Ultra-high field (7T) functional magnetic resonance imaging in amyotrophic lateral sclerosis: a pilot study

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the central nervous system that results in a progressive loss of motor function and ultimately death. It is critical, yet also challenging, to develop non-invasive biomarkers to identify, localize, measure and/or track biological mechanisms implicated in ALS. Such biomarkers may also provide clues to identify potential molecular targets for future therapeutic trials. Herein we report on a pilot study involving twelve participants with ALS and nine age-matched healthy controls who underwent high-resolution resting state functional magnetic resonance imaging at an ultra-high field of 7 Tesla. A group-level whole-brain analysis revealed a disruption in long-range functional connectivity between the superior sensorimotor cortex (in the precentral gyrus) and bilateral cerebellar lobule VI. Post hoc analyses using atlas-derived left and right cerebellar lobule VI revealed decreased functional connectivity in ALS participants that predominantly mapped to bilateral postcentral and precentral gyri. Cerebellar lobule VI is a transition zone between anterior motor networks and posterior non-motor networks in the cerebellum, and is associated with a wide range of key functions including complex motor and cognitive processing tasks. Our observation of the involvement of cerebellar lobule VI adds to the growing number of studies implicating the cerebellum in ALS. Future avenues of scientific investigation should consider how high-resolution imaging at 7T may be leveraged to visualize differences in functional connectivity disturbances in various genotypes and phenotypes of ALS along the ALS-frontotemporal dementia spectrum.

Keywords: 7 Tesla; Amyotrophic lateral sclerosis; Cerebellum; Functional magnetic resonance imaging; Ultra-high field.

Fig. 1

Decreased functional connectivity between the sensorimotor cortex and bilateral lobule VI of the cerebellum visualized via the functional contrast Controls $>$ ALS participants ($p<0.005$ uncorrected, two-sided; cluster threshold: $p<0.05$ with false discovery rate correction) for a seed region located in the superior sensorimotor cortex (MNI coordinates = (0, –31, 67)). The results are presented as a) an overlay onto a single 2D axial slice through the cerebellum, and b) a projection onto a cerebellar flatmap (Diedrichsen and Zotow, 2015).

Fig. 2

Visualization of the post hoc seed-to-voxel contrast Controls $>$ ALS participants using atlas-derived a) left, b) right, and c) bilateral cerebellar lobule VI as seed regions. Group-level differences ($p<0.001$ uncorrected, two-sided; cluster threshold: $p<0.05$ with false discovery rate correction) were predominantly observed in the postcentral and precentral gyri. The complete list of clusters is presented in Table S1.