Whole-Brain Functional Network Connectivity Abnormalities in Affective and Non-Affective Early Phase Psychosis

Abstract

Psychosis disorders share overlapping symptoms and are characterized by a wide-spread breakdown in functional brain integration. Although neuroimaging studies have identified numerous connectivity abnormalities in affective and non-affective psychoses, whether they have specific or unique connectivity abnormalities, especially within the early stage is still poorly understood. The early phase of psychosis is a critical period with fewer chronic confounds and when treatment intervention may be most effective. In this work, we examined whole-brain functional network connectivity (FNC) from both static and dynamic perspectives in patients with affective psychosis (PAP) or with non-affective psychosis (PnAP) and healthy controls (HCs). A fully automated independent component analysis (ICA) pipeline called “Neuromark” was applied to high-quality functional magnetic resonance imaging (fMRI) data with 113 early-phase psychosis patients (32 PAP and 81 PnAP) and 52 HCs. Relative to the HCs, both psychosis groups showed common abnormalities in static FNC (sFNC) between the thalamus and sensorimotor domain, and between subcortical regions and the cerebellum. PAP had specifically decreased sFNC between the superior temporal gyrus and the paracentral lobule, and between the cerebellum and the middle temporal gyrus/inferior parietal lobule. On the other hand, PnAP showed increased sFNC between the fusiform gyrus and the superior medial frontal gyrus. Dynamic FNC (dFNC) was investigated using a combination of a sliding window approach, clustering analysis, and graph analysis. Three reoccurring brain states were identified, among which both psychosis groups had fewer occurrences in one antagonism state (state 2) and showed decreased network efficiency within an intermediate state (state 1). Compared with HCs and PnAP, PAP also showed a significantly increased number of state transitions, indicating more unstable brain connections in affective psychosis. We further found that the identified connectivity features were associated with the overall positive and negative syndrome scale, an assessment instrument for general psychopathology and positive symptoms. Our findings support the view that subcortical-cortical information processing is disrupted within five years of the initial onset of psychosis and provide new evidence that abnormalities in both static and dynamic connectivity consist of shared and unique features for the early affective and non-affective psychoses.

Metastability as a neuromechanistic biomarker of schizophrenia pathology

“…However, static FC relies on statistical relationships between fMRI signals throughout the complete scan, which forces it to discard critical information about the brain's dynamics. In contrast, it is reasonable to believe that dynamic approaches -which consider the temporal dynamics of fMRI signalsmay have the potential to discover more precise and informative biomarkers [16][17][18][19][20][21][22][23][24][25][26][27][28][29].…”

Machine Learning Predicts Treatment Response in Bipolar & Major Depressive Disorders

“…2 presents a composite view of the neuromark templates. The neuromark templates have been successfully applied in numerous studies and have been validated as robust spatial priors that provide reliable functional network features across subjects and datasets (Fu et al, 2021c,b,a).…”

Visual system assessment for predicting a transition to psychosis

“…B Similar hyperconnectivity patterns have been observed in CHR patients who convert versus those who do not convert to a psychotic disorder (Adapated with permission from [ 61 ]). C Different investigators have found comparable patterns (after FDR correction) in early-stage non-affective psychosis patients relative to HCs, with one-third of the visual nodes being hyperconnected to the thalamic node (Adapted with permission from [ 60 ]). D Briefly flashed checkered images have elicited a muted P1 amplitude in FEPs relative to HCs (Adapted with permission from [ 65 ]).…”

“…Such hyperconnectivity has been also shown by other investigators (90 HCs, 90 SZs) [ 58 ] and may be partly explained by weaker anatomical connections between these same areas [ 59 ]. Thalamo-cortical visual functional hyperconnectivity has also been documented in affective and non-affective psychosis patients within 5 years of their first psychotic episode, when compared to healthy controls ( n = 32, 81, 52, respectively) [ 60 ]. Finally, CHR patients who converted to a psychotic disorder ( n = 21) displayed more visual thalamo-cortical connectivity at baseline than those who did not convert ( n = 222) (Fig.…”

“…Therefore, our tests may not be as useful in ordinary clinical contexts, where a transition to any psychotic disorder remains the question of interest. First, it is simply too soon to decide whether the above-described assessments are useless for flagging other forms of psychosis and, indeed, some have already differentiated individuals with affective early psychosis [ 60 ]. Second, if the above-mentioned tests primarily differentiate non-affective psychosis patients, then that itself would be important; it would demonstrate novel biological and behavioral differences between patient subtypes that could justify a search for more individualized treatments and interventions.…”