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Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 μV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery.

Characterizing the variability of resting-state functional brain connectivity across subjects and/or over time has recently attracted much attention. Principal component analysis (PCA) serves as a fundamental statistical technique for such analyses. However, performing PCA on high-dimensional connectivity matrices yields complicated "eigenconnectivity" patterns, for which systematic interpretation is a challenging issue. Here, we overcome this issue with a novel constrained PCA method for connectivity matrices by extending the idea of the previously proposed orthogonal connectivity factorization method. Our new method, modular connectivity factorization (MCF), explicitly introduces the modularity of brain networks as a parametric constraint on eigenconnectivity matrices. In particular, MCF analyzes the variability in both intra- and inter-module connectivities, simultaneously finding network modules in a principled, data-driven manner. The parametric constraint provides a compact module-based visualization scheme with which the result can be intuitively interpreted. We develop an optimization algorithm to solve the constrained PCA problem and validate our method in simulation studies and with a resting-state functional connectivity MRI dataset of 986 subjects. The results show that the proposed MCF method successfully reveals the underlying modular eigenconnectivity patterns in more general situations and is a promising alternative to existing methods.

Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999-2001 at the age of 33-35 years. A follow-up was conducted 9 years later during 2008-2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.

Spontaneous brain activity or off-line activity after memory encoding is associated with memory consolidation. A few recent resting-state functional magnetic resonance imaging (RS-fMRI) studies indicate that the RS-fMRI could map off-line memory consolidation effects. However, the gene effects on memory consolidation process remain largely unknown. Here we collected two RS-fMRI sessions, one before and another after an episodic memory encoding task, from two groups of healthy young adults, one with apolipoprotein E (APOE) ε2/ε3 and the other with APOE ε3/ε4. The ratio of regional homogeneity (ReHo), a measure of local synchronization of spontaneous RS-fMRI signal, of the two sessions was used as an index of memory-consolidation. APOE ε3/ε4 group showed greater ReHo ratio within the medial temporal lobe (MTL). The ReHo ratio in MTL was significantly correlated with the recognition memory performance in the APOE ε3/ε4 group but not in ε2/ε3 group. Additionally, APOE ε3/ε4 group showed lower ReHo ratio in the occipital and parietal picture-encoding areas. Our results indicate that APOE ε3/ε4 group may have a different off-line memory consolidation process compared to ε2/ε3 group. These results may help generate future hypotheses that the off-line memory consolidation might be impaired in Alzheimer's disease.