition and the robustness of performance in the contextual modulation of cued reward seeking. The different distribution of sexes along the fast learning ↔ steady performance continuum might reflect different levels of engagement of the OFC, and might have implications for our understanding of sex differences in psychiatric disorders.

Being touched by others (social-touch) and touching oneself (self-touch) are common nonverbal behaviors in everyday interaction. The commonalities and differences between these two types of touching behavior are of particular interest for conditions when social-touch is substantially restricted such as during the corona pandemic. Neuropsychologically, pleasant social-touch is associated with increased activation in frontal brain regions such as frontopolar, dorsolateral prefrontal (dlPFC), and orbitofrontal cortices (OFC). However, for these regions a deactivation has also been reported. Likewise, for self-touch the findings are controversial. Therefore, the aim of this study is to shed light on the controversial findings and to elucidate the relation between self-touch and social-touch. From 2021 to 2022, in a quasi-naturalistic setting, in forty-six participants brain oxygenation and deoxygenation was examined during social-touch and self-touch in frontal cortices applying functional NearInfraRed Spectroscopy (fNIRS). Social-touch compared to self-touch led to a significantly higher brain deoxygenation in the frontopolar areas and in parts of the dlPFC and OFC. In contrast, brain oxygenation in the PFC was significantly increased during self-touch compared to social-touch. The cerebral activation and deactivation pattern in a quasi-naturalistic setting indicates that self-touch cannot achieve the hedonic effects of social-touch, but it can influence internally self-regulating processes. [ABSTRACT FROM AUTHOR]

Elucidating biological mechanisms contributing to bipolar disorder (BD) is key to improved diagnosis and treatment development. With converging evidence implicating the metabotropic glutamate receptor 5 (mGlu5) in the pathology of BD, here, we therefore test the hypothesis that recently identified deficits in mGlu5 are associated with functional brain differences during emotion processing in BD. Positron emission tomography (PET) with [18F]FPEB was used to measure mGlu5 receptor availability and functional imaging (fMRI) was performed while participants completed an emotion processing task. Data were analyzed from 62 individuals (33 ± 12 years, 45 % female) who completed both PET and fMRI, including individuals with BD (n = 18), major depressive disorder (MDD: n = 20), and psychiatrically healthy comparisons (HC: n = 25). Consistent with some prior reports, the BD group displayed greater activation during fear processing relative to MDD and HC, notably in right lateralized frontal and parietal brain regions. In BD, (but not MDD or HC) lower prefrontal mGlu5 availability was associated with greater activation in bilateral pre/postcentral gyri and cuneus during fear processing. Furthermore, greater prefrontal mGlu5-related brain activity in BD was associated with difficulties in psychomotor function (r ≥ 0.904, p ≤ 0.005) and attention (r ≥ 0.809, p ≤ 0.028). The modest sample size is the primary limitation. Deficits in prefrontal mGlu5 in BD were linked to increased cortical activation during fear processing, which in turn was associated with impulsivity and attentional difficulties. These data further implicate an mGlu5-related mechanism unique to BD. More generally these data suggest integrating PET and fMRI can provide novel mechanistic insights. • Functional (fMRI) and molecular (PET) imaging performed in the same individuals with bipolar disorder (BD) and major depressive disorder (MDD). • Findings provide evidence of relationships between prefrontal mGlu5 and brain function during emotional processing that is unique to BD. • We propose a mechanism by which deficient prefrontal mGlu5 in BD contributes to alterations in clinically relevant brain function. • Understanding the role of mGlu5 in BD pathology could aid in the development of targeted, mechanistically informed treatments. [ABSTRACT FROM AUTHOR]

Background: Obstetric brachial plexus palsy (OBPP) is a condition impairing limb function caused by birth injury. In 20 to 30% of cases, severe OBPP can cause life constraints in feeding, grooming, and clothing tasks. Objective: The present study, using voxel- and surface-based morphometry (VBM and SBM), examined the brain structure of pediatric OBPP patients to better understand the effects of this peripheral motor deficit on early brain development. Methods: Thirty-six T1-weighted images of 18 patients (2-17 years old, mean age = 11.3, 8 females) and 18 healthy controls (2-17 years old, mean age = 10.1, 8 females) were collected for this study. MRI data were processed and analyzed using the Statistical Parametric Mapping 12 (SPM12) toolbox. The custom pediatric tissue probability map was created with the CerebroMatic (COM) toolbox. The results were considered significant if they survived whole-brain family-wise error correction (P <.05). Results: We have found differences in grey matter volumes in the bilateral anterior hippocampus (left P <.001 and right P =.01) and left cerebellum exterior (Crus I) (P <.001). We have also found differences in cortical thickness in the bilateral parahippocampal gyri (left P =.001 and right P =.005) and right orbitofrontal cortex (OFC) (P <.001). Conclusions: These structural differences might be linked to the altered environmental adaptation that children with OBPP face due to their primary motor deficit. Our findings hint at a complex interplay between motor capabilities, brain structure development, and cognitive functions. However, more research combining neuroimaging, behavioral, cognitive, and clinical data is needed to support stronger conclusions on this subject. [ABSTRACT FROM AUTHOR]

Abnormalities in cortical excitability and plasticity have been considered to underlie the pathophysiology of schizophrenia. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) can provide a direct evaluation of cortical responses to TMS. Here, we employed TMS-EEG to investigate cortical responses to orbitofrontal cortex (OFC) stimulation in schizophrenia. In total, we recruited 92 drug-naïve patients with first-episode schizophrenia and 51 age- and sex-matched healthy individuals. For each participant, one session of 1-Hz repetitive TMS (rTMS) was delivered to the right OFC, and TMS-EEG data were obtained to explore the change in cortical-evoked activities before and immediately after rTMS during the eyes-closed state. The MATRICS Consensus Cognitive Battery was used to assess neurocognitive performance. The cortical responses indexed by global mean field amplitudes (i.e., P30, N45, and P60) were larger in patients with schizophrenia than in healthy control participants at baseline. Furthermore, after one session of 1-Hz rTMS over the right OFC, the N100 amplitude was significantly reduced in the healthy control group but not in the schizophrenia group. In the healthy control participants, there was a significant correlation between modulation of P60 amplitude by rTMS and working memory; however, this correlation was absent in patients with schizophrenia. Aberrant global cortical responses following right OFC stimulation were found in patients with drug-naïve first-episode schizophrenia, supporting its significance in the primary pathophysiology of schizophrenia. [ABSTRACT FROM AUTHOR]

The ventral frontal cortex (VFC) in macaques is involved in many affective and cognitive processes and has a key role in flexibly guiding reward-based decision-making. VFC is composed of a set of anatomically distinct subdivisions that are within the orbitofrontal cortex, ventrolateral prefrontal cortex, and anterior insula. In part, because prior studies have lacked the resolution to test for differences, it is unclear if neural representations related to decision-making are dissociable across these subdivisions. Here we recorded the activity of thousands of neurons within eight anatomically defined subdivisions of VFC in male macaque monkeys performing a two-choice probabilistic task for different fruit juice outcomes. We found substantial variation in the encoding of decision variables across these eight subdivisions. Notably, ventrolateral Area 12l was unique relative to the other areas that we recorded from as the activity of single neurons integrated multiple attributes when monkeys evaluated the different choice options. Activity within Area 12o, in contrast, more closely represented reward probability and whether reward was received on a given trial. Orbitofrontal Area 11m/l contained more specific representations of the quality of the outcome that could be earned later on. We also found that reward delivery encoding was highly distributed across all VFC subdivisions, while the properties of the reward, such as its flavor, were more strongly represented in Areas 11m/l and 13m. Taken together, our work reveals the diversity of encoding within the various anatomically distinct subdivisions of VFC in primates. [ABSTRACT FROM AUTHOR]

• Sex-distinct responses to chronic restraint stress were shown in adolescent rats. • Stress persistently lowered body mass of male rats that continued into adulthood. • Stress temporarily reduced lean mass and delayed fat mass decrease in female rats. • Males sustained, but females abolished, HPA stress response measured by CORT levels. • RNA-Seq revealed sex-distinct genes in adolescent male and female brain subregions. Stress during adolescence clearly impacts brain development and function. Sex differences in adolescent stress-induced or exacerbated emotional and metabolic vulnerabilities could be due to sex-distinct gene expression in hypothalamic, limbic, and prefrontal brain regions. However, adolescent stress-induced whole-genome expression changes in key subregions of these brain regions were unclear. In this study, female and male adolescent Sprague Dawley rats received one-hour restraint stress daily from postnatal day (PD) 32 to PD44. Corticosterone levels, body weights, food intake, body composition, and circulating adiposity and sex hormones were measured. On PD44, brain and blood samples were collected. Using RNA-sequencing, sex-specific differences in stress-induced differentially expressed (DE) genes were identified in subregions of the hypothalamus, limbic system, and prefrontal cortex. Canonical pathways reflected well-known sex-distinct maladies and diseases, substantiating the therapeutic potential of the DE genes found in the current study. Thus, we proposed specific sex distinct, adolescent stress-induced transcriptional changes found in the current study as examples of the molecular bases for sex differences witnessed in stress induced or exacerbated emotional and metabolic disorders. Future behavioral studies and single-cell studies are warranted to test the implications of the DE genes identified in this study in sex-distinct stress-induced susceptibilities. [ABSTRACT FROM AUTHOR]

Chronic childhood stress is a prominent risk factor for developing affective disorders, yet mechanisms underlying this association remain unclear. Maintenance of optimal serotonin (5-HT) levels during early postnatal development is critical for the maturation of brain circuits. Understanding the long-lasting effects of early-life stress (ELS) on serotonin-modulated brain connectivity is crucial to develop treatments for affective disorders arising from childhood stress. Using a mouse model of chronic developmental stress, we determined the long-lasting consequences of ELS on 5-HT circuits and behavior in females and males. Using FosTRAP mice, we cross-correlated regional c-Fos density to determine brain-wide functional connectivity of the raphe nucleus. We next performed in vivo fiber photometry to establish ELS-induced deficits in 5-HT dynamics and optogenetics to stimulate 5-HT release to improve behavior. Adult female and male mice exposed to ELS showed heightened anxiety-like behavior. ELS further enhanced susceptibility to acute stress by disrupting the brain-wide functional connectivity of the raphe nucleus and the activity of 5-HT neuron population, in conjunction with increased orbitofrontal cortex (OFC) activity and disrupted 5-HT release in medial OFC. Optogenetic stimulation of 5-HT terminals in the medial OFC elicited an anxiolytic effect in ELS mice in a sex-dependent manner. These findings suggest a significant disruption in 5-HT–modulated brain connectivity in response to ELS, with implications for sex-dependent vulnerability. The anxiolytic effect of the raphe–medial OFC circuit stimulation has potential implications for developing targeted stimulation-based treatments for affective disorders that arise from early life adversities. [ABSTRACT FROM AUTHOR]

During natural behavior, an action often needs to be suddenly stopped in response to an unexpected sensory input—referred to as reactive stopping. Reactive stopping has been mostly investigated in humans, which led to hypotheses about the involvement of different brain structures, in particular the hyperdirect pathway. Here, we directly investigate the contribution and interaction of two key regions of the hyperdirect pathway, the orbitofrontal cortex (OFC) and subthalamic nucleus (STN), using dual-area, multielectrode recordings in male rats performing a stop-signal task. In this task, rats have to initiate movement to a go-signal, and occasionally stop their movement to the go-signal side after a stop-signal, presented at various stop-signal delays. Both the OFC and STN show near-simultaneous field potential reductions in the beta frequency range (12–30 Hz) compared with the period preceding the go-signal and the movement period. These transient reductions (∼200 ms) only happen during reactive stopping, which is when the stop-signal was received after action initiation, and are well timed after stop-signal onset and before the estimated time of stopping. Phase synchronization analysis also showed a transient attenuation of synchronization between the OFC and STN in the beta range during reactive stopping. The present results provide the first direct quantification of local neural oscillatory activity in the OFC and STN and interareal synchronization specifically timed during reactive stopping. [ABSTRACT FROM AUTHOR]

Self-ambivalence, a prevalent phenomenon in daily life, has been increasingly substantiated by research. It refers to conflicting self-views and evaluations, primarily concerning self-worth and morality. Previous behavioral research has distinguished self-worth and moral ambivalence, but it remains unclear whether they have separable neural bases. The present study addressed this question by examining resting-state brain activity (i.e., the fractional amplitude of low-frequency fluctuations, fALFF) and connectivity (i.e., resting-state functional connectivity, RSFC) in 112 college students. The results found that self-worth ambivalence was positively related to the fALFF in the orbitofrontal cortex (OFC) and left superior parietal lobule (SPL). The RSFC strength between the SPL and precuneus/posterior cingulate cortex (PCC) was positively related to self-worth ambivalence. Moral ambivalence was positively associated with the fALFF in the left SPL (extending into the temporoparietal junction) and right SPL. The RSFC strengths between the left SPL/TPJ and OFC, as well as the RSFC strengths between the right SPL as a seed and the bilateral middle and inferior temporal gyrus, were associated with moral ambivalence. Overall, the neural bases of self-worth and moral ambivalence are associated with the SPL and OFC, involved in attentional alertness and value representation, respectively. Additionally, the neural basis of moral ambivalence is associated with the TPJ, responsible for mentalizing. [ABSTRACT FROM AUTHOR]

Although aversive responses to sensory stimuli are common in autism spectrum disorder (ASD), it remains unknown whether the social relevance of aversive sensory inputs affects their processing. We used functional magnetic resonance imaging (fMRI) to investigate neural responses to mildly aversive nonsocial and social sensory stimuli as well as how sensory over‐responsivity (SOR) severity relates to these responses. Participants included 21 ASD and 25 typically‐developing (TD) youth, aged 8.6–18.0 years. Results showed that TD youth exhibited significant neural discrimination of socially relevant versus irrelevant aversive sensory stimuli, particularly in the amygdala and orbitofrontal cortex (OFC), regions that are crucial for sensory and social processing. In contrast, ASD youth showed reduced neural discrimination of social versus nonsocial stimuli in the amygdala and OFC, as well as overall greater neural responses to nonsocial compared with social stimuli. Moreover, higher SOR in ASD was associated with heightened responses in sensory‐motor regions to socially‐relevant stimuli. These findings further our understanding of the relationship between sensory and social processing in ASD, suggesting limited attention to the social relevance compared with aversiveness level of sensory input in ASD versus TD youth, particularly in ASD youth with higher SOR. Lay Summary: In this study, we used functional magnetic resonance imaging (fMRI) to examine brain responses to aversive sensory stimuli with and without social relevance in youth with autism spectrum disorder (ASD) and typically‐developing (TD) youth. TD youth showed greater neural responses to social compared with nonsocial sensory inputs, whereas the opposite was true in ASD youth. Results suggest that compared with TD youth, ASD youth (particularly those with more severe sensory over‐responsivity symptoms) attend more to the level of aversiveness rather than to the social relevance of sensory input. [ABSTRACT FROM AUTHOR]

Individuals with high emotional granularity make fine-grained distinctions between their emotional experiences. To have greater emotional granularity, one must acquire rich conceptual knowledge of emotions and use this knowledge in a controlled and nuanced way. In the brain, the neural correlates of emotional granularity are not well understood. While the anterior temporal lobes, angular gyri, and connected systems represent conceptual knowledge of emotions, inhibitory networks with hubs in the inferior frontal cortex (i.e., posterior inferior frontal gyrus, lateral orbitofrontal cortex, and dorsal anterior insula) guide the selection of this knowledge during emotions. We investigated the structural neuroanatomical correlates of emotional granularity in 58 healthy, older adults (ages 62-84 years), who have had a lifetime to accrue and deploy their conceptual knowledge of emotions. Participants reported on their daily experience of 13 emotions for 8 weeks and underwent structural magnetic resonance imaging. We computed intraclass correlation coefficients across daily emotional experience surveys (45 surveys on average per participant) to quantify each participant's overall emotional granularity. Surface-based morphometry analyses revealed higher overall emotional granularity related to greater cortical thickness in inferior frontal cortex (pFWE < 0.05) in bilateral clusters in the lateral orbitofrontal cortex and extending into the left dorsal anterior insula. Overall emotional granularity was not associated with cortical thickness in the anterior temporal lobes or angular gyri. These findings suggest individual differences in emotional granularity relate to variability in the structural neuroanatomy of the inferior frontal cortex, an area that supports the controlled selection of conceptual knowledge during emotional experiences.

Abstract Background Transcranial magnetic stimulation (TMS) (including the theta burst stimulation (TBS) form of TMS used in this study) is a non-invasive means to stimulate nerve cells in superficial areas of the brain. In recent years, there has been a growth in the application of TMS to investigate the modulation of neural networks involved in substance use disorders. This study examines the feasibility of novel TMS protocols for the treatment of methamphetamine (MA) use disorder in an ambulatory drug and alcohol treatment setting. Methods Thirty participants meeting the criteria for moderate to severe MA use disorder will be recruited in community drug and alcohol treatment settings and randomised to receive active TMS or sham (control) intervention. The treatment is intermittent TBS (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC), then continuous TBS (cTBS) to the left orbitofrontal cortex (OFC). Twelve sessions are administered over 4 weeks with opt-in weekly standardized cognitive behaviour therapy (CBT) counselling and a neuroimaging sub-study offered to participants. Primary outcomes are feasibility measures including recruitment, retention and acceptability of the intervention. Secondary outcomes include monitoring of safety and preliminary efficacy data including changes in substance use, cravings (cue reactivity) and cognition (response inhibition). Discussion This study examines shorter TBS protocols of TMS for MA use disorder in real-world drug and alcohol outpatient settings where withdrawal and abstinence from MA, or other substances, are not eligibility requirements. TMS is a relatively affordable treatment and staff of ambulatory health settings can be trained to administer TMS. It is a potentially scalable and translatable treatment for existing drug and alcohol clinical settings. TMS has the potential to provide a much-needed adjuvant treatment to existing psychosocial interventions for MA use disorder. A limitation of this protocol is that the feasibility of follow-up is only examined at the end of treatment (4 weeks). Trial registration Australia New Zealand Clinical Trial Registry ACTRN12622000762752. Registered on May 27, 2022, and retrospectively registered (first participant enrolled) on May 23, 2022, with protocol version 7 on February 24, 2023.

Dopamine (DA) plays a pivotal role in reward processing, cognitive functions, and emotional regulation. The prefrontal cortex (PFC) is a critical brain region for these processes. Parvalbumin-positive (PV+) neurons are one of the major classes of inhibitory GABAergic neurons in the cortex, they modulate the activity of neighboring neurons, influencing various brain functions. While DA receptor expression exhibits age-related changes, the age-related changes of these receptors in PV+ neurons, especially in the PFC, remain unclear. To address this, we investigated the expression of DA D1 (D1R) and D2 (D2R) receptors in PV+ neurons within the orbitofrontal (OFC) and prelimbic (PrL) cortices at different postnatal ages (P28, P42, P56, and P365). We found that the expression of D1R and D2R in PV+ neurons showed both age- and region-related changes. PV+ neurons in the OFC expressed a higher abundance of D1 than those in the PrL, and those neurons in the OFC also showed higher co-expression of D1R and D2R than those in the PrL. In the OFC and PrL, D1R in PV+ neurons increased from P28 and reached a plateau at P42, then receded to express at P365. Meanwhile, D2R did not show significant age-related changes between the two regions except at P56. These results showed dopamine receptors in the prefrontal cortex exhibit age- and region-specific changes, which may contribute to the difference of these brain regions in reward-related brain functions. [ABSTRACT FROM AUTHOR]

Dysfunction of the mesocorticolimbic dopamine system in medication overuse headache (MOH) is unknown. This study aimed to determine dopamine transporter (DAT) availability, which is sensitive to dopamine levels, in the mesocorticolimbic dopamine system in MOH patients. This case–control study investigated eligible MOH patients admitted to the International Headache Centre in the neurological department of Chinese PLA General Hospital between July 2018 and August 2019. All subjects underwent an integrated positron emission tomography (PET)/magnetic resonance (MR) brain scans with 11CFT, a radioligand that binds to DAT. Standardised uptake value ratio (SUVr) images were compared voxelwise between MOH patients and healthy controls (HCs). SUVr values from significantly changed regions were extracted, and partial correlation analyses with clinical measures were conducted. We examined 17 MOH patients and 16 HCs. MOH patients had lower SUVr levels in the medial rather than lateral orbitofrontal cortex (OFC) than HCs (T = −5.0317, PGRF < 0.01), which showed no correlation with clinical features. MOH is characterised by decreased DAT availability in the medial OFC, which might reflect compensatory downregulation due to low dopamine signalling within the mesocorticolimbic dopamine system and provide a new perspective to understand the pathogenesis of MOH. [ABSTRACT FROM AUTHOR]

Impaired social cognition is a core deficit in frontotemporal dementia (FTD). It is most commonly associated with the behavioural-variant of FTD, with atrophy of the orbitofrontal and ventromedial prefrontal cortex. Social cognitive changes are also common in semantic dementia, with atrophy centred on the anterior temporal lobes. The impairment of social behaviour in FTD has typically been attributed to damage to the orbitofrontal cortex and/or temporal poles and/or the uncinate fasciculus that connects them. However, the relative contributions of each region are unresolved. In this review, we present a unified neurocognitive model of controlled social behaviour that not only explains the observed impairment of social behaviours in FTD, but also assimilates both consistent and potentially contradictory findings from other patient groups, comparative neurology and normative cognitive neuroscience. We propose that impaired social behaviour results from damage to two cognitively- and anatomically-distinct components. The first component is social-semantic knowledge, a part of the general semantic-conceptual system supported by the anterior temporal lobes bilaterally. The second component is social control, supported by the orbitofrontal cortex, medial frontal cortex and ventrolateral frontal cortex, which interacts with social-semantic knowledge to guide and shape social behaviour. [ABSTRACT FROM AUTHOR]

Background: Obsessive-compulsive disorder (OCD) is characterized by persistent, unwanted thoughts and repetitive actions. Such repetitive thoughts and/or behaviors may be reinforced either by reducing anxiety or by avoiding a potential threat or harm, and thus may be rewarding to the individual. The possible involvement of the reward system in the symptomatology of OCD is supported by studies showing altered reward processing in reward-related regions, such as the ventral striatum (VS) and the orbitofrontal cortex (OFC), in adults with OCD. However, it is not clear whether this also applies to adolescents with OCD. Methods: Using functional magnetic resonance imaging, two sessions were conducted focusing on the anticipation and receipt of monetary reward (1) or loss (2), each contrasted to a verbal (control) condition. In each session, adolescents with OCD (n1=31/n2=26) were compared with typically developing (TD) controls (n1=33/ n2=31), all aged 10-19 years, during the anticipation and feedback phase of an adapted Monetary Incentive Delay task. Results: Data revealed a hyperactivation of the VS, but not the OFC, when anticipating both monetary reward and loss in the OCD compared to the TD group. Conclusions: These findings suggest that aberrant neural reward and loss processing in OCD is associated with greater motivation to gain or maintain a reward but not with the actual receipt. The greater degree of reward 'wanting' may contribute to adolescents with OCD repeating certain actions more and more frequently, which then become habits (i.e., OCD symptomatology). [ABSTRACT FROM AUTHOR]

Background: Transcranial magnetic stimulation (TMS) (including the theta burst stimulation (TBS) form of TMS used in this study) is a non-invasive means to stimulate nerve cells in superficial areas of the brain. In recent years, there has been a growth in the application of TMS to investigate the modulation of neural networks involved in substance use disorders. This study examines the feasibility of novel TMS protocols for the treatment of methamphetamine (MA) use disorder in an ambulatory drug and alcohol treatment setting. Methods: Thirty participants meeting the criteria for moderate to severe MA use disorder will be recruited in community drug and alcohol treatment settings and randomised to receive active TMS or sham (control) intervention. The treatment is intermittent TBS (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC), then continuous TBS (cTBS) to the left orbitofrontal cortex (OFC). Twelve sessions are administered over 4 weeks with opt-in weekly standardized cognitive behaviour therapy (CBT) counselling and a neuroimaging sub-study offered to participants. Primary outcomes are feasibility measures including recruitment, retention and acceptability of the intervention. Secondary outcomes include monitoring of safety and preliminary efficacy data including changes in substance use, cravings (cue reactivity) and cognition (response inhibition). Discussion: This study examines shorter TBS protocols of TMS for MA use disorder in real-world drug and alcohol outpatient settings where withdrawal and abstinence from MA, or other substances, are not eligibility requirements. TMS is a relatively affordable treatment and staff of ambulatory health settings can be trained to administer TMS. It is a potentially scalable and translatable treatment for existing drug and alcohol clinical settings. TMS has the potential to provide a much-needed adjuvant treatment to existing psychosocial interventions for MA use disorder. A limitation of this protocol is that the feasibility of follow-up is only examined at the end of treatment (4 weeks). Trial registration: Australia New Zealand Clinical Trial Registry ACTRN12622000762752. Registered on May 27, 2022, and retrospectively registered (first participant enrolled) on May 23, 2022, with protocol version 7 on February 24, 2023. [ABSTRACT FROM AUTHOR]

The neuronal cell adhesion molecule (NrCAM) is widely expressed and has important physiological functions in the nervous system across the lifespan, from axonal growth and guidance to spine and synaptic pruning, to organization of proteins at the nodes of Ranvier. NrCAM lies at the core of a functional protein network where multiple targets (including NrCAM itself) have been associated with schizophrenia. Here we investigated the effects of chronic unpredictable stress on latent inhibition, a measure of selective attention and learning which shows alterations in schizophrenia, in NrCAM knockout (KO) mice and their wild-type littermate controls (WT). Under baseline experimental conditions both NrCAM KO and WT mice expressed robust latent inhibition (p = 0.001). However, following chronic unpredictable stress, WT mice (p = 0.002), but not NrCAM KO mice (F < 1), expressed latent inhibition. Analyses of neuronal activation (c-Fos positive counts) in key brain regions relevant to latent inhibition indicated four types of effects: a single hit by genotype in IL cortex (p = 0.0001), a single hit by stress in Acb-shell (p = 0.031), a dual hit stress x genotype in mOFC (p = 0.008), vOFC (p = 0.020), and Acb-core (p = 0.032), and no effect in PrL cortex (p > 0.141). These results indicating a pattern of differential effects of genotype and stress support a complex stress × genotype interaction model and a role for NrCAM in stress-induced pathological behaviors relevant to schizophrenia and other psychiatric disorders. [ABSTRACT FROM AUTHOR]

The orbitofrontal cortex (OFC) is a key node in the cortico‐limbic‐striatal circuitry that influences decision‐making guided by the relative value of outcomes. Midbrain dopamine from either the ventral tegmental area (VTA) or the dorsal raphe nucleus (DRN) has the potential to modulate OFC neurons; however, it is unknown at what concentrations these terminals release dopamine. Male and female adult dopamine transporter (DAT)IRES‐Cre–tdTomato mice were injected with AAV2/8‐EF1a‐DIO‐eYFP into either the DRN or the VTA or the retrograde label cholera toxin B (CTB) 488 in the medial or lateral OFC. We quantified co‐expression of CTB 488 or enhanced yellow fluorescent protein (eYFP) with tdTomato fluorescence in VTA or DRN and eYFP fibre density in the medial or lateral OFC. Both VTA and DRN dopamine neurons project to either the medial OFC or the lateral OFC, with greater expression of fibres in the medial OFC. Using fast‐scan cyclic voltammetry, we detected optogenetically evoked dopamine from channelrhodopsin 2 (ChR2)‐expressing VTA or DRN dopamine terminals in either the medial OFC or the lateral OFC. We assessed if optical stimulation of dopamine from the VTA or the DRN onto the medial OFC could alter layer V pyramidal neuronal firing; however, we did not observe a change in firing at stimulation parameters that evoked dopamine release from either projection even though bath application of dopamine with the monoamine transporter inhibitor, nomifensine, decreased firing. In summary, dopaminergic neurons from the VTA or the DRN project to the OFC and release submicromolar dopamine in the medial and lateral OFC. [ABSTRACT FROM AUTHOR]

Rationale: Win-paired stimuli can promote risk taking in experimental gambling paradigms in both rats and humans. We previously demonstrated that atomoxetine, a noradrenaline reuptake inhibitor, and guanfacine, a selective α2A adrenergic receptor agonist, reduced risk taking on the cued rat gambling task (crGT), a rodent assay of risky choice in which wins are accompanied by salient cues. Both compounds also decreased impulsive premature responding. Objective: The key neural loci mediating these effects were unknown. The lateral orbitofrontal cortex (lOFC) and the medial prefrontal cortex (mPFC), which are highly implicated in risk assessment, action selection, and impulse control, receive dense noradrenergic innervation. We therefore infused atomoxetine and guanfacine directly into either the lOFC or prelimbic (PrL) mPFC prior to task performance. Results: When infused into the lOFC, atomoxetine improved decision making score and adaptive lose-shift behaviour in males, but not in females, without altering motor impulsivity. Conversely, intra-PrL atomoxetine improved impulse control in risk preferring animals of both sexes, but did not alter decision making. Guanfacine administered into the PrL, but not lOFC, also altered motor impulsivity in all subjects, though in the opposite direction to atomoxetine. Conclusions: These data highlight a double dissociation between the behavioural effects of noradrenergic signaling across frontal regions with respect to risky choice and impulsive action. Given that the influence of noradrenergic manipulations on motor impulsivity could depend on baseline risk preference, these data also suggest that the noradrenaline system may function differently in subjects that are susceptible to the risk-promoting lure of win-associated cues. [ABSTRACT FROM AUTHOR]

Animals, including humans, rely on contextual information to interpret ambiguous stimuli. Impaired context processing is a hallmark of several neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, post-traumatic stress disorder, and addiction. While sex differences in the prevalence and manifestations of these disorders are well established, potential sex differences in context processing remain uncertain. Here, we examined sex differences in the contextual control over cue-evoked reward seeking and its neural correlates, in rats. Male and female rats were trained in a bidirectional occasion-setting preparation in which the validity of two auditory reward-predictive cues was informed by the presence, or absence, of a visual contextual feature (LIGHT: X+/DARK: X−/LIGHT: Y−/DARK: Y+). Females were significantly slower to acquire contextual control over cue-evoked reward seeking. However, once established, the contextual control over behavior was more robust in female rats; it showed less within-session variability (less influence of prior reward) and greater resistance to acute stress. This superior contextual control achieved by females was accompanied by an increased activation of the orbitofrontal cortex (OFC) compared to males. Critically, these behavioral and neural sex differences were specific to the contextual modulation process and not observed in simple, context-independent, reward prediction tasks. These results indicate a sex-biased trade-off between the speed of acquisition and the robustness of performance in the contextual modulation of cued reward seeking. The different distribution of sexes along the fast learning ↔ steady performance continuum might reflect different levels of engagement of the OFC, and might have implications for our understanding of sex differences in psychiatric disorders.

BACKGROUND: Emotion-related impulsivity (ERI) refers to chronically poor self-control during periods of strong emotion. ERI robustly predicts psychiatric disorders and related problems, yet its neuroanatomical correlates are largely unknown. We tested whether local brain morphometry in targeted brain regions that integrate emotion and control could explain ERI severity. METHODS: One hundred twenty-two adults (ages 18-55 years) with internalizing or externalizing psychopathology completed a structural magnetic resonance imaging (MRI) scan, the Three-Factor Impulsivity Index, and the Structured Clinical Interview for DSM-5. The Three-Factor Impulsivity Index measures two types of ERI and a third type of impulsivity not linked to emotion. Cortical reconstruction yielded cortical thickness and local gyrification measurements. We evaluated whether morphometry in the orbitofrontal cortex (OFC), insula, amygdala, and nucleus accumbens was associated with ERI severity. Hypotheses and analyses were preregistered. RESULTS: Lower cortical gyrification in the right lateral OFC was associated with high ERI severity in a full, preregistered model. Separate examinations of local gyrification and cortical thickness also showed a positive association between gyrification in the left lateral OFC and ERI. An integrated measure of hemispheric imbalance in lateral OFC gyrification (right < left) correlated with ERI severity. These findings were specific to ERI and did not appear with non-emotion-related impulsivity. CONCLUSIONS: Local gyrification in the lateral OFC is associated with ERI severity. The current findings fit with existing theories of OFC function, strengthen the connections between the transdiagnostic literature in psychiatry and neuroscience, and may guide future treatment development.

Reward-seeking in the world is driven by cues that can have ambiguous predictive and motivational value. To produce adaptive, flexible reward-seeking, it is necessary to exploit occasion setters, other distinct features in the environment, to resolve the ambiguity of Pavlovian reward-paired cues. Despite this, very little research has investigated the neurobiological underpinnings of occasion setting, and as a result little is known about which brain regions are critical for occasion setting. To address this, we exploited a recently developed task that was amenable to neurobiological inquiry where a conditioned stimulus is only predictive of reward delivery if preceded in time by the non-overlapping presentation of a separate cue-an occasion setter. This task required male rats to maintain and link cue-triggered expectations across time to produce adaptive reward-seeking. We interrogated the contributions of the basolateral amygdala and orbitofrontal cortex to occasion setting as these regions are thought to be critical for the computation and exploitation of state value, respectively. Reversible inactivation of either structure prior to the occasion-setting task resulted in a profound inability of rats to use the occasion setter to guide reward-seeking. In contrast, inactivation of the dorsal hippocampus, a region fundamental for context-specific responding was without effect nor did inactivation of the basolateral amygdala or orbitofrontal cortex in a standard Pavlovian conditioning preparation affect conditioned responding. We conclude that neural activity within the orbitofrontal cortex and basolateral amygdala circuit is necessary to update and resolve ambiguity in the environment to promote cue-driven reward-seeking.

Anxious temperament, characterized by heightened behavioral and physiological reactivity to potential threat, is an early childhood risk factor for the later development of stress-related psychopathology. Using a well-validated nonhuman primate model, we tested the hypothesis that the prefrontal cortex (PFC) is critical in regulating the expression of primate anxiety-like behavior, as well as the function of subcortical components of the anxiety-related neural circuit. We performed aspiration lesions of a narrow strip of the posterior orbitofrontal cortex (OFC) intended to disrupt both cortex and axons entering, exiting and coursing through the pOFC, particularly those of the uncinate fasciculus (UF), a white matter tract that courses adjacent to and through this region. The OFC is of particular interest as a potential regulatory region because of its extensive reciprocal connections with amygdala, other subcortical structures and other frontal lobe regions. We validated this lesion method by demonstrating marked lesion-induced decreases in the microstructural integrity of the UF, which contains most of the fibers that connect the ventral PFC with temporal lobe structures as well as with other frontal regions. While the lesions resulted in modest decreases in threat-related behavior, they substantially decreased metabolism in components of the circuit underlying threat processing. These findings provide evidence for the importance of structural connectivity between the PFC and key subcortical structures in regulating the functions of brain regions known to be involved in the adaptive and maladaptive expression of anxiety.

Previous research suggests that excessive negative self-related thought during mind wandering involves the default mode network (DMN) core subsystem and the orbitofrontal cortex (OFC). Heart rate variability (HRV) biofeedback, which involves slow paced breathing to increase HRV, is known to promote emotional well-being. However, it remains unclear whether it has positive effects on mind wandering and associated brain function. We conducted a study where young adults were randomly assigned to one of two 5-week interventions involving daily biofeedback that either increased heart rate oscillations via slow paced breathing (Osc+ condition) or had little effect on heart rate oscillations (active control or Osc- condition). The two intervention conditions did not differentially affect mind wandering and DMN core-OFC functional connectivity. However, the magnitude of participants heart rate oscillations during daily biofeedback practice was associated with pre-to-post decreases in mind wandering and in DMN core-OFC functional connectivity. Furthermore, the reduction in the DMN core-OFC connectivity was associated with a decrease in mind wandering. Our results suggested that daily sessions involving high amplitude heart rate oscillations may help reduce negative mind wandering and associated brain function.

The ability to use information from ones prior actions is necessary for decision-making. While orbitofrontal cortex (OFC) has been hypothesized as key for inferences made using cue and value-related information, whether OFC populations contribute to the use of information from volitional actions to guide behavior is not clear. Here, we used a self-paced lever-press hold-down task in which mice infer prior lever-press durations to guide subsequent action performance. We show that the activity of genetically identified lateral OFC (lOFC) subpopulations differentially instantiate current and prior action information during ongoing action execution. Transient state-dependent lOFC circuit disruptions of specified subpopulations reduced the encoding of ongoing press durations but did not disrupt the use of prior action information to guide future action performance. In contrast, a chronic functional loss of lOFC circuit activity resulted in increased reliance on recently executed lever-press durations and impaired contingency reversal, suggesting the recruitment of compensatory mechanisms that resulted in repetitive action control. Our results identify a novel role for lOFC in the integration of action information to guide adaptive behavior.

Previous studies indicate that the structure and function of medial prefrontal cortex (PFC) and lateral orbitofrontal cortex (OFC) are associated with heart rate variability (HRV). Typically, this association is assumed to reflect the PFCs role in controlling HRV and emotion regulation, with better prefrontal structural integrity supporting greater HRV and better emotion regulation. However, as a control system, the PFC must monitor and respond to heart rate oscillatory activity. Thus, engaging in regulatory feedback during heart rate oscillatory activity may over time help shape PFC structure, as relevant circuits and connections are modified. In the current study with younger and older adults, we tested whether 5 weeks of daily sessions of biofeedback to increase heart rate oscillations (Osc+ condition) vs. to decrease heart rate oscillations (Osc- condition) affected cortical volume in left OFC and right OFC, two regions particularly associated with HRV in prior studies. The left OFC showed significant differences in volume change across conditions, with Osc+ increasing volume relative to Osc-. The volume changes in left OFC were significantly correlated with changes in mood disturbance. In addition, resting low frequency HRV increased more in the Osc+ than in the Osc- condition. These findings indicate that daily biofeedback sessions regulating heart rate oscillatory activity can shape both resting HRV and the brain circuits that help control HRV and regulate emotion.

We examined the safety and efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) of the right orbitofrontal cortex (OFC) in patients with refractory obsessive-compulsive disorder (OCD) and comorbid Major Depressive Disorder. All participants (n = 26) received excitatory stimulation of the left dorsolateral prefrontal cortex followed by inhibitory stimulation of bilateral supplementary motor area for 10 sessions. In 18 patients with poor early OCD response, treatment was augmented with OFC inhibitory stimulation after the tenth treatment session. Augmentation with OFC stimulation was well-tolerated, and associated with further alleviation of both OCD and depression symptoms, particularly in individuals with more severe illnesses.

We recorded directly from the orbital (oPFC) and ventromedial (vmPFC) subregions of the orbitofrontal cortex (OFC) in 22 (9 female, 13 male) epilepsy patients undergoing intracranial electroencephalography (iEEG) monitoring during an experimental task in which the participants judged the accuracy of self-referential autobiographical statements as well as valenced self-judgments (SJs). We found significantly increased high-frequency activity (HFA) in~13% of oPFC sites (10/18 subjects) and 16% of vmPFC sites (4/12 subjects) during both of these self-referential thought processes, with the HFA power being modulated by the content of selfreferential stimuli. The location of these activated sites corresponded with the location of fMRI-identified limbic network. Furthermore, the onset of HFA in the vmPFC was significantly earlier than that in the oPFC in all patients with simultaneous recordings in both regions. In 11 patients with available depression scores from comprehensive neuropsychological assessments, we documented diminished HFA in the OFC during positive SJ trials among individuals with higher depression scores; responses during negative SJ trials were not related to the patients' depression scores. Our findings provide new temporal and anatomical information about the mode of engagement in two important subregions of the OFC during autobiographical memory and SJ conditions. Our findings from the OFC support the hypothesis that diminished brain activity during positive self-evaluations, rather than heightened activity during negative self-evaluations, plays a key role in the pathophysiology of depression. [ABSTRACT FROM AUTHOR]

Patients with diffuse frontal gliomas often present with post‐operative apathy after tumour removal. However, the association between apathy and tumour removal of gliomas from the frontal lobe remains unknown. This study aimed to investigate the factors influencing post‐operative apathy after tumour removal in patients with diffuse frontal gliomas. We compared the demographics and clinical characteristics of patients with and without post‐operative apathy in a cohort of 54 patients who underwent awake brain mapping for frontal gliomas. The frequency of clinical parameters such as left‐sided involvement, high‐grade tumour types (WHO grades III, IV), main tumour location in the anterior cingulate gyrus (ACC) and/or dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) was significantly greater in the apathetic group compared to the non‐apathetic group. The apathetic group scored significantly lower on neuropsychological assessments such as the Letter Fluency Test among the Word Fluency Tests than the non‐pathetic group (p =.000). Moreover, the scores of Parts 3, and 3–1 of the Stroop test were significantly lower in the apathetic group than those in the non‐apathetic group (p =.023,.027, respectively). Multivariate model analysis revealed that the appearance of post‐operative apathy was significantly related to side of the of lesion [left vs. right, hazard ratio (HR) = 8.00, 95% confidence interval (CI) = 1.36–46.96, p =.021], location of the main tumour in the frontal lobe (ACC/DLPFC/OFC vs. others, HR = 7.99, 95% CI = 2.16–29.59, p =.002), and the Letter Fluency Test (HR =.37, 95% CI =.15–.90, p =.028). Post‐operative apathy is significantly associated with ACC and/or DLPFC and OFC in the left hemisphere of diffuse frontal gliomas. Apathy in frontal gliomas is correlated with a decline in the Letter Fluency Test scores. Therefore, this instrument is a potential predictor of post‐operative apathy in patients with diffuse frontal gliomas undergoing awake brain mapping. [ABSTRACT FROM AUTHOR]

The basolateral amygdala (BLA) and the nucleus accumbens core (NAcc) share some similar behavioral functions, such as associative learning, Pavlovian to instrumental transfer, and choice behavior. However, their prefrontal anatomical inputs have not been well characterized before, especially the collateral projections. In this study, we analyzed the distribution and collateralization of projections to the BLA and the NAcc from the prefrontal cortices (PFC), including the prelimbic (PL) and the infralimbic (IL) divisions of the medial prefrontal cortex (mPFC) and the subregions of the orbitofrontal cortex (OFC), such as the medial OFC (MO), the lateral OFC (LO), and the ventral OFC (VO). Double retrograde tracing approach was used, in which Cholera toxin subunit B conjugated with the Alexa Fluor 488 (CTB-AF488) or Alexa Fluor 594 (CTB-AF594) were unilaterally injected into the BLA and the NAcc, respectively, in male Long-Evans rats (n = 6). Among the sampled neurons, prefrontal projection to the BLA or the NAcc is more robust on the ipsilateral side, and more robust from the PL, the IL, and the MO compared to from the LO and the VO. The majority of the projections from the PFC to the BLA and/or the NAcc are confined in deep layer. In addition, for each of the prefrontal areas, about 15–25% BLA-projecting neurons send collateral projections to the NAcc, and vice versa. In conclusion, our data suggested that prefrontal control over the BLA and the NAcc is not entirely independent. The functional importance of the collateral projections awaits further examination. [ABSTRACT FROM AUTHOR]

Copyright of Religación: Revista de Ciencias Sociales y Humanidades is the property of Religacion: Revista de Ciencias Sociales y Humanidades and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Obesity has a profound impact on metabolic health thereby adversely affecting brain structure and function. However, the majority of previous studies used a single structural index to investigate the link between brain structure and body mass index (BMI), which hinders our understanding of structural covariance between regions in obesity. This study aimed to examine the relationship between macroscale cortical organization and BMI using novel morphometric similarity networks (MSNs). The individual MSNs were first constructed from individual eight multimodal cortical morphometric features between brain regions. Then the relationship between BMI and MSNs within the discovery sample of 434 participants was assessed. The key findings were further validated in an independent sample of 192 participants. We observed that the lateral non-reward orbitofrontal cortex (lOFC) exhibited decoupling (i.e., reduction in integration) in obesity, which was mainly manifested by its decoupling with the cognitive systems (i.e., DMN and FPN) while the medial reward orbitofrontal cortex (mOFC) showed de-differentiation (i.e., decrease in distinctiveness) in obesity, which was mainly represented by its de-differentiation with the cognitive and attention systems (i.e., DMN and VAN). Additionally, the lOFC showed de-differentiation with the visual system in obesity, while the mOFC showed decoupling with the visual system and hyper-coupling with the sensory-motor system in obesity. As an important first step in revealing the role of underlying structural covariance in body mass variability, the present study presents a novel mechanism that underlies the reward-control interaction imbalance in obesity, thus can inform future weight-management approaches.

Traumatic brain injury (TBI) is a leading cause of neurologic disability; the most common deficits affect prefrontal cortex-dependent functions such as attention, working memory, social behavior, and mental flexibility. Despite this prevalence, little is known about the pathophysiology that develops in frontal cortical microcircuits after TBI. We investigated whether alterations in subtype-specific inhibitory circuits are associated with cognitive inflexibility in a mouse model of frontal lobe contusion in both male and female mice that recapitulates aberrant mental flexibility as measured by deficits in rule reversal learning. Using patch-clamp recordings and optogenetic stimulation, we identified selective vulnerability in the non-fast-spiking and somatostatin-expressing (SOM+) subtypes of inhibitory neurons in layer V of the orbitofrontal cortex 2 months after injury. These subtypes exhibited reduced intrinsic excitability and a decrease in their synaptic output onto pyramidal neurons, respectively. By contrast, the fast-spiking and parvalbumin-expressing interneurons did not show changes in intrinsic excitability or synaptic output, respectively. Impairments in non-fast-spiking/SOM+ inhibitory circuit function were also associated with network hyperexcitability. These findings provide evidence for selective disruptions within specific inhibitory microcircuits that may guide the development of novel therapeutics for TBI.SIGNIFICANCE STATEMENT TBI frequently leads to chronic deficits in cognitive and behavioral functions that involve the prefrontal cortex, yet the maladaptive changes that occur in these cortical microcircuits are unknown. Our data indicate that alterations in subtype-specific inhibitory circuits, specifically vulnerability in the non-fast-spiking/somatostatin-expressing interneurons, occurs in the orbitofrontal cortex in the context of chronic deficits in reversal learning. These neurons exhibit reduced excitability and synaptic output, whereas the other prominent inhibitory population in layer V, the fast-spiking/parvalbumin-expressing interneurons as well as pyramidal neurons are not affected. Our work offers mechanistic insight into the subtype-specific function of neurons that may contribute to mental inflexibility after TBI.

We make complex decisions using both fast judgments and slower, more deliberative reasoning. For example, during value-based decision-making, animals make rapid value-guided orienting eye movements after stimulus presentation that bias the upcoming decision. The neural mechanisms underlying these processes remain unclear. To address this, we recorded from the caudate nucleus and orbitofrontal cortex while animals made value-guided decisions. Using population-level decoding, we found a rapid, phasic signal in caudate that predicted the choice response and closely aligned with animals' initial orienting eye movements. In contrast, the dynamics in orbitofrontal cortex were more consistent with a deliberative system serially representing the value of each available option. The phasic caudate value signal and the deliberative orbitofrontal value signal were largely independent from each other, consistent with value-guided orienting and value-guided decision-making being independent processes.

Abstract Background The negative emotional valence of a stimulus can be altered if paired with a pleasant stimulus, a phenomenon referred to as evaluative conditioning. Disgust, as a central emotion in obsessive-compulsive disorder (OCD), particularly in the contamination subtype, may be an appropriate target for such a method. We know that disgust processing and OCD pathophysiology share in some brain areas, including the orbitofrontal cortex, as the neuromodulation techniques targeted in this area have been able to decrease OCD symptoms. We aim to conduct a randomized clinical trial to investigate the evaluative conditioning effect on disgust reduction in patients with contamination-based OCD when administered with or without neuromodulation targeted orbitofrontal cortex. Method In a single-blind randomized control trial (RCT), 55 patients with contamination-based OCD will be randomly assigned to four arms. In a factorial design, they will receive 10 sessions of evaluative conditioning training (either sham or real) plus cathodal transcranial direct current stimulation (tDCS) over the orbitofrontal cortex (either sham or real). The intensity of disgust experience and clinical symptoms will be investigated as primary outcomes and quantitative electroencephalogram and cognitive functions as secondary outcomes. The data will be collected at three assessment levels: baseline, after completing intervention sessions, and 2-month follow-up. Discussion The present RCT is the first study that applies evaluative conditioning training in the OCD clinical sample. It will clarify the effect of the evaluative conditioning method alone and with tDCS on disgust reduction in patients with contamination-based OCD. It will provide initial evidence for such an emotion modulation method in the OCD population. The effect of this emotion-focused protocol on cognitive functions and electroencephalogram components is also of interest. Trial registration ClinicalTrials.gov, NCT05907369. Registered on 16 June 2023. Retrospectively registered.

Self-ambivalence, a prevalent phenomenon in daily life, has been increasingly substantiated by research. It refers to conflicting self-views and evaluations, primarily concerning self-worth and morality. Previous behavioral research has distinguished self-worth and moral ambivalence, but it remains unclear whether they have separable neural bases. The present study addressed this question by examining resting-state brain activity (i.e., the fractional amplitude of low-frequency fluctuations, fALFF) and connectivity (i.e., resting-state functional connectivity, RSFC) in 112 college students. The results found that self-worth ambivalence was positively related to the fALFF in the orbitofrontal cortex (OFC) and left superior parietal lobule (SPL). The RSFC strength between the SPL and precuneus/posterior cingulate cortex (PCC) was positively related to self-worth ambivalence. Moral ambivalence was positively associated with the fALFF in the left SPL (extending into the temporoparietal junction) and right SPL. The RSFC strengths between the left SPL/TPJ and OFC, as well as the RSFC strengths between the right SPL as a seed and the bilateral middle and inferior temporal gyrus, were associated with moral ambivalence. Overall, the neural bases of self-worth and moral ambivalence are associated with the SPL and OFC, involved in attentional alertness and value representation, respectively. Additionally, the neural basis of moral ambivalence is associated with the TPJ, responsible for mentalizing.

Endurance or aerobic exercise has many physical and mental health benefits, but less is known about the specific impact that cardiovascular activity may have on dopamine-associated brain circuits involved in reward processing and mood regulation in humans. Understanding such effects will help to explain individual differences in both exercise uptake and maintenance. This study evaluated neural response to a classical taste-conditioning reward prediction error task with the use of functional magnetic resonance imaging, along with data on self-reported aerobic exercise among healthy young adult females (N = 111). Results indicated positive associations between reported aerobic exercise and regional brain response that remained significant after multiple comparison correction for the right medial orbital frontal cortex response to unexpected sucrose receipt (r = 0.315, p = .0008). The medial orbitofrontal cortex is implicated in reward and outcome value computation and the results suggest that aerobic exercise may strengthen this circuitry, or reciprocally, higher orbitofrontal cortical activity may reinforce exercise behavior. The findings aid in developing a model of how exercise engagement can modify reward-circuit function and could be used therapeutically in conditions associated with altered brain salience response.

The chronic consumption of caloric dense high-fat foods is a major contributor to increased body weight, obesity, and other chronic health conditions. The orbitofrontal cortex (OFC) is critical in guiding decisions about food intake and is altered with diet-induced obesity. Obese rodents have altered morphologic and synaptic electrophysiological properties in the lateral orbitofrontal cortex (lOFC). Yet the time course by which exposure to a high-fat diet (HFD) induces these changes is poorly understood. Here, male mice are exposed to either short-term (7 d) or long-term (90 d) HFD. Long-term HFD exposure increases body weight, and glucose signaling compared with short-term HFD or a standard control diet (SCD). Both short and long-term HFD exposure increased the excitability of lOFC pyramidal neurons. However, phasic and tonic GABAergic signaling was differentially altered depending on HFD exposure length, such that tonic GABAergic signaling was decreased with early exposure to the HFD and phasic signaling was changed with long-term diet exposure. Furthermore, alterations in the short-term diet exposure were transient, as removal of the diet restored electrophysiological characteristics similar to mice fed SCD, whereas long-term HFD electrophysiological changes were persistent and remained after HFD removal. Finally, we demonstrate that changes in reward devaluation occur early with diet exposure. Together, these results suggest that the duration of HFD exposure differentially alters lOFC function and provides mechanistic insights into the susceptibility of the OFC to impairments in outcome devaluation. [ABSTRACT FROM AUTHOR]

The orbitofrontal cortex (OFC) is a functionally heterogeneous brain region contributing to mental processes relating to meditation practices. The OFC has been reported to decline in volume with increasing age and differs in volume between meditation practitioners and non-practitioners. We hypothesized that the age-related decline of the OFC is diminished in meditation practitioners. We tested this hypothesis in a sample of 50 long-term meditators and 50 matched controls by correlating chronological age with regional gray matter volumes of the left and right OFC, as well as in seven left and right cytoarchitectonically defined subregions of the OFC (Fo1–Fo7). In both meditators and controls, we observed a negative relationship between age and OFC (sub)volumes, indicating that older participants have smaller OFC volumes. However, in meditators, the age-related decline was less steep compared to controls. These age-related differences reached significance for left and right Fo2, Fo3, Fo4, and Fo7, as well as left Fo5 and right Fo6. Since different subregions of the OFC are associated with distinct brain functions, further investigations are required to explore the functional implications of these findings in the context of meditation and the aging brain. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with brain tumors often experience changes in memory and other aspects of thinking. Many may also have difficulty with social cognition, affecting the abilities that facilitate social behavior and maintain social relationships; however, the data are limited. Whether treatments such as cranial radiation can impact social cognition is not well-studied. We sought to understand how radiation dose exposure to the amygdala–orbitofrontal network, which subserves social cognition and emotion recognition, impacted performance on an emotion recognition task. We found that radiation dose to the amygdala and associated structures was associated with performance on an emotion recognition task, including longer response times with increasing radiation doses. Radiation techniques that reduce the dose to the amygdala-orbitofrontal network may decrease side effects for patients receiving cranial radiation. Background: Although data are limited, difficulty in social cognition occurs in up to 83% of patients with brain tumors. It is unknown whether cranial radiation therapy (RT) dose to the amygdala–orbitofrontal network can impact social cognition. Methods: We prospectively enrolled 51 patients with low-grade and benign brain tumors planned for cranial RT. We assessed longitudinal changes on an emotion recognition task (ERT) that measures the ability to recognize emotional states by displaying faces expressing six basic emotions and their association with the RT dose to the amygdala–orbitofrontal network. ERT outcomes included the median time to choose a response (ERTOMDRT) or correct response (ERTOMDCRT) and total correct responses (ERTHH). Results: The RT dose to the amygdala–orbitofrontal network was significantly associated with longer median response times on the ERT. Increases in median response times occurred at lower doses than decreases in total correct responses. The medial orbitofrontal cortex was the most important variable on regression trees predicting change in the ERTOMDCRT. Discussion: This is, to our knowledge, the first study to show that off-target RT dose to the amygdala–orbitofrontal network is associated with performance on a social cognition task, a facet of cognition that has previously not been mechanistically studied after cranial RT. [ABSTRACT FROM AUTHOR]

There is mounting evidence that COVID-19 infection is related to neuroinflammation, which has been associated with the development of neurodegenerative conditions such as Parkinson's and Alzheimer's Diseases. Holistic, mind–body tools and techniques commonly used in dance/movement therapy directly support neural mechanisms that may help prevent or slow this process. This article reviews recent biological research on the development and progress of COVID-19 and outlines an emerging connection between infection and the onset or progression of neurodegenerative illness, while indicating a role for dance/movement therapy in pandemic response and recovery. [ABSTRACT FROM AUTHOR]

Background: The negative emotional valence of a stimulus can be altered if paired with a pleasant stimulus, a phenomenon referred to as evaluative conditioning. Disgust, as a central emotion in obsessive-compulsive disorder (OCD), particularly in the contamination subtype, may be an appropriate target for such a method. We know that disgust processing and OCD pathophysiology share in some brain areas, including the orbitofrontal cortex, as the neuromodulation techniques targeted in this area have been able to decrease OCD symptoms. We aim to conduct a randomized clinical trial to investigate the evaluative conditioning effect on disgust reduction in patients with contamination-based OCD when administered with or without neuromodulation targeted orbitofrontal cortex. Method: In a single-blind randomized control trial (RCT), 55 patients with contamination-based OCD will be randomly assigned to four arms. In a factorial design, they will receive 10 sessions of evaluative conditioning training (either sham or real) plus cathodal transcranial direct current stimulation (tDCS) over the orbitofrontal cortex (either sham or real). The intensity of disgust experience and clinical symptoms will be investigated as primary outcomes and quantitative electroencephalogram and cognitive functions as secondary outcomes. The data will be collected at three assessment levels: baseline, after completing intervention sessions, and 2-month follow-up. Discussion: The present RCT is the first study that applies evaluative conditioning training in the OCD clinical sample. It will clarify the effect of the evaluative conditioning method alone and with tDCS on disgust reduction in patients with contamination-based OCD. It will provide initial evidence for such an emotion modulation method in the OCD population. The effect of this emotion-focused protocol on cognitive functions and electroencephalogram components is also of interest. Trial registration: ClinicalTrials.gov, NCT05907369. Registered on 16 June 2023. Retrospectively registered. [ABSTRACT FROM AUTHOR]

Alterations in resting-state functional connectivity (rsFC) of hippocampus and orbitofrontal cortex (OFC) have been highly implicated in major depressive disorder (MDD) and the researches have penetrated to the subregional level. However, relatively little is known about the intrinsic connectivity patterns of these two regions in adolescent MDD (aMDD), especially that of their functional subregions. Therefore, in the current study, we recruited 68 first-episode drug-naive aMDD patients and 43 matched typically developing controls (TDC) to characterize the alterations of whole-brain rsFC patterns in hippocampus and OFC at both regional and subregional levels in aMDD. The definition of specific functional subregions in hippocampus and OFC were based on the prior functional clustering-analysis results. Furthermore, the relationship between rsFC alterations and clinical features was also explored. Compared to TDC group, aMDD patients showed decreased connectivity of the left whole hippocampus with bilateral OFC and right inferior temporal gyrus at the regional level and increased connectivity between one of the right hippocampal subregions and right posterior insula at the subregional level. Reduced connectivity of OFC was only found in the subregion of left OFC with left anterior insula extending to lenticula in aMDD patients relative to TDC group. Our study identifies that the aberrant hippocampal and orbitofrontal rsFC was predominantly located in the insular cortex and could be summarized as an altered hippo-orbitofrontal-insular circuit in aMDD, which may be the unique features of brain network dysfunction in depression at this particular age stage. Moreover, we observed the distinct rsFC alterations in adolescent depression at the subregional level, especially the medial and lateral OFC. [ABSTRACT FROM AUTHOR]