Computational protocol: Altered activation and connectivity in a hippocampal–basal ganglia–midbrain circuit during salience processing in subjects at ultra high risk for psychosis

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Protocol publication

[…] Detailed descriptions of the fMRI data acquisition and pre-processing are provided in the . For between-group comparisons, a two-sample t-test was performed at the second (group) level for each of the main effects of interest, reward, aversion and novelty, while covarying for age. As education may be expected to differ between groups, this was not included as a covariate in the main analysis. We performed whole-brain analyses at an uncorrected threshold of P<0.005 and applied small volume correction at a threshold of family-wise error (FWE) <0.05 within three pre-specified bilateral regions of interest: the midbrain, hippocampus/parahippocampal gyrus and ventral striatum/pallidum. Bonferroni correction was then applied for these three regions of interest (ROIs). For the hippocampus/parahippocampal regions of interest, we used anatomical masks from the automated anatomical labelling toolbox implemented in SPM 8[ref. ] (). For the midbrain ROI, we visualized the substantia nigra/ventral tegmental area as bilateral dark stripes in midbrain slices on the acquired mp2rage T1 sequence and created a study-specific mask based on the landmarks in Bunzeck and Duzel using Mricron software ( (). The ventral striatum/pallidum ROI was similarly created and comprised the ventral anterior portion of the head and body of caudate, nucleus accumbens, ventral putamen and pallidum (). [...] We used DCM12 with SPM12 (v6225) to compute effective connectivity within the hippocampal–basal ganglia–midbrain loop. In DCM for fMRI, the dynamics of the neural states underlying regional BOLD responses are modelled by a bilinear differential equation that describes how the neural states change as a function of endogenous interregional connections, modulatory effects on these connections and driving inputs. The endogenous connections represent constant coupling strengths, whereas the modulatory effects represent context-specific and additive changes in coupling (task-induced alterations in connectivity). The modelled neuronal dynamic is then mapped to the measured BOLD signal using a hemodynamic forward model. In the current study, based on the group-level fMRI findings, we explicitly explored how the coupling strengths between hippocampus, ventral striatum/pallidum and midbrain were changed by reward-predicting cues (modulatory effect). […]

Pipeline specifications

Software tools MRIcron, SPM
Applications Magnetic resonance imaging, Functional magnetic resonance imaging
Organisms Homo sapiens
Chemicals Dopamine