Brain age of rhesus macaques over the lifespan.

Through the application of machine learning algorithms to neuroimaging data the brain age methodology was shown to provide a useful individual-level biological age prediction and identify key brain regions responsible for the prediction. In this study, we present the methodology of constructing a rhesus macaque brain age model using a machine learning algorithm and discuss the key predictive brain regions in comparison to the human brain, to shed light on cross-species primate similarities and differences. Structural information of the brain (e.g., parcellated volumes) from brain magnetic resonance imaging of 43 rhesus macaques were used to develop brain atlas-based features to build a brain age model that predicts biological age. The best-performing model used 22 selected features and achieved an R2 of 0.72. We also identified interpretable predictive brain features including Right Fronto-orbital Cortex, Right Frontal Pole, Right Inferior Lateral Parietal Cortex, and Bilateral Posterior Central Operculum. Our findings provide converging evidence of the parallel and comparable brain regions responsible for both non-human primates and human biological age prediction.

Left Ventricular Myocardial Work Improves in Response to Treatment and is Associated with Survival Among Patients with Light-Chain Cardiac Amyloidosis.

AIMS: Complete hematologic response to treatment for light chain cardiac amyloidosis (AL-CA) may lead to improvement of myocardial function and better outcomes. We sought to evaluate the effect of response to treatment for AL-CA on echocardiographic indices of myocardial deformation and work, and their prognostic significance. METHODS AND RESULTS: Sixty-one patients treated for AL were enrolled and underwent echocardiographic assessment at baseline and at 1-year. Patients were stratified according to hematologic response as complete or not complete responders. A significant reduction in median NT-proBNP (2,771 to 1,486 pg/mL; p < 0.001), posterior wall thickness (PWT) (13 to 12 mm; p = 0.002), and an increase in global work index (GWI) (1,115 to 1,356 mmHg%; p = 0.018) was observed at 1-year. Patients with complete response (CR) had a more pronounced decrease in intraventricular septum thickness (14.2 to 12.0 mm; p = 0.006), improved global longitudinal strain (GLS) (-11.6 to -13.1%; p for interaction = 0.045), increased global constructive work (1,245 to 1,436 mmHg%; p = 0.008) and global work index (926 to 1250 mmHg%, p = 0.002) compared to non-CR. Furthermore, deltaGLS (ρspearman = 0.35; p < 0.001) and deltaGWI (ρspearman = -0.32; p = 0.02) correlated with delta NT-proBNP. Importantly, patients with GLS and GWI response had a better prognosis (log-rank p = 0.048 and log-rank p = 0.007, respectively). After adjustment for Mayo stage, gender, and response status, deltaGLS (HR = 1.404, p = 0.046 per 1% increase) and deltaGWI (HR = 0.996, p = 0.042 per 1mmHg% increase) were independent predictors of survival. CONCLUSIONS: Complete hematologic response to treatment is associated with improved left ventricular myocardial work indices and their change is associated with improved survival in AL-CA.

Individual Differences on Wellbeing Indices during the COVID-19 Quarantine in Greece: A National Study.

The impact of COVID-19 and the associated lockdown measures on people's physical and mental wellbeing, as well as their daily lives and functioning, has been extensively studied. This study takes the approach of investigating the consequences of COVID-19 on a national scale, considering sociodemographic factors. The main objective is to make a contribution to ongoing research by specifically examining how age, gender, and marital status influence the overall impact of COVID-19 and wellbeing indicators during the second lockdown period that was implemented in response to the COVID-19 pandemic in the Greek population. The study involved a sample of 16,906 individuals of all age groups in Greece who completed an online questionnaire encompassing measurements related to personal wellbeing, the presence and search for meaning in life, positive relationships, as well as symptoms of depression, anxiety, and stress. Additionally, to gauge the levels of the perceived COVID-19-related impact, a valid and reliable scale was developed. The results reveal that a higher perception of COVID-19 consequences is positively associated with psychological symptoms and the search for meaning in life, while being negatively correlated with personal wellbeing and the sense of meaning in life. In terms of individual differences, the findings indicate that unmarried individuals, young adults, and females tend to report higher levels of psychological symptoms, a greater search for meaning in life, and a heightened perception of COVID-19-related impact. These findings are analyzed in depth, and suggestions for potential directions for future research are put forth.

Radiologic findings of osteonecrosis, osteoradionecrosis, osteomyelitis and jaw metastatic disease with cone beam CT.

PURPOSE: The purpose of this study was to assess CBCT scans of patients with medication related osteonecrosis of the jaws (MRONJ), osteoradionecrosis (ORN), osteomyelitis (OM) and jaw metastatic disease (JM), evaluate the presence and extent of radiologic findings, identify radiologic parameters that may distinguish the four entities and last, introduce a new modified radiographic index (CRIm), in order to contribute to the diagnosis of these conditions. METHODS: Τwo major databases were retrospectively searched for fully documented and diagnosed CBCT scans of MRONJ, ORN, OM and JM from 2006 to 2019. 335 CBCT scans met the inclusion criteria and were assessed under standardized viewing conditions blindly by 2 observers. The CRIm index proposed in this study evaluates: lytic changes, sclerosis, periosteal bone formation, sequestration, non-healing extraction sockets and other findings which included: sinus implication, inferior alveolar canal implication and jaw fracture. Lytic changes, sclerosis, periosteal bone formation, sequestration and non-healing extraction sockets were scored as: absent (0), localized/single (1) and extensive/multiple (2). Each one of other findings were scored individually as: absent (0) and present (1). For statistical analysis t-test, Pearson's r correlation coefficient, one-way ANOVA and Bonferonni were performed. RESULTS: Extensive lytic changes were the most common finding, especially for ORN, where it occurred in all CBCT scans (100%). The mean value of the CRIm index differs significantly between CBCT scans with MRONJ and JM, as well as between those with OM and JM (Bonferroni p < 0.001). CONCLUSIONS: The new modified Composite Radiographic Index introduced in this study, appears to have improved an objective approach to the previously used Composite Radiographic Index by means of cumulative radiologic features. Τhe predominance of certain radiologic features in one or more of these entities may lead the diagnostician towards the correct diagnosis.

Cardiovascular Toxicity of Proteasome Inhibitors: Underlying Mechanisms and Management Strategies: JACC: CardioOncology State-of-the-Art Review.

Proteasome inhibitors (PIs) are the backbone of combination treatments for patients with multiple myeloma and AL amyloidosis, while also indicated in Waldenström's macroglobulinemia and other malignancies. PIs act on proteasome peptidases, causing proteome instability due to accumulating aggregated, unfolded, and/or damaged polypeptides; sustained proteome instability then induces cell cycle arrest and/or apoptosis. Carfilzomib, an intravenous irreversible PI, exhibits a more severe cardiovascular toxicity profile as compared with the orally administered ixazomib or intravenous reversible PI such as bortezomib. Cardiovascular toxicity includes heart failure, hypertension, arrhythmias, and acute coronary syndromes. Because PIs are critical components of the treatment of hematological malignancies and amyloidosis, managing their cardiovascular toxicity involves identifying patients at risk, diagnosing toxicity early at the preclinical level, and offering cardioprotection if needed. Future research is required to elucidate underlying mechanisms, improve risk stratification, define the optimal management strategy, and develop new PIs with safe cardiovascular profiles.

Cognitive and personality predictors of school performance from preschool to secondary school: An overarching model.

In this article, existing research investigating how school performance relates to cognitive, self-awareness, language, and personality processes is reviewed. We outline the architecture of the mind, involving a general factor, g, that underlies distinct mental processes (i.e., executive, reasoning, language, cognizance, and personality processes). From preschool to adolescence, g shifts from executive to reasoning and cognizance processes; personality also changes, consolidating in adolescence. There are three major trends in the existing literature: (a) All processes are highly predictive of school achievement if measured alone, each accounting for ∼20% of its variance; (b) when measured together, cognitive processes (executive functions and representational awareness in preschool and fluid intelligence after late primary school) dominate as predictors (over ∼50%), drastically absorbing self-concepts and personality dispositions that drop to ∼3%-5%; and (c) predictive power changes according to the processes forming g at successive levels: attention control and representational awareness in preschool (∼85%); fluid intelligence, language, and working memory in primary school (∼53%); fluid intelligence, language, self-evaluation, and school-specific self-concepts in secondary school (∼70%). Stability and plasticity of personality emerge as predictors in secondary school. A theory of educational priorities is proposed, arguing that (a) executive and awareness processes; (b) information management; and (c) reasoning, self-evaluation, and flexibility in knowledge building must dominate in preschool, primary, and secondary school, respectively. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cardiac mechanics in response to proteasome inhibition: a prospective study.

AIM: Ubiquitin-Proteasome System (UPS) is of paramount importance regarding the function of the myocardial cell. Consistently, inhibition of this system has been found to affect myocardium in experimental models; yet, the clinical impact of UPS inhibition on cardiac function has not been comprehensively examined. Our aim was to gain insight into the effect of proteasome inhibition on myocardial mechanics in humans. METHODS AND RESULTS: We prospectively evaluated 48 patients with multiple myeloma and an indication to receive carfilzomib, an irreversible proteasome inhibitor. All patients were initially evaluated and underwent echocardiography with speckle tracking analysis. Carfilzomib was administered according to Kd treatment protocol. Follow-up echocardiography was performed at the 3rd and 6th month. Proteasome activity (PrA) was measured in peripheral blood mononuclear cells.At 3 months after treatment, we observed early left ventricular (LV) segmental dysfunction and deterioration of left atrial (LA) remodelling, which was sustained and more pronounced than that observed in a cardiotoxicity control group. At 6 months, LV and right ventricular functions were additionally attenuated (P < 0.05 for all). These changes were independent of blood pressure, endothelial function, inflammation, and cardiac injury levels. Changes in PrA were associated with changes in global longitudinal strain (GLS), segmental LV strain, and LA markers (P < 0.05 for all). Finally, baseline GLS < -18% or LA strain rate > 1.71 were associated with null hypertension events. CONCLUSION: Inhibition of the UPS induced global deterioration of cardiac function.

Changing priorities in the development of cognitive competence and school learning: A general theory.

This paper summarizes a theory of cognitive development and elaborates on its educational implications. The theory postulates that development occurs in cycles along multiple fronts. Cognitive competence in each cycle comprises a different profile of executive, inferential, and awareness processes, reflecting changes in developmental priorities in each cycle. Changes reflect varying needs in representing, understanding, and interacting with the world. Interaction control dominates episodic representation in infancy; attention control and perceptual awareness dominate in realistic representations in preschool; inferential control and awareness dominate rule-based representation in primary school; truth and validity control and precise self-evaluation dominate in principle-based thought in adolescence. We demonstrate that the best predictors of school learning in each cycle are the cycle's cognitive priorities. Also learning in different domains, e.g., language and mathematics, depends on an interaction between the general cognitive processes dominating in each cycle and the state of the representational systems associated with each domain. When a representational system is deficient, specific learning difficulties may emerge, e.g., dyslexia and dyscalculia. We also discuss the educational implications for evaluation and learning at school.

Patient-specific connectomic models correlate with, but do not reliably predict, outcomes in deep brain stimulation for obsessive-compulsive disorder.

Deep brain stimulation (DBS) of the ventral internal capsule/ventral striatum (VCVS) is an emerging treatment for obsessive-compulsive disorder (OCD). Recently, multiple studies using normative connectomes have correlated DBS outcomes to stimulation of specific white matter tracts. Those studies did not test whether these correlations are clinically predictive, and did not apply cross-validation approaches that are necessary for biomarker development. Further, they did not account for the possibility of systematic differences between DBS patients and the non-diagnosed controls used in normative connectomes. To address these gaps, we performed patient-specific diffusion imaging in 8 patients who underwent VCVS DBS for OCD. We delineated tracts connecting thalamus and subthalamic nucleus (STN) to prefrontal cortex via VCVS. We then calculated which tracts were likely activated by individual patients' DBS settings. We fit multiple statistical models to predict both OCD and depression outcomes from tract activation. We further attempted to predict hypomania, a VCVS DBS complication. We assessed all models' performance on held-out test sets. With this best-practices approach, no model predicted OCD response, depression response, or hypomania above chance. Coefficient inspection partly supported prior reports, in that capture of tracts projecting to cingulate cortex was associated with both YBOCS and MADRS response. In contrast to prior reports, however, tracts connected to STN were not reliably correlated with response. Thus, patient-specific imaging and a guideline-adherent analysis were unable to identify a tractographic target with sufficient effect size to drive clinical decision-making or predict individual outcomes. These findings suggest caution in interpreting the results of normative connectome studies.

Daratumumab May Attenuate Cardiac Dysfunction Related to Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma: A Prospective Study.

Carfilzomib has improved survival in patients with relapsed/refractory multiple myeloma (RRMM), but it may exert cardiovascular adverse events (CVAEs). The aim of this study was to assess whether treatment with daratumumab may ameliorate carfilzomib-related toxicity. We prospectively evaluated 25 patients with RRMM who received either daratumumab in combination with carfilzomib and dexamethasone (DaraKd) (n = 14) or Kd (n = 11). Cardiac ultrasound was performed before treatment initiation and C6D16 or at the time of treatment interruption. Patients were followed for a median of 10 months for CVAEs. The mean (± SD) age was 67.8 ± 7.6 years and 60% were men. The two treatment groups did not significantly differ in baseline demographic characteristics (p > 0.1 for all). In the DaraKd group, we did not observe any significant change in markers of ventricular systolic function. However, these markers deteriorated in the Kd group; left ventricular (LV) ejection fraction, LV global longitudinal strain, tricuspid annular plane systolic excursion and RV free wall longitudinal strain significantly decreased from baseline to second visit (p < 0.05). A significant group interaction (p < 0.05) was observed for the abovementioned changes. CVAEs occurred more frequently in the Kd than the DaraKd group (45% vs. 28.6%). DaraKd was associated with preserved post-treatment cardiac systolic function and lower CVAE rate compared with Kd. The clinical significance and the underlying mechanisms merit further investigation.

A Research Domain Criteria Approach to Gambling Disorder and Behavioral Addictions: Decision-Making, Response Inhibition, and the Role of Cannabidiol.

Gambling Disorder (GD) has been recently re-classified in the DSM-5 under the "substance-related and addictive disorders," in light of its genetic, endophenotypic, and phenotypic resemblances to substance dependence. Diminished control is a core defining concept of psychoactive substance dependence or addiction and has given rise to the concept of "behavioral" addictions, which are syndromes analogous to substance addiction, but with a behavioral focus other than ingestion of a psychoactive substance. The main symptom clusters are represented by loss of control, craving/withdrawal, and neglect of other areas of life, whereas in a Research Domain Criteria (RDoC) perspective, GD patients exhibit deficits in the domain of "Positive valence systems," particularly in the "Approach motivation" and "Reward learning" constructs, as well as in the "Cognitive systems," primarily in the "Cognitive control" construct. In the Addictions Neuroclinical Assessment (ANA), three relevant domains for addictions emerge: "Incentive salience," "Negative Emotionality," and "Executive Function." The endocannabinoid system (ECS) may largely modulate these circuits, presenting a promising pharmaceutical avenue for treating addictions. Up to now, research on cannabidiol has shown some efficacy in Attention Deficit/Hyperactivity Disorder (ADHD), whereas in behavioral addictions its role has not been fully elucidated, as well as its precise action on RDoC domains. Herein, we review available evidence on RDoC domains affected in GD and behavioral addictions and summarize insights on the use of cannabidiol in those disorders and its potential mechanisms of action on reward, decisional, and sensorimotor processes.

Clinical validation of time reduction strategy in continuous step-and-shoot mode during SPECT acquisition.

BACKGROUND: The SwiftScan solution (General Electric Healthcare) combines a new low-energy high-resolution sensitivity collimator and a tomographic step-and-shoot continuous (SSC) mode acquisition. The purpose of this study is to determine whether SSC mode can be used in clinical practice with shorter examination times, while preserving image quality and ensuring accurate semi-quantification. Twenty bone scan and 10 lung scan studies were randomly selected over a period of 2 months. Three sets of image datasets were produced: step-and-shoot (SS) acquisition, simulated 25% count reduction using the Poisson resampling method (SimSS), and SimSS continuous acquisition (SimSSC), where SimSS was summed with counts acquired during detector head rotation. Visual assessment (5-point Likert scale, 2 readers) and semi-quantitative evaluation (50 focal uptake from 10 bone studies), assessed by SUVmean, coefficient of variation (COV), and contrast-to-noise ratio (CNR), were performed using t test and Bland-Altman analysis. RESULTS: Intra-reader agreement was substantial for reader 1 (k = 0.71) and for reader 2 (k = 0.61). Inter-reader agreement was substantial for SS set (k = 0.93) and moderate for SimSSC (k = 0.52). Bland-Altman analysis showed a good interchangeability of SS and SimSSC SUV values. The mean CNR between SS and SimSSC was not significantly different: 42.9 ± 43.7 [23.7-62.1] vs. 43.1 ± 46 [22.9-63.3] (p = 0.46), respectively. COV values, assessing noise level, did not deviate significantly between SS and SimSSC: 0.20 ± 0.08 [0.18-0.23] vs. 0.21 ± 0.08, [0.18-0.23] (p = 0.15), respectively, whereas a significant difference was demonstrated between SS and SimSS: 0.20 ± 0.08 [0.18-0.23] vs. 0.23 ± 0.09 [0.20-0.25] (p < 0.0001), respectively. CONCLUSIONS: SSC mode acquisition decreases examination time by approximately 25% in bone and lung SPECT/CT studies compared to SS mode (~ 2 min per single-bed SPECT), without compromising image quality and signal quantification. This SPECT sensitivity improvement also offers the prospect of more comfortable exams, with less motion artifacts, especially in painful or dyspneic patients.

Carfilzomib-induced endothelial dysfunction, recovery of proteasome activity, and prediction of cardiovascular complications: a prospective study.

Carfilzomib (CFZ) improves survival in relapsed/refractory multiple myeloma but is associated with cardiovascular adverse events (CVAEs). We prospectively investigated the effect of CFZ on endothelial function and associations with CVAEs. Forty-eight patients treated with Kd (CFZ 20/56 mg/m2 and dexamethasone) underwent serial endothelial function evaluation, using brachial artery flow-mediated dilatation (FMD) and 26S proteasome activity (PrA) measurement in PBMCs; patients were followed until disease progression or cycle 6 for a median of 10 months. FMD and PrA decreased acutely after the first dose (p < 0.01) and FMD decreased at cycles 3 and 6 compared to baseline (p ≤ 0.05). FMD changes were associated with CFZ-induced PrA changes (p < 0.05) and lower PrA recovery during first cycle was associated with more prominent FMD decrease (p = 0.034 for group interaction). During treatment, 25 patients developed Grade ≥3 CVAEs. Low baseline FMD (HR 2.57 lowest vs. higher tertiles, 95% CI 1.081-6.1) was an independent predictor of CVAEs. During treatment, an acute FMD decrease >40% at the end of first cycle was also independently associated with CVAEs (HR = 3.91, 95% CI 1.29-11.83). Kd treatment impairs endothelial function which is associated with PrA inhibition and recovery. Both pre- and posttreatment FMD predicted CFZ-related CVAEs supporting its role as a possible cardiovascular toxicity biomarker.

Microstructural Changes in the Left Mesocorticolimbic Pathway are Associated with the Comorbid Development of Fatigue and Depression in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Lower reward responsiveness has been associated with fatigue in multiple sclerosis (MS). However, association of MS-related fatigue with damage to the mesocorticolimbic reward pathway (superolateral medial forebrain bundle [slMFB]) has not been assessed. We investigated the association of fatigue and depression with slMFB damage in MS patients stratified based on longitudinal fatigue patterns. METHODS: Patient stratification: 1. Sustained Fatigue (SF): latest two Modified Fatigue Impact Scale (MFIS) ≥ 38 (n = 26); 2. Reversible Fatigue (RF): latest MFIS < 38, and at least one previous MFIS ≥ 38 (n = 25); 3. Never Fatigued (NF): ≥ 5 consecutive MFIS < 38 (n = 42); 4. Healthy Controls (n = 6). Diffusion MRI-derived measures of fractional anisotropy (FA), axial (AD), mean (MD), and radial diffusivity (RD) of the slMFB were compared between the groups. Depression was assessed using the Center for Epidemiologic Studies-Depression Scale (CES-D). RESULTS: Depressed (CES-D ≥ 16) SF patients showed significantly higher MD and RD than nondepressed SF and RF, and depressed RF patients, and significantly lower FA than nondepressed SF and depressed RF patients in their left slMFB. Depressed SF patients showed significantly higher left slMFB MD and AD than healthy controls. CONCLUSION: Microstructural changes to the left slMFB may play a role in the comorbid development of fatigue and depression in MS.

A non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs.

Stroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood-brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia (Macaca fascicularis) based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: "symptomatic salvaged tissue" (SST) and "asymptomatic infarcted tissue" (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia-reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization.

Microstructural alterations in medial forebrain bundle are associated with interindividual pain sensitivity.

The perception of pain to noxious stimuli, also known as pain sensitivity, varies among individuals. The comprised brain structures and their white matter pathways are complex and elusive. Here, we aimed to investigate whether variation of microstructure of the medial forebrain bundle (MFB), a tract connecting the basal forebrain with the brain stem, is associated with interindividual pain sensitivity. We assessed interindividual pain sensitivity as a rating of pain intensity to heat stimuli (45, 47, and 48.9°C) in 38 healthy men (age: 27.05 ± 5.7 years). We also reconstructed the MFB using multitensor tractography from diffusion magnetic resonance imaging (dMRI) and calculated free-water corrected dMRI measures of fractional anisotropy (FAt ), radial diffusivity (RDt ), and axial diffusivity (ADt ). Lower ratings of interindividual pain intensity correlated with higher FAt and lower RDt of the MFB. As changes in FAt and RDt may reflect abnormalities in myelination, the results might be interpreted as that a lower pain rating is associated with higher degree of myelination of the MFB and could represent an inhibitory pathway of pain. Our results suggest that alteration of microstructure in the MFB contributes to the interindividual variation of pain perception.

Detecting microstructural white matter abnormalities of frontal pathways in children with ADHD using advanced diffusion models.

Studies using diffusion tensor imaging (DTI) have documented alterations in the attention and executive system in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). While abnormalities in the frontal lobe have also been reported, the associated white matter fiber bundles have not been investigated comprehensively due to the complexity in tracing them through fiber crossings. Furthermore, most studies have used a non-specific DTI model to understand white matter abnormalities. We present results from a first study that uses a multi-shell diffusion MRI (dMRI) data set coupled with an advanced multi-fiber tractography algorithm to probe microstructural measures related to axonal/cellular density and volume of fronto-striato-thalamic pathways in children with ADHD (N = 30) and healthy controls (N = 28). Head motion was firstly examined as a priority in order to assure that no group difference existed. We investigated 45 different white matter fiber bundles in the brain. After correcting for multiple comparisons, we found lower axonal/cellular packing density and volume in ADHD children in 8 of the 45 fiber bundles, primarily in the right hemisphere as follows: 1) Superior longitudinal fasciculus-II (SLF-II) (right), 2) Thalamus to precentral gyrus (right), 3) Thalamus to superior-frontal gyrus (right), 4) Caudate to medial orbitofrontal gyrus (right), 5) Caudate to precentral gyrus (right), 6) Thalamus to paracentral gyrus (left), 7) Caudate to caudal middlefrontal gyrus (left), and 8) Cingulum (bilateral). Our results demonstrate reduced axonal/cellular density and volume in certain frontal lobe white matter fiber tracts, which sub-serve the attention function and executive control systems. Further, our work shows specific microstructural abnormalities in the striato-thalamo-cortical connections, which have not been previously reported in children with ADHD.

Compulsivity in Alcohol Use Disorder and Obsessive Compulsive Disorder: Implications for Neuromodulation.

Alcohol use Disorder (AUD) is one of the leading causes of morbidity and mortality worldwide. The progression of the disorder is associated with the development of compulsive alcohol use, which in turn contributes to the high relapse rate and poor longer term functioning reported in most patients, even with treatment. While the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines AUD by a cluster of symptoms, parsing its heterogeneous phenotype by domains of behavior such as compulsivity may be a critical step to improve outcomes of this condition. Still, neurobiological underpinnings of compulsivity need to be fully elucidated in AUD in order to better design targeted treatment strategies. In this manuscript, we review and discuss findings supporting common mechanisms between AUD and OCD, dissecting the construct of compulsivity and focusing specifically on characteristic disruptions in habit learning and cognitive control in the two disorders. Finally, neuromodulatory interventions are proposed as a probe to test compulsivity as key pathophysiologic feature of AUD, and as a potential therapy for the subgroup of individuals with compulsive alcohol use, i.e., the more resistant stage of the disorder. This transdiagnostic approach may help to destigmatize the disorder, and suggest potential treatment targets across different conditions.

MRI Assessment of Oxygen Metabolism and Hemodynamic Status in Symptomatic Intracranial Atherosclerotic Stenosis: A Pilot Study.

BACKGROUND AND PURPOSE: Hemodynamic and metabolic impairment in intracranial atherosclerotic stenosis (ICAS) may promote stroke vulnerability particularly in borderzone areas. Perfusion and oxygen mapping magnetic resonance imaging (MRI) may provide useful information in this setting. METHODS: In this pilot study, patients with symptomatic atherosclerotic anterior circulation stenosis ≥60%, without other sources of ischemic stroke, were included. High-resolution vessel wall MRI quantified the stenosis degree, and hemodynamic and metabolic impairment was assessed at baseline using dynamic susceptibility contrast perfusion and multiparametric quantitative blood-oxygen-level-dependent (mqBOLD) oxygenation MRI. All parameters were assessed within both hemispheres and in borderzone areas. RESULTS: Forty-three subjects with intracranial artery narrowing were screened from November 2014 to January 2016. Eleven patients met the study criteria (mean ± standard deviation age = 64.4 ± 10.6 years, the mean degree of stenosis was 76.9 ± 23.4%). No interhemispheric differences were observed across oxygen (cerebral metabolic rate of oxygen and tissular saturation of oxygen) or perfusion (mean transit time, time to maximum, Tmax , normalized cerebral blood volume [nCBV], and normalized cerebral blood flow) parameters. A positive correlation was observed between the stenosis degree and ipsilateral nCBV (R = .77, P = .008). In addition, a significant increase in CBV was observed in anterior cortical borderzones ipsilateral to stenosis (nCBV = 7.20 ± 1.81 vs. 5.45 ± 1.40 mL/100 g, P = .02). CONCLUSION: Symptomatic ICAS had no global impact on perfusion and oxygen mapping MRI at resting state. A significant increase in nCBV was found within anterior borderzone areas.