Structural and functional dysconnectivity of the fronto-thalamic system in schizophrenia: a DCM-DTI study.

Evidence suggests that cognitive deficits are a core feature of schizophrenia. The concept of "cognitive dysmetria" has been introduced to characterize disintegration of fronto-thalamic-cerebellar circuitry which constitutes a key network for a variety of neuropsychological symptoms in schizophrenia. The present multimodal study aimed at investigating effective and structural connectivity of the fronto-thalamic circuitry in schizophrenia. fMRI effective connectivity analysis using dynamic causal modeling (DCM) and diffusion tensor imaging (DTI) were combined to examine cognitive control processes in 38 patients with schizophrenia and 40 matched healthy controls. Significantly lower fractional anisotropy (FA) was detected in patients in the right anterior limb of the internal capsule (ALIC), the right thalamus and the right corpus callosum. During Stroop task performance patients demonstrated significantly lower activation relative to healthy controls in a predominantly right lateralized fronto-thalamo-cerebellar network. An abnormal effective connectivity was observed in the right connections between thalamus, anterior cingulate and dorsolateral prefrontal cortex. FA in the ALIC was significantly correlated with the thalamic BOLD signal, cognitive performance and fronto-thalamic effective connectivity in patients. Present data provide evidence for the notion of a structural and functional defect in the fronto-thalamo-cerebellar circuitry, which may be the basis of specific cognitive impairments in schizophrenia.

Neonatal physiological correlates of near-term brain development on MRI and DTI in very-low-birth-weight preterm infants.

Structural brain abnormalities identified at near-term age have been recognized as potential predictors of neurodevelopment in children born preterm. The aim of this study was to examine the relationship between neonatal physiological risk factors and early brain structure in very-low-birth-weight (VLBW) preterm infants using structural MRI and diffusion tensor imaging (DTI) at near-term age. Structural brain MRI, diffusion-weighted scans, and neonatal physiological risk factors were analyzed in a cross-sectional sample of 102 VLBW preterm infants (BW ≤ 1500 g, gestational age (GA) ≤ 32 weeks), who were admitted to the Lucile Packard Children's Hospital, Stanford NICU and recruited to participate prior to routine near-term brain MRI conducted at 36.6 ± 1.8 weeks postmenstrual age (PMA) from 2010 to 2011; 66/102 also underwent a diffusion-weighted scan. Brain abnormalities were assessed qualitatively on structural MRI, and white matter (WM) microstructure was analyzed quantitatively on DTI in six subcortical regions defined by DiffeoMap neonatal brain atlas. Specific regions of interest included the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, the thalamus, and the globus pallidus. Regional fractional anisotropy (FA) and mean diffusivity (MD) were calculated using DTI data and examined in relation to neonatal physiological risk factors including gestational age (GA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis, as well as serum levels of C-reactive protein (CRP), glucose, albumin, and total bilirubin. Brain abnormalities were observed on structural MRI in 38/102 infants including 35% of females and 40% of males. Infants with brain abnormalities observed on MRI had higher incidence of BPD (42% vs. 25%) and sepsis (21% vs. 6%) and higher mean and peak serum CRP levels, respectively, (0.64 vs. 0.34 mg/dL, p = .008; 1.57 vs. 0.67 mg/dL, p= .006) compared to those without. The number of signal abnormalities observed on structural MRI correlated to mean and peak CRP (rho = .316, p = .002; rho = .318, p= .002). The number of signal abnormalities observed on MRI correlated with thalamus MD (left: r= .382, p= .002; right: r= .400, p= .001), controlling for PMA-at-scan. Thalamus WM microstructure demonstrated the strongest associations with neonatal risk factors. Higher thalamus MD on the left and right, respectively, was associated with lower GA (r = -.322, p = .009; r= -.381, p= .002), lower mean albumin (r = -.276, p= .029; r= -.385, p= .002), and lower mean bilirubin (r = -.293, p= .020; r= -.337 p= .007). Results suggest that at near-term age, thalamus WM microstructure may be particularly vulnerable to certain neonatal risk factors. Interactions between albumin, bilirubin, phototherapy, and brain development warrant further investigation. Identification of physiological risk factors associated with selective vulnerability of certain brain regions at near-term age may clarify the etiology of neurodevelopmental impairment and inform neuroprotective treatment for VLBW preterm infants.

Surgery for psychiatric disorders.

Surgery in psychiatric disorders has a long history and has regained momentum in the past few decades with deep brain stimulation (DBS). DBS is an adjustable and reversible neurosurgical intervention using implanted electrodes to deliver controlled electrical pulses to targeted areas of the brain. It holds great promise for therapy-refractory obsessive-compulsive disorder. Several double-blind controlled and open trials have been conducted and the response rate is estimated around 54%. Open trials have shown encouraging results with DBS for therapy-refractory depression and case reports have shown potential effects of DBS on addiction. Another promising indication is Tourette syndrome, where potential efficacy of DBS is shown by several case series and a few controlled trials. Further research should focus on optimizing DBS with respect to target location and increasing the number of controlled double-blinded trials. In addition, new indications for DBS and new target options should be explored in preclinical research.