Insulin, a vasoactive modulator regulating peripheral and cerebral blood flow, has been consistently linked to aging and longevity. In this proof of principle study, using a randomized, double-blinded, placebo-controlled crossover design, we explored the effects of intranasally administered insulin (40IU) on cerebral blood flow (CBF) and perfusion in older (60-69 years, n=11) and younger (20-26 years, n=8) adults. Changes in CBF through the major cerebropetal arteries were assessed via phase contrast MR-angiography, and regional cortical tissue perfusion via pseudo-continuous arterial spin labelling. Total flow through the major cerebropetal arteries was unchanged in both young and old. In the older participants, intranasal insulin compared to placebo increased perfusion through the occipital gray matter (65.2±11.0 mL/100g/min vs 61.2±10.1 mL/100g/min, P=0.001), and in the thalamus (68.28±6.75 mL/100g/min versus 63.31±6.84 mL/100g/min, P=0.003). Thus, intranasal insulin improved tissue perfusion of the occipital cortical brain region and the thalamus in older adults.

To study cerebral metabolism in neonates after unilateral cerebral infarcts 4 neonates (3 full-terms, one preterm with a gestational age of 35 weeks) with unilateral cerebral infarcts were examined at 7 to 49 days of postnatal age, using proton magnetic resonance spectroscopic imaging (1H-MRSI). Three neonates had infarcts of the left middle cerebral artery (MCA), one had a right posterior cerebral artery infarct and a more localized anterior lesion. Examinations were repeated in the three fullterm infants aged 2-3 months. Lactate resonances, which are not present in normal brain after term age, were demonstrated in two patients tested at 7 and 10 days of age respectively, and in one of them lactate was still present at two months. In all four neonates a decrease of the N-acetylaspartate/choline (NAA/Cho) ratio was seen within the area of infarction. Repeated MRS of two infants at three months showed an increase in NAA/Cho ratios in all brain areas, but values remained below normal in the infarcts. In the third infant a further decrease in the NAA/Cho ratio was demonstrated in the area of infarction at two months. The NAA/Cho ratios in the surrounding and contralateral brain tissue were normal in all infants. All three infants with a MCA infarct developed a hemiplegia. The aforementioned metabolic alterations in neonates with cerebral infarcts, demonstrated using 1H-MRSI, were found to be confined to the area of infarction and abnormalities persisted beyond the neonatal period.

Structural covariance networks are able to identify functionally organized brain regions by gray matter volume covariance. In Parkinson’s disease, the posterior cingulate network and anterior cingulate network showed decreased gray matter and therefore we examined the underlying molecular processes of these anatomical networks in the healthy brain. Whole brain transcriptomics from post-mortem samples from healthy adults, revealed upregulation of genes associated with serotonin, GPCR, GABA, glutamate, and RAS signaling pathways in these PD-related regions. Our results also suggest involvement of the cholinergic circuit, in which genes NPPA, SOSTDC1, and TYRP1 may play a protective role. Furthermore, both networks were associated with memory and neuropsychiatric disorders that overlap with Parkinson’s disease symptoms. The identified genes and pathways contribute to healthy functions of the posterior and anterior cingulate networks and disruptions to these functions may in turn contribute to the pathological and clinical events observed in Parkinson’s disease.

Huntington's disease (HD) is a devastating neurodegenerative disease affecting the brain resulting in neuronal dysfunction and neuronal loss. Since the identification of the gene responsible for HD, genetic testing has become widely available, allowing for genetic status of persons at risk for HD to be determined. For the effective evaluation of future therapeutic trials a great need exists for sensitive biomarkers. In (premanifest) HD, MRI of the brain is one of the most logical candidates as a biomarker, as opposed to clinical measures, since brain neurons are the main target of the disease. These biomarkers can facilitate early detection of disease related changes, but are also needed to monitor disease progression from the premanifest phase of HD onwards. MRI derived parameters have this biomarker potential as they have been shown to identify brain abnormalities before symptom onset. In this review the available MRI techniques of conventional MRI, Diffusion Tensor Imaging, Magnetization Transfer Imaging, Magnetic Resonance Spectroscopy and Functional MRI will be discussed and the findings will be placed into context of different HD stages.