Diffusion tensor imaging tractography of the fornix and belief confidence in first-episode psychosis.

Previous studies have demonstrated that patients with psychosis are more confident in beliefs and judgments compared to healthy participants and psychiatric controls with major depression. A recent study conducted by our research group has provided evidence for hippocampal pathology in association with overconfidence in a first-episode psychosis sample. The fornix is the primary efferent neural pathway of the hippocampus and may also play a role in self-certainty pathophysiology. The current investigation applied diffusion tensor imaging tractography to a first-episode psychosis sample to explore whether integrity of the fornix is associated with self-certainty. High resolution structural magnetic resonance and diffusion tensor images were obtained in 44 people with a first-episode psychosis. Diffusion tensor imaging tractography was used to estimate fractional anisotrophy (FA), a measure of white matter integrity, in the fornix. Confidence in beliefs and judgments was measured with the self-certainty subscale of the Beck Cognitive Insight Scale (BCIS). The analysis showed that self-certainty significantly correlated to FA values in the right fornix but was nonsignificant for the left fornix. The findings indicate anatomical dysconnectivity of the right fornix in correlation with BCIS-rated self-certainty in our first-episode psychosis sample. When considered with our previously published self-certainty-hippocampus result in a first-episode psychosis sample, overlapping with that of this study, the results indicate a concurrence of volumetric reductions in hippocampus and fornix pathology in correlation with self-certainty.

Fronto-temporal disconnectivity and clinical short-term outcome in first episode psychosis: a DTI-tractography study.

Determining reliable markers of clinical outcome for psychosis is essential to adjust intervention efforts. White matter alterations exist prior to psychosis onset but its association with clinical outcome in the very early phase of psychosis is currently unknown. In the present study, white matter was assessed by diffusion tensor imaging (DTI) in patients with first episode psychosis (FEP) and healthy controls. Forty-four FEP patients and 30 matched healthy controls completed a DTI scan. The patient group was split in poor (n = 24) and good (n = 20) outcome subgroups based on 6-month clinical data. DTI tractography was used to estimate fractional anisotropy (FA) in the three main tracts connecting frontal and temporal regions (i.e. the cingulum, the superior longitudinal fasciculus and the uncinate fasciculus). The analyses showed selective FA reductions in both the uncinate and the superior longitudinal fasciculi, but not in the cingulum, when comparing FEP patients to healthy controls. FEP subgroup analyses revealed greater white matter changes in these tracts in patients with poor outcome as compared to patients with good outcome. These findings confirm that abnormal fronto-temporal connectivity contributes to the physiopathology of FEP and constitutes an early marker of clinical short-term outcome.

Neural markers of remission in first-episode schizophrenia: a volumetric neuroimaging study of the hippocampus and amygdala.

OBJECTIVE: The temporolimbic region has been implicated in the pathophysiology in schizophrenia. More specifically, significantly smaller hippocampal volumes but not amygdala volumes have been identified at onset in first-episode schizophrenia (FES) patients. However, volumetric differences (namely, in the hippocampus) exhibit an ambiguous relationship with long-term outcome. So, we examined the relationship between hippocampus and amygdala volumes and early remission status. METHODS: We compared hippocampus and amygdala volumes between 40 non-remitted and 17 remitted FES patients and 57 healthy controls. Amygdala and hippocampus were manually traced with the hippocampus additionally segmented into three parts: body, head, and tail. Remission was defined as mild or less on both positive and negative symptoms over a period of 6 consecutive months as per the 2005 Remission in Schizophrenia Working Group criteria. RESULTS: A significant [group x structure x side] interaction revealed outcome groups differed in hippocampus tail volumes; significantly on the left (non-remitted=694+/-175 mm(3); remitted=855+/-133 mm(3); p=0.001) with a trend difference on the right (non-remitted=723+/-162 mm(3); remitted=833+/-126 mm(3); p=0.023). Groups did not differ in body, head, or amygdala volumes bi-laterally. CONCLUSIONS: A smaller hippocampal tail volume may represent a neural marker in FES patients who do not achieve early remission after the first 6 months of treatment. The early identification of patients with poor outcome with respect to the hippocampus tail may encourage the search for new, more target-specific, medications in hope of improving outcome and moving us towards a better understanding of the pathophysiology of schizophrenia.

Can voxel based morphometry, manual segmentation and automated segmentation equally detect hippocampal volume differences in acute depression?

CONTEXT: According to meta-analyses, depression is associated with a smaller hippocampus. Most magnetic resonance imaging (MRI) studies among middle aged acute depressed patients are based on manual segmentation of the hippocampus. Few studies used automated methods such as voxel-based morphometry (VBM) or automated segmentation that can overcome certain drawbacks of manual segmentation (essentially intra- and inter-rater variability and operator time consumption). OBJECTIVE: The aim of our study was to compare the sensitivity of manual segmentation, automated segmentation and VBM to detect hippocampal structural changes in middle aged acute depressed population. METHOD: Twenty-one middle aged depressed inpatients and 21 matched controls were compared regarding their hippocampal structure using VBM with SPM5, manual segmentation and an automated segmentation algorithm. The VBM-ROI analysis was performed using two different normalization methods: the standard approach implemented in SPM5 and the most recent DARTEL algorithm. RESULTS: Using VBM-DARTEL, when corrected for multiple comparisons, significant volume differences were detected between groups in different regions and more specifically in hippocampus with ROI analyses. Whereas using standard VBM (without DARTEL), ROI analyses did not show bilateral volume between group differences. Significant hippocampal volume reductions between patients and controls were also detected using manual segmentation (-11.6% volume reduction, p<0.05) and automated segmentation (-9.7% volume reduction, p<0.05). VBM-DARTEL and automated segmentation show equal sensitivity in detecting hippocampal differences in depressed patients, while standard VBM was unable to detect hippocampal changes. Both VBM-DARTEL and automated segmentation could be used to perform large scale volumetric studies in humans. The new automated segmentation technique could further explore and detect hippocampal subpart differences that could be very useful for clarifying physiopathology of psychiatric disorders.

Selective abnormal modulation of hippocampal activity during memory formation in first-episode psychosis.

CONTEXT: Memory is one of the cognitive functions most affected in schizophrenia, with deficits observed from the first episode of psychosis (FEP). Previous studies have indicated that some memory processes may be more affected than others. OBJECTIVE: To examine the neural correlates of 3 specific memory processes in FEP by means of functional magnetic resonance imaging (fMRI). DESIGN: Case-control study. SETTING: Prevention and Early Intervention Program for Psychoses of the Douglas Hospital and Montreal Neurological Institute, McGill University. Subjects Twenty-six patients with FEP and 20 healthy controls. MAIN OUTCOME MEASURES: Behavioral performance and regional brain activity measured during memory encoding by fMRI. Our fMRI design included 3 within-subject contrasts (associative vs item-oriented encoding, encoding of arbitrary vs semantically related image pairs, and successful vs unsuccessful memory encoding) that were then used for group conjunctions and between-group analyses. RESULTS: Patients with FEP showed normal activation of several brain regions, including the prefrontal cortex, hippocampus, and parahippocampal cortex, during successful memory encoding and associative encoding. In contrast, the hippocampus and surrounding medial temporal areas showed reduced activity during the encoding of arbitrary pairs. This selective dysfunction reflected by abnormal brain activation during encoding was accompanied by a greater deficit for subsequent recognition of arbitrary pairs relative to the semantically related pairs. CONCLUSIONS: This study demonstrated that, in the same group of patients with FEP, the hippocampus could show either normal or abnormal modulation of activation depending on the specific cognitive process that was examined. The normal modulation of hippocampal activation observed during successful memory encoding in FEP argues against a general inability to recruit this region. Instead, the dysfunction was specifically linked to semantic relatedness. This selective deficit seems to affect memory performance in FEP and denotes an important representational problem that may confer greater vulnerability to psychotic disorders and would thus be interesting to examine in high-risk populations.