The role of head circumference and cerebral volumes to phenotype male adults with autism spectrum disorder

Background: Autism spectrum disorder (ASD) has been repeatedly associated with enlargements of head circumference in children with ASD. However, it is unclear if these enlargements persist into adulthood. This is the first study to investigate head circumference in a large sample of adults with ASD. Methods: We apply a fully automated magnetic resonance imaging (MRI) based measurement approach to compute head circumference by combining 3D and 2D image processing. Head circumference was compared between male adults with ASD (n = 120) and healthy male controls (n = 136), from the Autism Brain Imaging Data Exchange (ABIDE) database. To explain which brain alterations drive our results, secondary analyses were performed for 10 additional morphological brain metrics. Results: ASD subjects showed an increase in head circumference (p = .0018). In addition, ASD patients had increased ventricular surface area (SA) (p = .0013). Intracranial volume, subarachnoidal cerebrospinal fluid (CSF) volume, and gray matter volume explained 50% of head circumference variance. Using a linear support vector machine, we gained an ASD classification accuracy of 73% (sensitivity 92%, specificity 68%) using head circumference and brain-morphological metrics as input features. Head circumference, ventricular SA, ventricular CSF volume, and ventricular asymmetry index contributed to 85% of feature weighting relevant for classification. Conclusion: Our results suggest that head circumference increases in males with ASD persist into adulthood. Results may be driven by morphological alterations of ventricular CSF. The presented approach for an automated head circumference measurement allows for the retrospective investigation of large MRI datasets in neuropsychiatric disorders

Associations of thalamocortical networks with reduced mindfulness in alcohol use disorder.

BACKGROUND Increased mindfulness is associated with reduced alcohol consumption in patients with alcohol use disorder (AUD) after residential treatment. However, the underlying neurobiological mechanism of mindfulness in AUD is unclear. Therefore, we investigate the structural and functional alterations of the thalamocortical system with a focus on the mediodorsal thalamic nucleus (MD-TN), the default mode and the salience network (DMN/SN) which has previously been associated with mindfulness in healthy subjects. We hypothesized lower mindfulness and reduced structural and functional connectivity (FC) of the thalamocortical system, particularly in the DMN/SN in AUD. We assumed that identified neurobiological alterations in AUD are associated with impairments of mindfulness. METHODS Forty-five abstinent patients with AUD during residential treatment and 20 healthy controls (HC) were recruited. Structural and resting-state functional MRI-scans were acquired. We analysed levels of mindfulness, thalamic volumes and network centrality degree of the MD-TN using multivariate statistics. Using seed-based whole brain analyses we investigated functional connectivity (FC) of the MD-TN. We performed exploratory correlational analyses of structural and functional DMN/SN measurements with levels of mindfulness. RESULTS In AUD we found significantly lower levels of mindfulness, lower bilateral thalamic and left MD-TN volumes, reduced FC between MD-TN and anterior cingulum/insula and lower network centrality degree of the left MD-TN as compared to HC. In AUD, lower mindfulness was associated with various reductions of structural and functional aspects of the MD-TN. CONCLUSION Our results suggest that structural and functional alterations of a network including the MD-TN and the DMN/SN underlies disturbed mindfulness in AUD

Hippocampal volume and parahippocampal cingulum alterations are associated with avoidant attachment in patients with depression

Background: Insecure attachment style (anxious and avoidant) predisposes to the development of depression and has been linked to hippocampal alterations in healthy individuals. However, it is unclear if there are alterations of the hippocampus and the parahippocampal cingulum (PHC) in patients with depression. Methods: Forty-eight patients with major depressive disorder and 18 healthy controls underwent MP2RAGE and diffusion-weighted magnetic resonance imaging. Attachment characteristics were assessed with the revised adult attachment scale. Patients were classified into subgroups with low (anxious: n = 27; avoidant: n = 21) and high (anxious: n = 20; avoidant: n = 28) attachment characteristics. Bilateral PHC were reconstructed using manual tractography. Hippocampal volumes, mean fractional anisotropy and mean diffusivity (MD) in bilateral PHC were compared between attachment subgroups and healthy controls. Results: Patients had higher scores of anxious and avoidant attachment, which were associated with depression severity. Patients with high avoidance had decreases in hippocampal volumes in comparison to patients with low avoidance. Furthermore, patients with high avoidance had increased MD in bilateral PHC in comparison to patients with low avoidance and in comparison to healthy controls. Limitations: Assessment of attachment characteristics may be influenced by cognitive biases due to depressive symptoms Conclusions: High attachment avoidance in patients with depression is associated with volume reductions in the hippocampus and impaired PHC-microstructure

Reduced structural connectivity of the amygdala is associated with childhood trauma in adult patients with alcohol use disorder.

Childhood trauma (CT) is frequent in patients with alcohol use disorder (AUD) and may impact on adult drinking behaviour and treatment outcome. This study aimed to investigate the structural correlates of CT in AUD, focusing on the amygdala, which plays a crucial role in the neurobiology of trauma. We hypothesized reduced amygdala volume and reduced structural connectivity as quantified by fractional anisotropy (FA) and by number of streamlines in those AUD patients with a history of moderate to severe CT (AUD-CT). T1-weighted MP2RAGE and diffusion-weighted imaging (DWI) 3-Tesla MRI-scans were acquired in 41 recently abstinent patients with AUD. We compared bilateral amygdala volume and structural connectivity (FA and number of streamlines) of pathways emanating from the amygdala between AUD-CT (n = 20) and AUD without CT (AUD-NT, n = 21) using a mixed model multivariate analysis of variance (MANCOVA) controlling for age and gender. AUD-CT displayed reduced FA and reduced number of streamlines of amygdalar tracts. There were no differences regarding amygdala volume. The severity of physical abuse, a subscale of the childhood trauma questionnaire, was negatively correlated with FA and with number of streamlines. AUD-CT and AUD-NT differ regarding structural connectivity of pathways projecting to and from the amygdala, but not regarding amygdala volume. Those alterations of structural connectivity in AUD-CT may represent a distinguishable neurobiological subtype of AUD, which might be associated with the complex clinical picture and poorer outcome that patients with CT and AUD often present

Reduction in Cerebral Perfusion after Heroin Administration: A Resting State Arterial Spin Labeling Study

Heroin dependence is a chronic relapsing brain disorder, characterized by the compulsion to seek and use heroin. Heroin itself has a strong potential to produce subjective experiences characterized by intense euphoria, relaxation and release from craving. The neurofunctional foundations of these perceived effects are not well known. In this study, we have used pharmacological magnetic resonance imaging (phMRI) in 15 heroin-dependent patients from a stable heroin-assisted treatment program to observe the steady state effects of heroin (60 min after administration). Patients were scanned in a cross-over and placebo controlled design. They received an injection of their regular dose of heroin or saline (placebo) before or after the scan. As phMRI method, we used a pulsed arterial spin labeling (ASL) sequence based on a flow-sensitive alternating inversion recovery (FAIR) spin labeling scheme combined with a single-shot 3D GRASE (gradient-spin echo) readout on a 3 Tesla scanner. Analysis was performed with Statistical Parametric Mapping (SPM 8), using a general linear model for whole brain comparison between the heroin and placebo conditions. We found that compared to placebo, heroin was associated with reduced perfusion in the left anterior cingulate cortex (ACC), the left medial prefrontal cortex (mPFC) and in the insula (both hemispheres). Analysis of extracted perfusion values indicate strong effect sizes and no gender related differences. Reduced perfusion in these brain areas may indicate self- and emotional regulation effects of heroin in maintenance treatment

Abnormal Functional Integration of Thalamic Low Frequency Oscillation in the BOLD Signal After Acute Heroin Treatment

Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross-over, double-blind, vehicle-controlled study, 29 heroin-maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting-state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed-based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin-associated increase in fALFF was mainly dominated by slow-4 (0.027-0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction

Reduced tract length of the medial forebrain bundle and the anterior thalamic radiation in bipolar disorder with melancholic depression.

BACKGROUND The supero-lateral medial forebrain bundle (slMFB) and the anterior thalamic radiation (ATR) play a core role in reward anticipation and motivational processes. In this study, the slMFB and the ATR were investigated in a group of depressed bipolar disorder (BD) and in healthy controls (HC) using tract length as a measure of fibre geometry and fractional anisotropy (FA) as a measure of white matter microstructure. We hypothesized reduced tract length and FA of the slMFB and the ATR in BD. We expect alterations to be driven by the melancholic subtype. METHODS Nineteen depressed patients with BD and 19 HC matched for age and gender underwent diffusion-weighted magnetic resonance imaging (MRI) scans. Diffusion tensor imaging (DTI) based tractography was used to reconstruct bilateral slMFB and ATR. Mean tract length and FA were computed for the slMFB and the ATR. Mixed-model ANCOVAs and post-hoc ANCOVAs, controlling for age and intracranial volume, were used to compare tract length and FA of bilateral slMFB and ATR between HC and BD and between HC and subgroups with melancholic and non-melancholic symptoms. RESULTS In BD we found a significantly shortened tract length of the right slMFB and ATR in BD compared to HC. Subgroup analyses showed that these findings were driven by the melancholic subgroup. Mean-FA did not differ between HC and BD. LIMITATIONS Sample size CONCLUSIONS: Tract length of the right slMFB and the right ATR is reduced in BD. Those changes of fibre geometry are driven by the melancholic subtype

The role of the orbitofrontal cortex and the nucleus accumbens for craving in alcohol use disorder.

This study aimed to investigate structural and functional alterations of the reward system and the neurobiology of craving in alcohol use disorder (AUD). We hypothesized reduced volume of the nucleus accumbens (NAcc), reduced structural connectivity of the segment of the supero-lateral medial forebrain bundle connecting the orbitofrontal cortex (OFC) with the NAcc (OFC-NAcc), and reduced resting-state OFC-NAcc functional connectivity (FC). Furthermore, we hypothesized that craving is related to an increase of OFC-NAcc FC. Thirty-nine recently abstinent patients with AUD and 18 healthy controls (HC) underwent structural (T1w-MP2RAGE, diffusion-weighted imaging (DWI)) and functional (resting-state fMRI) MRI-scans. Gray matter volume of the NAcc, white matter microstructure (fractional anisotropy (FA)) and macrostructure (tract length) of the OFC-NAcc connection and OFC-NAcc FC were compared between AUD and HC using a mixed model MANCOVA controlling for age and gender. Craving was assessed using the thoughts subscale of the obsessive-compulsive drinking scale (OCDS) scale and was correlated with OFC-NAcc FC. There was a significant main effect of group. Results were driven by a volume reduction of bilateral NAcc, reduced FA in the left hemisphere, and reduced tract length of bilateral OFC-NAcc connections in AUD patients. OFC-NAcc FC did not differ between groups. Craving was associated with increased bilateral OFC-NAcc FC. In conclusion, reduced volume of the NAcc and reduced FA and tract length of the OFC-NAcc network suggest structural alterations of the reward network in AUD. Increased OFC-NAcc FC is associated with craving in AUD, and may contribute to situational alcohol-seeking behavior in AUD

Link between structural connectivity of the medial forebrain bundle, functional connectivity of the ventral tegmental area, and anhedonia in unipolar depression.

The ventral tegmental area (VTA), nucleus accumbens (NAcc), and prefrontal cortex (PFC) are essential for experiencing pleasure and initiating motivated behaviour. The VTA, NAcc, and PFC are connected through the medial forebrain bundle (MFB). In humans, two branches have been described: an infero-medial branch (imMFB) and a supero-lateral branch (slMFB). This study aimed to explore the associations between structural connectivity of the MFB, functional connectivity (FC) of the VTA, anhedonia, and depression severity in patients with depression. Fifty-six patients with unipolar depression and 22 healthy controls matched for age, sex, and handedness were recruited at the University Hospital of Psychiatry and Psychotherapy in Bern, Switzerland. Diffusion-weighted imaging and resting-state functional magnetic resonance imaging scans were acquired. Using manual tractography, the imMFB and slMFB were reconstructed bilaterally for each participant. Seed-based resting-state FC was computed from the VTA to the PFC. Hedonic tone was assessed using the Fawcett-Clark Pleasure Scale. We identified reduced tract volume and reduced number of tracts in the left slMFB. There was an increase in FC between the VTA and right medial PFC in patients with depression. Depression severity was associated with reduced tract volume and fewer tracts in the left slMFB. Reduced hedonic tone was associated with reduced tract volume. Conversely, reduced hedonic tone was associated with increased FC between the VTA and the PFC. In conclusion, our results suggest reduced structural connectivity of the slMFB in patients with depression. Increases in FC between the VTA and PFC may be associated with anhedonia or compensatory hyperactivity

Quantification of cerebral veins in patients with acute migraine with aura: A fully automated quantification algorithm using susceptibility-weighted imaging.

INTRODUCTION Susceptibility weighted imaging (SWI) is a very sensitive technique that often depicts prominent focal veins (PFV) in patients with acute migraine with aura (MwA). Interpretation of visual venous asymmetry (VVA) between brain hemispheres on SWI may help support the clinical diagnosis of MwA. Our goal was to develop an automated algorithm for segmentation and quantification of cerebral veins using SWI. MATERIALS AND METHODS Expert readers visually evaluated SWI of patients with acute MwA for VVA. Subsequently a fully automated algorithm based on 3D normalization and 2D imaging processing using SPM and MATLAB image processing software including top-hat transform was used to quantify cerebral veins and to calculate volumetric differences between hemispheres. RESULTS Fifty patients with MwA were examined with SWI. VVA was present in 20 of 50 patients (40%). In 95% of patients with VVA, the fully automated calculation agreed with the side that visually harboured more PFV. Our algorithm showed a sensitivity of 95%, specificity of 90% and accuracy of 92% for detecting VVA. Patients with VVA had significantly larger vein volume on the hemisphere with more PFV compared to patients without (15.90 ± 5.38 ml vs 11.93 ± 5.31 ml; p = 0.013). The mean difference in venous volume between hemispheres in patients with VVA was larger compared to patients without VVA (16.34 ± 7.76% vs 4.31 ± 3.26% p < 1E-10). The average time between aura onset and SWI correlated negatively with venous volume of the dominant brain hemisphere (r = -0.348; p = 0.038). CONCLUSION A fully automated algorithm can accurately identify and quantify cerebral venous distribution on SWI. Absolute quantification may be useful for the future assessment of patients with suspected diseases, which may be associated with a unilateral abnormal degree of venous oxygenation