Distinct functional and structural connectivity of the human hand-knob supported by intraoperative findings

Abstract

Fine motor skills rely on the control of hand muscles exerted by a region of primary motor cortex (M1) that has been extensively investigated in monkeys. Although neuroimaging enables the exploration of this system also in humans, indirect measurements of brain activity prevent causal definitions of hand motor representations, which can be achieved using data obtained during brain mapping in tumor patients. High frequency direct electrical stimulation delivered at rest (HF DES-Rest) on the hand-knob region of the precentral gyrus has identified two sectors showing differences in cortical excitability. Using quantitative analysis of motor output elicited with HF DES-Rest we characterised two sectors based on their excitability, higher in the posterior and lower in the anterior sector. We studied whether the different cortical excitability of these two regions reflected differences in functional and structural connectivity. Using healthy adults from the Human Connectome Project, we computed functional and structural connectivity of the anterior and the posterior hand-knob sectors identified within a large cohort of patients. The comparison of functional connectivity of the two seeds showed that the anterior hand-knob, relative to the posterior hand-knob, showed stronger functional connections with a bilateral set of parieto-frontal areas responsible for integrating perceptual and cognitive hand-related sensorimotor processes necessary for goal-related actions. This was reflected in different patterns of structural connectivity between the two sectors. Our results suggest that the human hand-knob is a functionally and structurally heterogeneous region organized along a motor-cognitive gradient.

SIGNIFICANCE STATEMENT:

The capability to perform complex manipulative tasks is one of the major characteristics of primates and relies on the fine control of hand muscles exerted by a highly specialized region of the precentral gyrus, often termed the ‘hand-knob’ sector. Using intraoperative brain mapping, we identify two ‘hand-knob’ sectors (posterior and anterior) characterized by differences in cortical excitability. Based on resting-state functional connectivity and tractography in healthy subjects, we show that posterior and anterior hand-knob sectors differ in their functional and structural connectivity with fronto-parietal regions. Thus, antero-posterior differences in cortical excitability are paralleled by differences in functional and structural connectivity that likely reflect a motor (posterior) to cognitive (anterior) organization of this cortical region.