The advancement of large-scale magnetic resonance imaging (MRI) studies has enabled systematic investigations of cortical morphology, such as cortical thickness and surface area, across a variety of psychiatric disorders. In particular, the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium has conducted some of the largest MRI studies characterizing group differences between patients (cases) and control individuals in the cerebral cortex for a number of disorders, including attention-deficit/hyperactivity disorder (ADHD),¹ autism spectrum disorder (ASD),² bipolar disorder (BD),³ major depressive disorder (MDD),⁴ obsessive-compulsive disorder (OCD),⁵ and schizophrenia.⁶ Nonetheless, the neurobiology underlying these MRI-derived macroscopic features is not well understood.

Age-related changes in mastication-induced brain neuronal activity have been suggested. However, in humans, little is known about the anatomical regions involved. Using fMRI during cycles of rhythmic gum-chewing and no chewing, we have examined the effect of aging on brain regional activity during chewing in young adult (19–26 yrs), middle-aged (42–55 yrs), and aged (65–73 yrs) healthy humans. In all subjects, chewing resulted in a bilateral increase in the BOLD signals in the sensorimotor cortex, cerebellum, thalamus, supplementary motor area, and insula, and a unilateral increase in the right prefrontal area. In the first three regions, the signal increases were attenuated in an age-dependent manner, whereas, in the right prefrontal area, the converse was seen. The remaining two regions showed no significant differences with ages. These results indicate that chewing causes regional increases in neuronal activity in the brain, some of which are age-dependent.

The specificity of the hemodynamic response function (HRF) is determined spatially by the vascular architecture and temporally by the evolution of hemodynamic changes. The stimulus duration has additional influence on the spatiotemporal evolution of the HRF, as brief stimuli elicit responses that engage only the local vasculature, whereas long stimuli lead to the involvement of remote vascular supply and drainage. Here, we used functional magnetic resonance imaging to investigate the spatiotemporal evolution of the blood oxygenation level-dependent (BOLD), cerebral blood flow (CBF), and cerebral blood volume (CBV) HRF to ultrashort forelimb stimulation in an anesthetized rodent model. The HRFs to a single 333-μs-long stimulus were robustly detected and consisted of a rapid response in both CBF and CBV, with an onset time (OT) of 350 ms and a full width at half-maximum of 1 s. In contrast, longer stimuli elicited a dispersive transit of oxygenated blood across the cortical microvasculature that significantly prolonged the evolution of the CBV HRF, but not the CBF. The CBF and CBV OTs suggest that vasoactive messengers are synthesized, released, and effective within 350 ms. However, the difference between the BOLD and CBV OT (∼100 ms) was significantly smaller than the arteriolar–venular transit time (∼500 ms), indicating an arterial contribution to the BOLD HRF. Finally, the rapid rate of growth of the active region with stimulus elongation suggests that functional hyperemia is an integrative process that involves the entire functional cortical depth. These findings offer a new view into the spatiotemporal dynamics of functional hemodynamic regulation in the brain.