Autism is a neurodevelopmental disorder that has been associated with atypical brain functioning. Functional connectivity MRI (fcMRI) studies examining neural networks in autism have seen an exponential rise over the last decade. Such investigations have led to characterization of autism as a distributed neural systems disorder. Studies have found widespread cortical underconnectivity, local overconnectivity, and mixed results suggesting disrupted brain connectivity as a potential neural signature of autism. In this review, we summarize the findings of previous fcMRI studies in autism with a detailed examination of their methodology, in order to better understand its potential and to delineate the pitfalls. We also address how a multimodal neuroimaging approach (incorporating different measures of brain connectivity) may help characterize the complex neurobiology of autism at a global level. Finally, we also address the potential of neuroimaging-based markers in assisting neuropsychological assessment of autism. The quest for a biomarker for autism is still ongoing, yet new findings suggest that aberrant brain connectivity may be a promising candidate.

Previous studies have observed impairments in both brain function and neurometabolite levels in schizophrenia. In this study, we investigated the relationship between brain activity and neurochemistry in off-medication patients with schizophrenia and if this relationship is altered following antipsychotic medication by combining proton magnetic resonance spectroscopy (1H-MRS) with functional magnetic resonance imaging (fMRI). We used single voxel MRS acquired in the bilateral dorsal anterior cingulate cortex (ACC) and fMRI during performance of a Stroop color-naming task in 22 patients with schizophrenia (SZ), initially off-medication and after a 6-week course of risperidone, and 20 matched healthy controls (HC) twice, 6 weeks apart. We observed a significant decrease in ACC glutamate + glutamine (Glx)/Creatine (Cr) levels in medicated SZ patients compared to HC but not compared to their off-medication baseline. In off-medication SZ, the relationship between ACC Glx/Cr levels and the blood oxygen level-dependent (BOLD) response in regions of the salience network (SN) and posterior default mode network (DMN) was opposite than of HC. After 6 weeks, the relationship between Glx and the BOLD response was still opposite between the groups; however for both groups the direction of the relationship changed from baseline to week 6. These results suggest a mechanism whereby alterations in the relationship between cortical glutamate and BOLD response is disrupting the modulation of major neural networks subserving cognitive processes, potentially affecting cognition. While these relationships appear to normalize with treatment in patients, the interpretations of the results are confounded by significant group differences in Glx levels, as well as the variability of the relationship between Glx and BOLD response in HC over time, which may be driven by factors including habituation to task or scanner environment.

To better understand cognitive control impairment in schizophrenia, it is vital to determine the extent of dysfunctional connectivity in the associated fronto-striatal brain network, with a focus on the connections with the anterior cingulate cortex (ACC), prior to the potential confounding effect of medication. It is also essential to determine the effects following antipsychotic medication and the relationship of those effects on psychosis improvement. Twenty-two patients with schizophrenia, initially unmedicated and after a 6-week course of risperidone, and 20 matched healthy controls (HC) performed a fMRI task twice, six weeks apart. We investigated group and longitudinal differences in ACC-related functional connectivity during performance of a Stroop color task as well as connectivity patterns associated with improvement in psychosis symptoms. Unmedicated patients with schizophrenia showed greater functional connectivity between ACC and bilateral caudate and midbrain and lower connectivity with left putamen compared to healthy controls. At baseline, greater functional connectivity between ACC and bilateral putamen predicted subsequent better treatment response. Change in functional connectivity between ACC and left putamen positively correlated with better treatment response. These results suggest that patterns of functional connectivity in fronto-striatal networks can be utilized to predict potential response to antipsychotic medication. Prior to treatment, brain function may be structured with a predisposition that favors or not treatment response.

To understand the mechanism of cognitive control dysfunction in schizophrenia, it is critical to characterize brain function without the confounding effect of medication. It is also important to establish the extent to which antipsychotic medication restores brain function and whether those changes are related to psychosis improvement. Twenty-two patients with schizophrenia, initially unmedicated and after a 6-week course of risperidone, and 20 healthy controls (HC) studied twice, 6 weeks apart, performed an fMRI task. We examined group and longitudinal differences in anterior cingulate cortex (ACC), striatum, and midbrain functional activity during performance of a Stroop color task as well as activity patterns associated with improvement in psychosis symptoms. Unmedicated patients showed reduced functional activity in the ACC, striatum, and midbrain compared to HC. Post hoc contrasts from significant group-by-time interactions indicated that, in patients, drug administration was associated with both activity increases and decreases. In unmedicated patients, greater baseline functional activity in the striatum and midbrain predicted subsequent better treatment response. Greater changes in functional activity in ACC and ventral putamen over the course of 6 weeks positively correlated with better treatment response. Unmedicated patients show reduced activity in brain networks pivotal for cognitive control and medication is associated with functional changes in these regions. These results suggest a mechanism by which antipsychotic medication has a beneficial effect on cognition. Our results also support the notion that treatment response is determined by a combination of the baseline pattern of brain function and by the pharmacological modulation of these regions.

(HCs; 5 males and 5 females) were included in the current study. All participants had a study visit that included a blood draw for serum KYNA and kynurenine levels, physiological measurements, demographic data, assessments of current anxiety and perceived stress measured by the State Trait Anxiety Inventory/Visual Analog Scale (STAI_VAS) and the Perceived Stress Scale (PSS), childhood trauma history measured by the Childhood Trauma Questionnaire (CTQ), and medication use. Results: In this pilot study, differences in KYNA and kynurenine between SCZ and HCs were not statistically significant (P > .05). Within SCZ, kynurenine levels were correlated with the total CTQ score (r = .63, P = .049) as well as the physical abuse domain (r = .74, P = .016). KYNA also tended to correlate with the total CTQ (r = .60, P = .069), emotional abuse (r = .42, P = .045), and physical abuse domains (r = .62, P = .058. There were not significant correlations noted between KYNA or kynurenine and CTQ scores in the HC groups. Kynurenine levels were positively correlated with the STAI tense domain also in SCZ subjects (r = .81, P = .004). With regard to differences in medication use, serum KYNA and kynurenine levels were significantly lower in people with schizophrenia taking medications for constipation (P < .05) and anticholinergic medications compared to patients not taking these medications. Conclusion: In this small sample, greater childhood trauma and/or perceived stress symptoms were found to be related to higher levels of serum KYNA and kynurenine in patients with schizophrenia. Further research is needed in a larger sample to assess whether childhood trauma and subsequent stress and/or anxiety symptoms relate to KYNA and kynurenine levels in patients with schizophrenia. Our data suggest that future investigations should also examine the effect of concomitant medications (particularly those with anticholinergic activity) on KYNA and kynurenine levels in schizophrenia. This information will help future investigations identifying psychopathological pathways, leading to studying specific schizophrenia phenotypes and deconstructing the illness. SA64. HALLUCINATION SEVERITY Background:Previous functional imaging studies of auditory hallucinations in psychosis patients have demonstrated abnormal activation patterns in the primary auditory cortex; in order to investigate the mechanisms that predispose hallucinations, we examine if alterations in resting connectivity to auditory cortex predict hallucination severity in a large sample of psychosis patients. Methods: Whole brain resting state connectivity to primary and secondary auditory cortex defined as Brodmann Areas 22, 41, and 42 were evaluated for 392 psychosis subjects and 219 healthy controls. Subjects were recruited as part of the multisite Bipolar & Schizophrenia Network on Intermediate Phenotypes (BSNIP1) study. Univariate multiple regression analysis evaluated where brain resting state connectivity to the auditory cortex was a significant predictor of hallucination severity a...