The laminar pattern of proprioceptive activation in human primary motor cortex

Abstract

The primary motor cortex (M1) has traditionally been viewed as a motor output generator. However, its vital role in proprioceptive somatosensation is increasingly being recognized. Yet, our understanding of proprioceptive somatosensation in M1 at the laminar scale is limited, largely due to methodological challenges. Empirical findings in primates and rodents suggest a pronounced role of superficial cortical layers, but the involvement of deep layers has yet to be examined in humans. Submillimeter resolution fMRI has emerged in recent years, paving the way for the study of layer-dependent activity in humans (laminar fMRI). In the present study, laminar fMRI was employed to investigate the laminar pattern of proprioceptive somatosensation on M1 deep layer activation using passive finger movements as proprioceptive stimulation. Significant M1 deep layer activation was observed in response to proprioceptive stimulation across 10 healthy subjects using vascular space occupancy (VASO) at 7T. For further validation, two additional subjects were scanned using a balanced steady-state free precession (bSSFP) sequence with ultrahigh (0.3 mm) in-plane resolution, yielding converging results. These results were interpreted in the light of previous laminar fMRI studies and the active inference account of motor control. We suggest that a considerable proportion of M1 deep layer activation is due to proprioceptive influence and that deep layers of M1 constitute a key component in proprioceptive circuits.

Laminar fMRI in the locked-in stage of amyotrophic lateral sclerosis shows preserved activity in layer Vb of primary motor cortex

“…Input information is believed to be pre-processed via recurrent activation in superficial layers before being relayed to deep layers to inform motor output (rings and arrows) 16,17 . Recent laminar fMRI studies in healthy subjects support a similar model in humans 6,[18][19][20][21] .…”

“…In line with known input/output organisation of M1 (Fig. 1A) and co-localisation with layer Vb, the deep layer peak is widely believed to mainly reflect corticospinal motor output emerging from UMNs 2,6,[18][19][20][21]41,42 . This interpretation is compatible with empirical evidence that activation is confined mainly to superficial layers in tasks presumably devoid of corticospinal output, including tactile stimulation (somatosensory input) 18,20 and motor imagery (motor input) 6,19 .…”

“…Input information is believed to be pre-processed via recurrent activation in superficial layers before being relayed to deep layers to inform motor output (rings and arrows) 16,17 . Recent laminar fMRI studies in healthy subjects support a similar model in humans 6,18–21 . UMNs (layer Vb) and LMNs (spinal cord) are the cardinal cells affected by ALS ( B ) Overview of patient characteristics (details provided in Materials and Methods), and illustration of the procedures to overcome challenges of scanning a locked-in stage ALS patient.…”

“…Since somatosensation is relatively unaffected in ALS 1 , both M1 and S1 were expected to activate during passive movements as in healthy subjects 21,27,28 . Blood oxygen leveldependent (BOLD) fMRI at 0.82 mm isotropic resolution was employed to evaluate cortical activation during these tasks (Fig.…”

“…S1) and may reflect proprioceptive context delivered from superficial to deep layers to guide impending motor output. Alternatively, it may reflect corticospinal drive being present even during passive movements (discussed in detail in 21 ). Regardless, afferent proprioceptive inputs could not have affected the deep layer signal during attempted movements in the patient, as the finger was not overtly moving.…”