Focal Pontine Lesions Provide Evidence That Intrinsic Functional Connectivity Reflects Polysynaptic Anatomical Pathways

Abstract

Intrinsic functional connectivity detected by functional MRI (fMRI) provides a useful but indirect approach to study the organization of human brain systems. An unresolved question is whether functional connectivity measured by resting state fMRI reflects anatomical connections. In this study we used the well-characterized anatomy of cerebrocerebellar circuits to directly test whether intrinsic functional connectivity is associated with an anatomic pathway. Eleven first episode stoke patients were scanned five times during a period of six months and eleven healthy control subjects were scanned three times within one month. In patients with right pontine stokes, the functional connectivity between the right motor cortex and the left cerebellum was selectively reduced. This connectivity pattern was reversed in patients with left pontine strokes. While factors beyond anatomical connectivity contribute to fMRI measures of functional correlation, these results provide direct evidence that functional connectivity depends upon intact connections within a specific polysynaptic pathway.

Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases

“…Here we focus on rs-fcMRI for both theoretical and practical reasons. From the theoretical standpoint, interactions observed with rs-fcMRI are sensitive to the influence of polysynaptic connectivity (40,41,91,92). This sensitivity allows the identification of distant and complex network interactions that match well with data suggesting that the effects of brain stimulation are also polysynaptic (4,10,(26)(27)(28)(29)(30)(31)(32)(33).…”

Measuring Cortical Connectivity in Alzheimer’s Disease as a Brain Neural Network Pathology: Toward Clinical Applications

“…The rs-fMRI signal is of special relevance for many analytical methods assessing functional connectivity. It provides spontaneous low-frequency fluctuations of blood oxygen level-dependent (BOLD) signals (Figure 1) and makes possible investigations of the network architecture of brain systems (Biswal, Yetkin, Haughton, & Hyde, 1995;Biswal et al, 2010;Fox & Raichle, 2007;Lu et al, 2011). Compared to conventional fMRI studies, rs-fMRI is a task-free and data-driven neuroimaging technique that can be easily acquired in cognitively impaired populations.…”

Studying Brain Organization via Spontaneous fMRI Signal

“…An additional example is found in the cerebellum, which displays correlated activity with cortical regions that are separated from the cerebellum by several synapses (Krienen and Buckner, 2009). Lesions at the mediating synapses, for example in the pons, perturb corticocerebellar correlations in predictable ways (Lu et al, 2011). The observed correlation between any two regions likely reflects weighted representation of many or all possible pathways between those regions, many of them mediated by other brain regions (Adachi et al, 2012).…”