Sub-millimeter fMRI reveals multiple topographical digit representations that form action maps in human motor cortex

The human brain coordinates a wide variety of motor activities. On a large scale, the cortical motor system is topographically organized such that neighboring body parts are represented by neighboring brain areas. This homunculus-like somatotopic organization along the central sulcus has been observed using neuroimaging for large body parts such as the face, hands and feet. However, on a finer scale, invasive electrical stimulation studies show deviations from this somatotopic organization that suggest an organizing principle based on motor actions rather than body part moved. It has not been clear how the action-map organization principle of the motor cortex in the mesoscopic (sub-millimeter) regime integrates into a body map organization principle on a macroscopic scale (cm). Here we developed and applied advanced mesoscopic (sub-millimeter) fMRI and analysis methodology to non-invasively investigate the functional organization topography across columnar and laminar structures in humans. Compared to previous methods, in this study, we could capture locally specific blood volume changes across entire brain regions along the cortical curvature. We find that individual fingers have multiple mirrored representations in the primary motor cortex depending on the movements they are involved in. We find that individual digits have cortical representations up to 3 ​mm apart from each other arranged in a column-like fashion. These representations are differentially engaged depending on whether the digits’ muscles are used for different motor actions such as flexion movements, like grasping a ball or retraction movements like releasing a ball. This research provides a starting point for non-invasive investigation of mesoscale topography across layers and columns of the human cortex and bridges the gap between invasive electrophysiological investigations and large coverage non-invasive neuroimaging

Methods for Fine Scale Functional Imaging of Tactile Motion in Human and Nonhuman Primates

In the visual and auditory systems specialized neural pathways use motion cues to track object motion and self-motion, and use differential motion cues for figure-ground segregation. To examine the neural circuits that encode motion in the somatosensory system, we have developed neuroimaging methods to study motion processing in human and nonhuman primates. We have implemented stimulus presentation paradigms to examine neural encoding of apparent motion percepts. These paradigms are designed to be compatible with fMRI, optical imaging, and electrophysiological methods, thereby permitting direct comparison of data derived across neurofunctional scales. An additional motivation for using a common tactile motion stimulation paradigm is to bridge two disparate bodies of work, that derived from neuroimaging studies in humans and another from neuroimaging, neurophysiological and neuroanatomical studies in monkeys. Here, we demonstrate that such an approach through the use of optical imaging and 9.4 Tesla fMRI experiments in monkeys, and 7 Tesla fMRI experiments in humans is effective in revealing neural regions activated by tactile motion stimuli. These methods span spatial scales capable of detecting 100 μm sized domains to those that would reveal global whole brain circuits. Armed with such capabilities, our long-term goals are to identify directionally selective areas and directionally se-lective functional domains and understand the global pathways within which they reside. Such knowledge would have great impact on our thinking regarding not only tactile motion processing, but also general strategies underlying somatosensory cortical processing

LayNii: a software suite for layer-fMRI

High-resolution fMRI in the sub-millimeter regime allows researchers to resolve brain activity across cortical layers and columns non-invasively. While these high-resolution data make it possible to address novel questions of directional information flow within and across brain circuits, the corresponding data analyses are challenged by MRI artifacts, including image blurring, image distortions, low SNR, and restricted coverage. These challenges often result in insufficient spatial accuracy of conventional analysis pipelines. Here we introduce a new software suite that is specifically designed for layer-specific functional MRI: LayNii. This toolbox is a collection of command-line executable programs written in C/C++ and is distributed opensource and as pre-compiled binaries for Linux, Windows, and macOS. LayNii is designed for layer-fMRI data that suffer from SNR and coverage constraints and thus cannot be straightforwardly analyzed in alternative software packages. Some of the most popular programs of LayNii contain ‘layerification’ and columnarization in the native voxel space of functional data as well as many other layer-fMRI specific analysis tasks: layer-specific smoothing, model-based vein mitigation of GE-BOLD data, quality assessment of artifact dominated sub-millimeter fMRI, as well as analyses of VASO data

Efficient high-resolution TMS mapping of the human motor cortex by nonlinear regression

Transcranial magnetic stimulation (TMS) is a powerful tool to investigate causal structure-function relationships in the human brain. However, a precise delineation of the effectively stimulated neuronal populations is notoriously impeded by the widespread and complex distribution of the induced electric field. Here, we propose a method that allows rapid and feasible cortical localization at the individual subject level. The functional relationship between electric field and behavioral effect is quantified by combining experimental data with numerically modeled fields to identify the cortical origin of the modulated effect. Motor evoked potentials (MEPs) from three finger muscles were recorded for a set of random stimulations around the primary motor area. All induced electric fields were nonlinearly regressed against the elicited MEPs to identify their cortical origin. We could distinguish cortical muscle representation with high spatial resolution and localized them primarily on the crowns and rims of the precentral gyrus. A post-hoc analysis revealed exponential convergence of the method with the number of stimulations, yielding a minimum of about 180 random stimulations to obtain stable results. Establishing a functional link between the modulated effect and the underlying mode of action, the induced electric field, is a fundamental step to fully exploit the potential of TMS. In contrast to previous approaches, the presented protocol is particularly easy to implement, fast to apply, and very robust due to the random coil positioning and therefore is suitable for practical and clinical applications

A dual larynx motor networks hypothesis

Humans are vocal modulators par excellence. This ability is supported in part by the dual representation of the laryngeal muscles in the motor cortex. Movement, however, is not the product of motor cortex alone but of a broader motor network. This network consists of brain regions that contain somatotopic maps that parallel the organization in motor cortex. We therefore present a novel hypothesis that the dual laryngeal representation is repeated throughout the broader motor network. In support of the hypothesis, we review existing literature that demonstrates the existence of network-wide somatotopy and present initial evidence for the hypothesis' plausibility. Understanding how this uniquely human phenotype in motor cortex interacts with broader brain networks is an important step toward understanding how humans evolved the ability to speak. We further suggest that this system may provide a means to study how individual components of the nervous system evolved within the context of neuronal networks. This article is part of the theme issue ‘Voice modulation: from origin and mechanism to social impact (Part I)’

Structure of population activity in primary motor cortex for single finger flexion and extension

Copyright © 2020 the authors How is the primary motor cortex (M1) organized to control fine finger movements? We investigated the population activity in M1 for single finger flexion and extension, using 7T functional magnetic resonance imaging (fMRI) in female and male human participants and compared these results to the neural spiking patterns recorded in two male monkeys performing the identical task. fMRI activity patterns were distinct for movements of different fingers, but were quite similar for flexion and extension of the same finger. In contrast, spiking patterns in monkeys were quite distinct for both fingers and directions, which is similar to what was found for muscular activity patterns. The discrepancy between fMRI and electrophysiological measurements can be explained by two (non-mutually exclusive) characteristics of the organization of finger flexion and extension movements. Given that fMRI reflects predominantly input and recurrent activity, the results can be explained by an architecture in which neural populations that control flexion or extension of the same finger produce distinct outputs, but interact tightly with each other and receive similar inputs. Additionally, neurons tuned to different movement directions for the same finger (or combination of fingers) may cluster closely together, while neurons that control different finger combinations may be more spatially separated. When measuring this organization with fMRI at a coarse spatial scale, the activity patterns for flexion and extension of the same finger would appear very similar. Overall, we suggest that the discrepancy between fMRI and electrophysiological measurements provides new insights into the general organization of fine finger movements in M1

Assessing the effective connectivity of premotor areas during real vs imagined grasping: a DCM-PEB approach

The parieto-frontal circuit underlying grasping, which requires the serial involvement of the anterior intraparietal area (aIPs) and the ventral premotor cortex (PMv), has been recently extended enlightening the role of the dorsal premotor cortex (PMd). The supplementary motor area (SMA) has been also suggested to encode grip force for grasping actions; furthermore, both PMd and SMA are known to play a crucial role in motor imagery. Here, we aimed at assessing the dynamic couplings between left aIPs, PMv, PMd, SMA and primary motor cortex (M1) by comparing executed and imagined right-hand grasping, using Dynamic Causal Modelling (DCM) and Parametrical Empirical Bayes (PEB) analyses. 24 subjects underwent an fMRI exam (3T) during which they were asked to perform or imagine a grasping movement visually cued by photographs of commonly used objects. We tested whether the two conditions a) exert a modulatory effect on both forward and feedback couplings among our areas of interest, and b) differ in terms of strength and sign of these parameters. Results of the real condition confirmed the serial involvement of aIPs, PMv and M1. PMv also exerted a positive influence on PMd and SMA, but received an inhibitory feedback only from PMd. Our results suggest that a general motor program for grasping is planned by the aIPs-PMv circuit; then, PMd and SMA encode high-level features of the movement. During imagery, the connection strength from aIPs to PMv was weaker and the information flow stopped in PMv; thus, a less complex motor program was planned. Moreover, results suggest that SMA and PMd cooperate to prevent motor execution. In conclusion, the comparison between execution and imagery reveals that during grasping premotor areas dynamically interplay in different ways, depending on task demands