These data show that a calorie-restricted KD enhances brain metabolism. We propose an anticonvulsant mechanism of the KD involving mitochondrial biogenesis leading to enhanced alternative energy stores.

Accruing data suggest that oxidative stress may be a factor underlying the pathophysiology of bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ). Glutathione (GSH) is the major free radical scavenger in the brain. Diminished GSH levels elevate cellular vulnerability towards oxidative stress; characterized by accumulating reactive oxygen species. The aim of this study was to determine if mood disorders and SCZ are associated with abnormal GSH and its functionally related enzymes. Post-mortem prefrontal cortex from patients with BD, MDD, SCZ, and from non-psychiatric comparison controls were provided by the Stanley Foundation Neuropathology Consortium. Spectrophotometric analysis was utilized for the quantitative determination of GSH, while immunoblotting analyses were used to examine expression of glutamyl-cysteine ligase (GCL), GSH reductase (GR), and GSH peroxidase (GPx). We found that the levels of reduced, oxidized, and total GSH were significantly decreased in all psychiatric conditions compared to the control group. Although GCL and GR levels did not differ between groups, the levels of GPx were reduced in MDD and SCZ compared to control subjects. Since oxidative damage has been demonstrated in MDD, BD, and SCZ, our finding that GSH levels are reduced in post-mortem prefrontal cortex suggests that these patient groups may be more susceptible to oxidative stress.

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that allows for visualization of activated brain regions. Until recently, fMRI studies have focused on gray matter. There are two main reasons white matter fMRI remains controversial: (1) the blood oxygen level dependent (BOLD) fMRI signal depends on cerebral blood flow and volume, which are lower in white matter than gray matter and (2) fMRI signal has been associated with post-synaptic potentials (mainly localized in gray matter) as opposed to action potentials (the primary type of neural activity in white matter). Despite these observations, there is no direct evidence against measuring fMRI activation in white matter and reports of fMRI activation in white matter continue to increase. The questions underlying white matter fMRI activation are important. White matter fMRI activation has the potential to greatly expand the breadth of brain connectivity research, as well as improve the assessment and diagnosis of white matter and connectivity disorders. The current review provides an overview of the motivation to investigate white matter fMRI activation, as well as the published evidence of this phenomenon. We speculate on possible neurophysiologic bases of white matter fMRI signals, and discuss potential explanations for why reports of white matter fMRI activation are relatively scarce. We end with a discussion of future basic and clinical research directions in the study of white matter fMRI.

Although blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) is a widely available, non-invasive technique that offers excellent spatial resolution, it remains limited by practical constraints imposed by the scanner environment. More recently, functional near infrared spectroscopy (fNIRS) has emerged as an alternative hemodynamic-based approach that possesses a number of strengths where fMRI is limited, most notably in portability and higher tolerance for motion. To date, fNIRS has shown promise in its ability to shed light on the functioning of the human brain in populations and contexts previously inaccessible to fMRI. Notable contributions include infant neuroimaging studies and studies examining full-body behaviors, such as exercise. However, much like fMRI, fNIRS has technical constraints that have limited its application to clinical settings, including a lower spatial resolution and limited depth of recording. Thus, by combining fMRI and fNIRS in such a way that the two methods complement each other, a multimodal imaging approach may allow for more complex research paradigms than is feasible with either technique alone. In light of these issues, the purpose of the current review is to: (1) provide an overview of fMRI and fNIRS and their associated strengths and limitations; (2) review existing combined fMRI-fNIRS recording studies; and (3) discuss how their combined use in future research practices may aid in advancing modern investigations of human brain function.

Results suggest that MT is a feasible early intervention in persons with SCD. Longer-term follow-up with larger sample sizes will determine whether MT can slow the rate of decline in persons who may be at risk for Alzheimer's dementia.