The relative brain signal variability increases in the behavioral variant of frontotemporal dementia and Alzheimer's disease but not in schizophrenia.

Overlapping symptoms between Alzheimer's disease (AD), behavioral variant of frontotemporal dementia (bvFTD), and schizophrenia (SZ) can lead to misdiagnosis and delays in appropriate treatment, especially in cases of early-onset dementia. To determine the potential of brain signal variability as a diagnostic tool, we assessed the coefficient of variation of the BOLD signal (CVBOLD) in 234 participants spanning bvFTD (n = 53), AD (n = 17), SZ (n = 23), and controls (n = 141). All underwent functional and structural MRI scans. Data unveiled a notable increase in CVBOLD in bvFTD patients across both datasets (local and international, p < 0.05), revealing an association with clinical scores (CDR and MMSE, r = 0.46 and r = -0.48, p < 0.0001). While SZ and control group demonstrated no significant differences, a comparative analysis between AD and bvFTD patients spotlighted elevated CVBOLD in the frontopolar cortices for the latter (p < 0.05). Furthermore, CVBOLD not only presented excellent diagnostic accuracy for bvFTD (AUC 0.78-0.95) but also showcased longitudinal repeatability. During a one-year follow-up, the CVBOLD levels increased by an average of 35% in the bvFTD group, compared to a 2% increase in the control group (p < 0.05). Our findings suggest that CVBOLD holds promise as a biomarker for bvFTD, offering potential for monitoring disease progression and differentiating bvFTD from AD and SZ.

Symptomatic psychosis risk and physiological fluctuation in functional MRI data.

BACKGROUND: Physiological brain pulsations have been shown to play a critical role in maintaining interstitial homeostasis in the glymphatic brain clearance mechanism. We investigated whether psychotic symptomatology is related to the physiological variation of the human brain using fMRI. METHODS: The participants (N = 277) were from the Northern Finland Birth Cohort 1986. Psychotic symptoms were evaluated with the Positive Symptoms Scale of the Structured Interview for Prodromal Syndromes (SIPS). We used the coefficient of variation of BOLD signal (CVBOLD) as a proxy for physiological brain pulsatility. The CVBOLD-analyses were controlled for motion, age, sex, and educational level. The results were also compared with fMRI and voxel-based morphometry (VBM) meta-analyses of schizophrenia patients (data from the Brainmap database). RESULTS: At the global level, participants with psychotic-like symptoms had higher CVBOLD in cerebrospinal fluid (CSF) and white matter (WM), when compared to participants with no psychotic symptoms. Voxel-wise analyses revealed that CVBOLD was increased, especially in periventricular white matter, basal ganglia, cerebellum and parts of the cortical structures. Those brain regions, which included alterations of physiological fluctuation in symptomatic psychosis risk, overlapped <6% with the regions that were found to be affected in the meta-analyses of previous fMRI and VBM studies in schizophrenia patients. Motion did not vary as a function of SIPS. CONCLUSIONS: Psychotic-like symptoms were associated with elevated CVBOLD in a variety of brain regions. The CVBOLD findings may produce new information about cerebral physiological fluctuations that have been out of reach in previous fMRI and VBM studies.