Spontaneous slow wave oscillations in extracellular field potential recordings reflect the alternating dominance of excitation and inhibition.

In the resting state, cortical neurons can fire action potentials spontaneously but synchronously (Up state), followed by a quiescent period (Down state) before the cycle repeats. Extracellular recordings in the infragranular layer of cortex with a micro-electrode display a negative deflection (depth-negative) during Up states and a positive deflection (depth-positive) during Down states. The resulting slow wave oscillation (SWO) has been studied extensively during sleep and under anaesthesia. However, recent research on the balanced nature of synaptic excitation and inhibition has highlighted our limited understanding of its genesis. Specifically, are excitation and inhibition balanced during SWOs? We analyse spontaneous local field potentials (LFPs) during SWOs recorded from anaesthetised rats via a multi-channel laminar micro-electrode and show that the Down state consists of two distinct synaptic states: a Dynamic Down state associated with depth-positive LFPs and a prominent dipole in the extracellular field, and a Static Down state with negligible ( ≈ 0 mV $ \approx 0{\mathrm{\;mV}}$ ) LFPs and a lack of dipoles extracellularly. We demonstrate that depth-negative and -positive LFPs are generated by a shift in the balance of synaptic excitation and inhibition from excitation dominance (depth-negative) to inhibition dominance (depth-positive) in the infragranular layer neurons. Thus, although excitation and inhibition co-tune overall, differences in their timing lead to an alternation of dominance, manifesting as SWOs. We further show that Up state initiation is significantly faster if the preceding Down state is dynamic rather than static. Our findings provide a coherent picture of the dependence of SWOs on synaptic activity. KEY POINTS: Cortical neurons can exhibit repeated cycles of spontaneous activity interleaved with periods of relative silence, a phenomenon known as 'slow wave oscillation' (SWO). During SWOs, recordings of local field potentials (LFPs) in the neocortex show depth-negative deflection during the active period (Up state) and depth-positive deflection during the silent period (Down state). Here we further classified the Down state into a dynamic phase and a static phase based on a novel method of classification and revealed non-random, stereotypical sequences of the three states occurring with significantly different transitional kinetics. Our results suggest that the positive and negative deflections in the LFP reflect the shift of the instantaneous balance between excitatory and inhibitory synaptic activity of the local cortical neurons. The differences in transitional kinetics may imply distinct synaptic mechanisms for Up state initiation. The study may provide a new approach for investigating spontaneous brain rhythms.

Increased perivascular space volume in white matter and basal ganglia is associated with cognition in Parkinson's Disease.

Perivascular spaces (PVS), fluid-filled compartments surrounding brain vasculature, are an essential component of the glymphatic system responsible for transport of waste and nutrients. Glymphatic system impairment may underlie cognitive deficits in Parkinson's disease (PD). Studies have focused on the role of basal ganglia PVS with cognition in PD, but the role of white matter PVS is unknown. This study examined the relationship of white matter and basal ganglia PVS with domain-specific and global cognition in individuals with PD. Fifty individuals with PD underwent 3T T1w magnetic resonance imaging (MRI) to determine PVS volume fraction, defined as PVS volume normalized to total regional volume, within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of global cognitive function (Montreal Cognitive Assessment, and global cognitive composite score), and cognitive-specific domains (executive function, memory, visuospatial function, attention, and language). Higher white matter rostral middle frontal PVS was associated with lower scores in both global cognitive and visuospatial function. In the basal ganglia higher PVS was associated with lower scores for memory with a trend towards lower global cognitive composite score. While previous reports have shown that greater amount of PVS in the basal ganglia is associated with decline in global cognition in PD, our findings suggest that increased white matter PVS volume may also underlie changes in cognition.

Smoking, tobacco dependence, and neurometabolites in the dorsal anterior cingulate cortex.

Cigarette smoking has a major impact on global health and morbidity, and positron emission tomographic research has provided evidence for reduced inflammation in the human brain associated with cigarette smoking. Given the consequences of inflammatory dysfunction for health, the question of whether cigarette smoking affects neuroinflammation warrants further investigation. The goal of this project therefore was to validate and extend evidence of hypoinflammation related to smoking, and to examine the potential contribution of inflammation to clinical features of smoking. Using magnetic resonance spectroscopy, we measured levels of neurometabolites that are putative neuroinflammatory markers. N-acetyl compounds (N-acetylaspartate + N-acetylaspartylglutamate), glutamate, creatine, choline-compounds (phosphocholine + glycerophosphocholine), and myo-inositol, have all been linked to neuroinflammation, but they have not been examined as such with respect to smoking. We tested whether people who smoke cigarettes have brain levels of these metabolites consistent with decreased neuroinflammation, and whether clinical features of smoking are associated with levels of these metabolites. The dorsal anterior cingulate cortex was chosen as the region-of-interest because of previous evidence linking it to smoking and related states. Fifty-four adults who smoked daily maintained overnight smoking abstinence before testing and were compared with 37 nonsmoking participants. Among the smoking participants, we tested for associations of metabolite levels with tobacco dependence, smoking history, craving, and withdrawal. Levels of N-acetyl compounds and glutamate were higher, whereas levels of creatine and choline compounds were lower in the smoking group as compared with the nonsmoking group. In the smoking group, glutamate and creatine levels correlated negatively with tobacco dependence, and creatine correlated negatively with lifetime smoking, but none of the metabolite levels correlated with craving or withdrawal. The findings indicate a link between smoking and a hypoinflammatory state in the brain, specifically in the dorsal anterior cingulate cortex. Smoking may thereby increase vulnerability to infection and brain injury.

Surfactant-Dependent Bulk Scale Mechanochemical Synthesis of CsPbBr3 Nanocrystals for Plastic Scintillator-Based X-ray Imaging.

We report a facile, solvent-free surfactant-dependent mechanochemical synthesis of highly luminescent CsPbBr3 nanocrystals (NCs) and study their scintillation properties. A small amount of surfactant oleylamine (OAM) plays an important role in the two-step ball milling method to control the size and emission properties of the NCs. The solid-state synthesized perovskite NCs exhibit a high photoluminescence quantum yield (PLQY) of up to 88% with excellent stability. CsPbBr3 NCs capped with different amounts of surfactant were dispersed in toluene and mixed with polymethyl methacrylate (PMMA) polymer and cast into scintillator discs. With increasing concentration of OAM during synthesis, the PL yield of CsPbBr3/PMMA nanocomposite was increased, which is attributed to reduced NC aggregation and PL quenching. We also varied the perovskite loading concentration in the nanocomposite and studied the resulting emission properties. The most intense PL emission was observed from the 2% perovskite-loaded disc, while the 10% loaded disc exhibited the highest radioluminescence (RL) emission from 50 kV X-rays. The strong RL yield may be attributed to the deep penetration of X-rays into the composite, combined with the large interaction cross-section of the X-rays with the high-Z atoms within the NCs. The nanocomposite disc shows an intense RL emission peak centered at 536 nm and a fast RL decay time of 29.4 ns. Further, we have demonstrated the X-ray imaging performance of a 10% CsPbBr3 NC-loaded nanocomposite disc.

Alcohol Craving and Severity are Associated with Dorsal Anterior Cingulate Choline Levels in Individuals with an Alcohol Use Disorder.

AIMS: Magnetic resonance spectroscopy (MRS) has been used to probe inflammation in the brain. While altered MRS metabolite levels have previously been found in individuals with alcohol use disorder (AUD), the relationship between potential metabolite markers of inflammation and the clinical correlates of AUD remains understudied. Therefore, this exploratory study sought to elucidate the clinical significance of inflammation in AUD by examining relationships between metabolites, AUD severity, alcohol consumption, and craving in individuals with AUD. METHODS: Data for this secondary analysis are derived from a two-week clinical trial of ibudilast to treat AUD. Forty-three non-treatment-seeking individuals with an AUD (26M/17F) completed an MRS scan and alcohol-related questionnaires. MRS was performed using a multi-voxel array placed above the corpus callosum, extending from the pregnenual anterior cingulate to premotor cortex. The dorsal anterior cingulate was selected as the volume of interest. Metabolite levels of choline-compounds (Cho), myo-inositol (mI), and creatine+phosphocreatine (Cr) were quantified. Separate hierarchical regression models were used to evaluate the independent effects of metabolite levels on alcohol craving, alcohol problem severity, and alcohol consumption. RESULTS: Dorsal anterior cingulate Cho predicted alcohol craving and alcohol problem severity over and above demographics, medication, and alcohol consumption measures. mI and Cr did not predict alcohol craving or alcohol problem severity. Metabolite markers were not predictive of alcohol consumption. CONCLUSIONS: This preliminary study indicates that dACC Cho is sensitive to clinical characteristics of AUD. This is a further step in advancing neurometabolites, particularly Cho, as potential biomarkers and treatment targets for AUD.

Right Prefrontal Cortical Thickness Is Associated With Response to Cognitive-Behavioral Therapy in Children With Obsessive-Compulsive Disorder.

OBJECTIVE: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. METHOD: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. RESULTS: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. CONCLUSION: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.

Neurobiology of subtypes of trichotillomania and skin picking disorder.

BACKGROUND: Trichotillomania (TTM) and skin picking disorder (SPD) are common and often debilitating mental health conditions, grouped under the umbrella term of body-focused repetitive behaviors (BFRBs). Recent clinical subtyping found that there were three distinct subtypes of TTM and two of SPD. Whether these clinical subtypes map on to any unique neurobiological underpinnings, however, remains unknown. METHODS: Two hundred and fifty one adults [193 with a BFRB (85.5% [n = 165] female) and 58 healthy controls (77.6% [n = 45] female)] were recruited from the community for a multicenter between-group comparison using structural neuroimaging. Differences in whole brain structure were compared across the subtypes of BFRBs, controlling for age, sex, scanning site, and intracranial volume. RESULTS: When the subtypes of TTM were compared, low awareness hair pullers demonstrated increased cortical volume in the lateral occipital lobe relative to controls and sensory sensitive pullers. In addition, impulsive/perfectionist hair pullers showed relative decreased volume near the lingual gyrus of the inferior occipital-parietal lobe compared with controls. CONCLUSIONS: These data indicate that the anatomical substrates of particular forms of BFRBs are dissociable, which may have implications for understanding clinical presentations and treatment response.

Preliminary evidence for a lower brain age in children with attention-deficit/hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a debilitating disorder with apparent roots in abnormal brain development. Here, we quantified the level of individual brain maturation in children with ADHD using structural neuroimaging and a recently developed machine learning algorithm. More specifically, we compared the BrainAGE index between three groups matched for chronological age (mean ± SD: 11.86 ± 3.25 years): 89 children diagnosed with ADHD, 34 asymptomatic siblings of those children with ADHD, and 21 unrelated healthy control children. Brains of children with ADHD were estimated significantly younger (-0.85 years) than brains of healthy controls (Cohen's d = -0.33; p = 0.028, one-tailed), while there were no significant differences between unaffected siblings and healthy controls. In addition, more severe ADHD symptoms were significantly associated with younger appearing brains. Altogether, these results are in line with the proposed delay of individual brain maturation in children with ADHD. However, given the relatively small sample size (N = 144), the findings should be considered preliminary and need to be confirmed in future studies.

Clinical Characteristics of Youth with Trichotillomania (Hair-Pulling Disorder) and Excoriation (Skin-Picking) Disorder.

Body-focused repetitive disorders (BFRBDs) are understudied in youth and understanding of their underlying mechanisms is limited. This study evaluated BFRBD clinical characteristics, and two factors commonly implicated in their maintenance - emotion regulation and impulsivity - in 53 youth aged 11 to 17 years: 33 with BFRBDs and 20 controls. Evaluators administered psychiatric diagnostic interviews. Participants rated BFRBD severity, negative affect, quality of life, family functioning, emotion regulation, distress tolerance, and impulsivity. Youth with BFRBDs showed poorer distress tolerance and quality of life, and higher impulsivity and negative affect than controls, with no differences in family impairment. BFRBD distress/impairment, but not BFRBD severity, correlated with anxiety and depression, and poorer distress tolerance. Findings suggest youth with BFRBDs show clinical patterns aligning with prior research; highlight the role of distress tolerance in child BFRBDs; and suggest the utility of acceptance and mindfulness-based therapies for unpleasant emotions in BFRBDs. Continued research should evaluate factors underlying BFRBDs in youth.

Clinical MRI morphological analysis of functional seizures compared to seizure-naïve and psychiatric controls.

PURPOSE: Functional seizures (FS), also known as psychogenic nonepileptic seizures (PNES), are physical manifestations of acute or chronic psychological distress. Functional and structural neuroimaging have identified objective signs of this disorder. We evaluated whether magnetic resonance imaging (MRI) morphometry differed between patients with FS and clinically relevant comparison populations. METHODS: Quality-screened clinical-grade MRIs were acquired from 666 patients from 2006 to 2020. Morphometric features were quantified with FreeSurfer v6. Mixed-effects linear regression compared the volume, thickness, and surface area within 201 regions-of-interest for 90 patients with FS, compared to seizure-naïve patients with depression (n = 243), anxiety (n = 68), and obsessive-compulsive disorder (OCD, n = 41), respectively, and to other seizure-naïve controls with similar quality MRIs, accounting for the influence of multiple confounds including depression and anxiety based on chart review. These comparison populations were obtained through review of clinical records plus research studies obtained on similar scanners. RESULTS: After Bonferroni-Holm correction, patients with FS compared with seizure-naïve controls exhibited thinner bilateral superior temporal cortex (left 0.053 mm, p = 0.014; right 0.071 mm, p = 0.00006), thicker left lateral occipital cortex (0.052 mm, p = 0.0035), and greater left cerebellar white-matter volume (1085 mm3, p = 0.0065). These findings were not accounted for by lower MRI quality in patients with FS. CONCLUSIONS: These results reinforce prior indications of structural neuroimaging correlates of FS and, in particular, distinguish brain morphology in FS from that in depression, anxiety, and OCD. Future work may entail comparisons with other psychiatric disorders including bipolar and schizophrenia, as well as exploration of brain structural heterogeneity within FS.

Formamidinium Lead Halide Perovskite Nanocomposite Scintillators.

While there is great demand for effective, affordable radiation detectors in various applications, many commonly used scintillators have major drawbacks. Conventional inorganic scintillators have a fixed emission wavelength and require expensive, high-temperature synthesis; plastic scintillators, while fast, inexpensive, and robust, have low atomic numbers, limiting their X-ray stopping power. Formamidinium lead halide perovskite nanocrystals show promise as scintillators due to their high X-ray attenuation coefficient and bright luminescence. Here, we used a room-temperature, solution-growth method to produce mixed-halide FAPbX3 (X = Cl, Br) nanocrystals with emission wavelengths that can be varied between 403 and 531 nm via adjustments to the halide ratio. The substitution of bromine for increasing amounts of chlorine resulted in violet emission with faster lifetimes, while larger proportions of bromine resulted in green emission with increased luminescence intensity. By loading FAPbBr3 nanocrystals into a PVT-based plastic scintillator matrix, we produced 1 mm-thick nanocomposite scintillators, which have brighter luminescence than the PVT-based plastic scintillator alone. While nanocomposites such as these are often opaque due to optical scattering from aggregates of the nanoparticles, we used a surface modification technique to improve transmission through the composites. A composite of FAPbBr3 nanocrystals encapsulated in inert PMMA produced even stronger luminescence, with intensity 3.8× greater than a comparative FAPbBr3/plastic scintillator composite. However, the luminescence decay time of the FAPbBr3/PMMA composite was more than 3× slower than that of the FAPbBr3/plastic scintillator composite. We also demonstrate the potential of these lead halide perovskite nanocomposite scintillators for low-cost X-ray imaging applications.

Higher glutamatergic activity in the medial prefrontal cortex in chronic ketamine users.

BACKGROUND: The medial prefrontal cortex (mPFC) plays an important role in depression and addiction. Previous studies have shown alterations in glutamatergic activity in the mPFC following the administration of ketamine in patients with depression and healthy controls. However, it remains unclear whether chronic, nonmedical use of ketamine affects metabolites in the mPFC. METHODS: Using proton magnetic resonance spectroscopy, we measured metabolites (glutamate and glutamine [Glx]; phosphocreatine and creatine [PCr+Cr]; myo-inositol; N-acetyl-aspartate; and glycerophosphocholine and phosphocholine [GPC+PC]) in the mPFC of chronic ketamine users (n = 20) and healthy controls (n = 43). Among ketamine users, 60% consumed ketamine once per day or more, 10% consumed it every 2 days and 30% consumed it every 3 or more days. Using analysis of covariance, we evaluated between-group differences in the ratios of Glx:PCr+Cr, myo-inositol:PCr+Cr, N-acetyl-aspartate:PCr+Cr and GPC+PC:PCr+Cr. RESULTS: Chronic ketamine users showed significantly higher Glx:PCr+Cr ratios than healthy controls (median 1.05 v. 0.95, p = 0.008). We found no significant differences in myoinositol:PCr+Cr, N-acetyl-aspartate:PCr+Cr or GPC+PC:PCr+Cr ratios between the 2 groups. We found a positive relationship between N-acetyl-aspartate:PCr+Cr and Glx:PCr+Cr ratios in the healthy control group (R = 0.345, p = 0.023), but the ketamine use group failed to show such an association (ρ = 0.197, p = 0.40). LIMITATIONS: The cross-sectional design of this study did not permit causal inferences related to higher Glx:PCr+Cr ratios and chronic ketamine use. CONCLUSION: This study provides the first evidence that chronic ketamine users have higher glutamatergic activity in the mPFC than healthy controls; this finding may provide new insights relevant to the treatment of depression with ketamine.

Neurocircuit dynamics of arbitration between decision-making strategies across obsessive-compulsive and related disorders.

Obsessions and compulsions are central components of obsessive-compulsive disorder (OCD) and obsessive-compulsive related disorders such as body dysmorphic disorder (BDD). Compulsive behaviours may result from an imbalance of habitual and goal-directed decision-making strategies. The relationship between these symptoms and the neural circuitry underlying habitual and goal-directed decision-making, and the arbitration between these strategies, remains unknown. This study examined resting state effective connectivity between nodes of these systems in two cohorts with obsessions and compulsions, each compared with their own corresponding healthy controls: OCD (nOCD = 43; nhealthy = 24) and BDD (nBDD = 21; nhealthy = 16). In individuals with OCD, the left ventrolateral prefrontal cortex, a node of the arbitration system, exhibited more inhibitory causal influence over the left posterolateral putamen, a node of the habitual system, compared with controls. Inhibitory causal influence in this connection showed a trend for a similar pattern in individuals with BDD compared with controls. Those with stronger negative connectivity had lower obsession and compulsion severity in both those with OCD and those with BDD. These relationships were not evident within the habitual or goal-directed circuits, nor were they associated with depressive or anxious symptomatology. These results suggest that abnormalities in the arbitration system may represent a shared neural phenotype across these two related disorders that is specific to obsessive-compulsive symptoms. In addition to nosological implications, these results identify potential targets for novel, circuit-specific treatments.

Effects of ibudilast on central and peripheral markers of inflammation in alcohol use disorder: A randomized clinical trial.

Ibudilast, a neuroimmune modulator, shows promise as a pharmacotherapy for alcohol use disorder (AUD). In vivo administration of ibudilast reduces the expression of pro-inflammatory cytokines in animal models, but its effects on markers of inflammation in humans are unknown. This preliminary study examined the effect of ibudilast on peripheral and potential central markers of inflammation in individuals with AUD. This study also explored the predictive relationship of neurometabolite markers with subsequent drinking in the trial. Non-treatment-seeking individuals with an AUD (n = 52) were randomized to receive oral ibudilast (n = 24) or placebo (n = 28) for 2 weeks. Plasma levels of peripheral inflammatory markers were measured at baseline and after 1 and 2 weeks of medication. At study mid-point, proton magnetic resonance spectroscopy was performed to measure potential neurometabolite markers of inflammation: choline-compounds (Cho), myo-inositol (MI) and creatine + phosphocreatine (Cr) in frontal and cingulate cortices from 43 participants (ibudilast: n = 20; placebo: n = 23). The treatment groups were compared on peripheral and central markers. Ibudilast-treated participants had lower Cho in superior frontal white matter and nominally lower MI in pregenual anterior cingulate cortex. Ibudilast-treated participants had nominally lower C-reactive protein levels at visit 2 and nominally lower TNF-α/IL-10 ratios, relative to placebo. C-reactive protein and Cho levels were correlated, controlling for medication. Superior frontal white matter Cho predicted drinking in the following week. Micro-longitudinal ibudilast treatment may induce peripheral and putative central anti-inflammatory responses in patients with AUD. The neurometabolite responses may be associated with reduction in drinking, suggesting an anti-inflammatory component to the therapeutic action of ibudilast.

Magnetic resonance spectroscopy shows associations between neurometabolite levels and perivascular space volume in Parkinson's disease: a pilot and feasibility study.

OBJECTIVE: Higher volume fraction of perivascular space (PVS) has recently been reported in Parkinson's disease (PD) and related disorders. Both elevated PVS and altered levels of neurometabolites, assayed by proton magnetic resonance spectroscopy (MRS), are suspected indicators of neuroinflammation, but no published reports have concurrently examined PVS and MRS neurometabolites. METHODS: In an exploratory pilot study, we acquired multivoxel 3-T MRS using a semi-Localization by Adiabatic SElective Refocusing (sLASER) pulse-sequence (repetition time/echo time = 2810/60 ms, voxels 10 × 10 × 10 mm3) from a 2D slab sampling bilateral frontal white matter (FWM) and anterior middle cingulate cortex (aMCC). PVS maps obtained from high-resolution (0.8 × 0.8 × 0.8 mm3) T1-weighted MRI were co-registered with MRS. In each MRS voxel, PVS volume and neurometabolite levels were measured. RESULTS: Linear regression accounting for age, sex, and BMI found greater PVS volume for higher levels of choline-containing compounds (Cho; P = 0.047) in FWM and lower PVS volume for higher levels of N-acetyl compounds (NAA; P = 0.012) in aMCC. Since (putatively) higher Cho is associated with inflammation while NAA has anti-inflammatory properties, these observations add to evidence that higher PVS load is a sign of inflammation. Additionally, lower Montreal Cognitive Assessment scores were associated with lower NAA in aMCC (P = 0.002), suggesting that local neuronal dysfunction and inflammation contribute to cognitive impairment in PD. CONCLUSION: These exploratory findings indicate that co-analysis of PVS and MRS is feasible and may help elucidate the cellular and metabolic substrates of glymphatic and inflammatory processes in PD.

Metabolite differences in the medial prefrontal cortex in schizophrenia patients with and without persistent auditory verbal hallucinations: a 1H MRS study.

Studies of schizophrenia (SCZ) have associated auditory verbal hallucinations (AVH) with structural and functional abnormalities in frontal cortex, especially medial prefrontal cortex (mPFC). Although abnormal prefrontal network connectivity associated with language production has been studied extensively, the relationship between mPFC dysfunction (highly relevant to the pathophysiology of SCZ) and AVH has been rarely investigated. In this study, proton magnetic resonance spectroscopy was used to measure metabolite levels in the mPFC in 61 SCZ patients with persistent AVH (pAVH), 53 SCZ patients without AVH (non-AVH), and 59 healthy controls (HC). The pAVH group showed significantly lower levels of N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (tNAA) and glutamate + glutamine (Glx), compared with the non-AVH (tNAA: p = 0.022, Glx: p = 0.012) and HC (tNAA: p = 0.001, Glx: p = 0.001) groups. No difference was found in the levels of tNAA and Glx between non-AVH and HC. The levels of tNAA and Glx in the mPFC was negatively correlated with the severity of pAVH (tNAA: r = -0.24, p = 0.014; Glx: r = -0.30, p = 0.002). In conclusion, pAVH in SCZ patients might be related to decreased levels of tNAA and Glx in the mPFC, indicating that tNAA or Glx might play a key role in the pathogenesis of pAVH.

The Mental Maxwell Relations: A Thermodynamic Allegory for Higher Brain Functions.

The theoretical framework of classical thermodynamics unifies vastly diverse natural phenomena and captures once-elusive effects in concrete terms. Neuroscience confronts equally varied, equally ineffable phenomena in the mental realm, but has yet to unite or to apprehend them rigorously, perhaps due to an insufficient theoretical framework. The terms for mental phenomena, the mental variables, typically used in neuroscience are overly numerous and imprecise. Unlike in thermodynamics or other branches of physics, in neuroscience, there are no core mental variables from which all others formally derive and it is unclear which variables are distinct and which overlap. This may be due to the nature of mental variables themselves. Unlike the variables of physics, perhaps they cannot be interpreted as composites of a small number of axioms. However, it is well worth exploring if they can, as that would allow more parsimonious theories of higher brain function. Here we offer a theoretical exercise in the spirit of the National Institutes of Health Research Domain Criteria (NIH RDoC) Initiative and the Cognitive Atlas Project, which aim to remedy this state of affairs. Imitating classical thermodynamics, we construct a formal framework for mental variables, an extended analogy - an allegory - between mental and thermodynamic quantities. Starting with mental correlates of the physical indefinables length, time, mass or force, and charge, we pursue the allegory up to mental versions of the thermodynamic Maxwell Relations. The Maxwell Relations interrelate the thermodynamic quantities volume, pressure, temperature, and entropy and were chosen since they are easy to derive, yet capable of generating nontrivial, nonobvious predictions. Our "Mental Maxwell Relations" interlink the mental variables consciousness, salience, arousal, and distraction and make nontrivial, nonobvious statements about mental phenomena. The mental system thus constructed is internally consistent, in harmony with introspection, and respects the RDoC criteria of employing only psychologically valid constructs with some evidence of a brain basis. We briefly apply these concepts to the problem of decision-making and sketch how some of them might be tested empirically.

Neural basis of associative learning in Trichotillomania and skin-picking disorder.

Disorders such as Trichotillomania (TTM) and skin-picking disorder (SPD) are associated with reduced flexibility and increased internally focused attention. While the basal ganglia have been hypothesized to play a key role, the mechanisms underlying learning and flexible accommodation of new information is unclear. Using a Bayesian Learning Model, we evaluated the neural basis of learning and accommodation in individuals with TTM and/or SPD. Participants were 127 individuals with TTM and/or SPD (TTM/SPD) recruited from three sites (age 18-57, 84% female) and 26 healthy controls (HC). During fMRI, participants completed a shape-button associative learning and reversal fMRI task. Above-threshold clusters were identified where the Initial Learning-Reversals BOLD activation contrast differed significantly (p < .05 FDR-corrected) between the two groups. A priori, effects were anticipated in predefined ROIs in bilateral basal ganglia, with exploratory analyses in the hippocampus, dorsolateral prefrontal cortex (dlPFC), and dorsal anterior cingulate cortex (dACC). Relative to HC, individuals with TTM/SPD demonstrated reduced activation during initial learning compared to reversal learning in the right basal ganglia. Similarly, individuals with TTM/SPD demonstrated reduced activation during initial learning compared to reversal learning in several clusters in the dlPFC and dACC compared to HC. Individuals with TTM/SPD may form or reform visual stimulus-motor response associations through different brain mechanisms than healthy controls. The former exhibit altered activation within the basal ganglia, dlPFC, and dACC during an associative learning task compared to controls, reflecting reduced frontal-subcortical activation during initial learning. Future work should determine whether these neural deficits may be restored with targeted treatment.

An overview of the first 5 years of the ENIGMA obsessive-compulsive disorder working group: The power of worldwide collaboration.

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive-compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.

Reward processing in trichotillomania and skin picking disorder.

Trichotillomania (hair pulling disorder) and skin picking disorder are common and often debilitating mental health conditions, grouped under the umbrella term of body focused repetitive behaviors (BFRBs). Although the pathophysiology of BFRBs is incompletely understood, reward processing dysfunction has been implicated in the etiology and sustention of these disorders. The purpose of this study was to probe reward processing in BFRBs. 159 adults (125 with a BFRB [83.2% (n = 104) female] and 34 healthy controls [73.5% (n = 25) female]) were recruited from the community for a multi-center between-group comparison using a functional imaging (fMRI) monetary reward task. Differences in brain activation during reward anticipation and punishment anticipation were compared between BFRB patients and controls, with stringent correction for multiple comparisons. All group level analyses controlled for age, sex and scanning site. Compared to controls, BFRB participants showed marked hyperactivation of the bilateral inferior frontal gyrus (pars opercularis and pars triangularis) compared to controls. In addition, BFRB participants exhibited increased activation in multiple areas during the anticipation of loss (right fusiform gyrus, parahippocampal gyrus, cerebellum, right inferior parietal lobule; left inferior frontal gyrus). There were no significant differences in the win-lose contrast between the two groups. These data indicate the existence of dysregulated reward circuitry in BFRBs. The identified pathophysiology of reward dysfunction may be useful to tailor future treatments.