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A mind-body interface alternates with effector-specific regions in motor cortex
Authors
Evan M. Gordon,Roselyne J. Chauvin
Andrew N. Van,Aishwarya Rajesh,Ashley Nielsen,Dillan J. Newbold,Charles J. Lynch,Nicole A. Seider,Samuel R. Krimmel,Kristen M. Scheidter,Julia Monk,Ryland L. Miller,Athanasia Metoki,David F. Montez,Annie Zheng,Immanuel Elbau,Thomas Madison,Tomoyuki Nishino,Michael J. Myers,Sydney Kaplan,Carolina Badke D’Andrea,Damion V. Demeter,Matthew Feigelis,Deanna M. Barch,Christopher D. Smyser,Cynthia E. Rogers,Jan Zimmermann,Kelly N. Botteron,John R. Pruett,Jon T. Willie,Peter Brunner,Joshua S. Shimony,Benjamin P. Kay,Scott Marek,Scott A. Norris,Caterina Gratton,Chad M. Sylvester,Jonathan D. Power,Conor Liston,Deanna J. Greene,Jarod L. Roland,Steven E. Petersen,Marcus E. Raichle,Timothy O. Laumann,Damien A. Fair,Nico U.F. Dosenbach,Evan Gordon,Roselyne Chauvin,Andrew Van,Michael Myers,Timothy Laumann,Dillan Newbold,Charles Lynch,Nicole Seider,Samuel Krimmel,Kristen Scheidter,Ruth Miller,David Montez,Carolina D’Andrea,Damion Demeter,Deanna Barch,Christopher Smyser,Cynthia Rogers,Kelly Botteron,John Pruett,Jon Willie,Joshua Shimony,Benjamin Kay,Scott Norris,Chad Sylvester,Jonathan Power,Deanna Greene,Jarod Roland,Steven Petersen,Marcus Raichle,Damien Fair
+74 authors
,Nico DosenbachPublished
Oct 28, 2022
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A mind-body interface alternates with effector-specific regions in motor cortex
Evan M. Gordon1, Roselyne J. Chauvin2, Andrew N. Van2,3, Aishwarya Rajesh1, Ashley
Nielsen2, Dillan J. Newbold2,4, Charles J. Lynch5, Nicole A. Seider2,6, Samuel R. Krimmel2,
Kristen M. Scheidter2, Julia Monk2, Ryland L. Miller2,6, Athanasia Metoki2, David F. Montez2,
Annie Zheng2, Immanuel Elbau5, Thomas Madison7, Tomoyuki Nishino6, Michael J. Myers6,
Sydney Kaplan2, Carolina Badke D’Andrea1,6,8, Damion V. Demeter8, Matthew Feigelis8, Deanna
M. Barch1,6,9, Christopher D. Smyser1,2,10, Cynthia E. Rogers5,10, Jan Zimmermann11, Kelly N.
Botteron6, John R. Pruett6, Jon T. Willie2,5,12, Peter Brunner3,12, Joshua S. Shimony1, Benjamin
P. Kay2, Scott Marek1, Scott A. Norris1,2, Caterina Gratton13, Chad M. Sylvester6, Jonathan D.
Power5, Conor Liston5, Deanna J. Greene8, Jarod L. Roland12, Steven E. Petersen1,2,3,9,14,
Marcus E. Raichle1,2,3,9,14, Timothy O. Laumann6, Damien A. Fair7,15, Nico U.F.
Dosenbach1,2,3,9,10,16
1Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO,
63110, USA
2Department of Neurology, Washington University School of Medicine, St. Louis, MO, 63110,
USA
3Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO,
63130, USA
4Department of Neurology, New York University Langone Medical Center, New York, NY 10016,
USA
5Department of Psychiatry, Weill Cornell Medicine, New York, NY, 10021, USA
6Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110,
USA
7Department of Pediatrics, University of Minnesota, Minneapolis, MN, 55454, USA
8Department of Cognitive Science, University of California San Diego, La Jolla, CA 92093
9Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis,
MO, 63130, USA
10Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, 63110,
USA
11Department of Neuroscience, University of Minnesota, Minneapolis, MN, 55454, USA
12Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO,
63110, USA
13Department of Psychology, Florida State University, Tallahassee, FL, 32306, USA
14Department of Neuroscience, Washington University School of Medicine, St. Louis, MO,
63110, USA
15Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, 55454,
USA
16Program in Occupational Therapy, Washington University in St. Louis, St. Louis, MO, 63130,
USA
.CC-BY-NC-ND 4.0 International licenseavailable under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
The copyright holder for this preprintthis version posted October 28, 2022.;https://doi.org/10.1101/2022.10.26.513940doi:bioRxiv preprint
Evan M. Gordon1, Roselyne J. Chauvin2, Andrew N. Van2,3, Aishwarya Rajesh1, Ashley
Nielsen2, Dillan J. Newbold2,4, Charles J. Lynch5, Nicole A. Seider2,6, Samuel R. Krimmel2,
Kristen M. Scheidter2, Julia Monk2, Ryland L. Miller2,6, Athanasia Metoki2, David F. Montez2,
Annie Zheng2, Immanuel Elbau5, Thomas Madison7, Tomoyuki Nishino6, Michael J. Myers6,
Sydney Kaplan2, Carolina Badke D’Andrea1,6,8, Damion V. Demeter8, Matthew Feigelis8, Deanna
M. Barch1,6,9, Christopher D. Smyser1,2,10, Cynthia E. Rogers5,10, Jan Zimmermann11, Kelly N.
Botteron6, John R. Pruett6, Jon T. Willie2,5,12, Peter Brunner3,12, Joshua S. Shimony1, Benjamin
P. Kay2, Scott Marek1, Scott A. Norris1,2, Caterina Gratton13, Chad M. Sylvester6, Jonathan D.
Power5, Conor Liston5, Deanna J. Greene8, Jarod L. Roland12, Steven E. Petersen1,2,3,9,14,
Marcus E. Raichle1,2,3,9,14, Timothy O. Laumann6, Damien A. Fair7,15, Nico U.F.
Dosenbach1,2,3,9,10,16
1Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO,
63110, USA
2Department of Neurology, Washington University School of Medicine, St. Louis, MO, 63110,
USA
3Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO,
63130, USA
4Department of Neurology, New York University Langone Medical Center, New York, NY 10016,
USA
5Department of Psychiatry, Weill Cornell Medicine, New York, NY, 10021, USA
6Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110,
USA
7Department of Pediatrics, University of Minnesota, Minneapolis, MN, 55454, USA
8Department of Cognitive Science, University of California San Diego, La Jolla, CA 92093
9Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis,
MO, 63130, USA
10Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, 63110,
USA
11Department of Neuroscience, University of Minnesota, Minneapolis, MN, 55454, USA
12Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO,
63110, USA
13Department of Psychology, Florida State University, Tallahassee, FL, 32306, USA
14Department of Neuroscience, Washington University School of Medicine, St. Louis, MO,
63110, USA
15Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, 55454,
USA
16Program in Occupational Therapy, Washington University in St. Louis, St. Louis, MO, 63130,
USA
.CC-BY-NC-ND 4.0 International licenseavailable under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
The copyright holder for this preprintthis version posted October 28, 2022.;https://doi.org/10.1101/2022.10.26.513940doi:bioRxiv preprint
SUMMARY
Primary motor cortex (M1) has been thought to form a continuous somatotopic homunculus
extending down precentral gyrus from foot to face representations1,2. The motor homunculus
has remained a textbook pillar of functional neuroanatomy, despite evidence for concentric
functional zones3 and maps of complex actions4. Using our highest precision functional
magnetic resonance imaging (fMRI) data and methods, we discovered that the classic
homunculus is interrupted by regions with sharpy distinct connectivity, structure, and function,
alternating with effector-specific (foot, hand, mouth) areas. These inter-effector regions exhibit
decreased cortical thickness and strong functional connectivity to each other, and to prefrontal,
insular, and subcortical regions of the Cingulo-opercular network (CON), critical for executive
action5 and physiological control6, arousal7, and processing of errors8 and pain9. This inter-
digitation of action control-linked and motor effector regions was independently verified in the
three largest fMRI datasets. Macaque and pediatric (newborn, infant, child) precision fMRI
revealed potential cross-species analogues and developmental precursors of the inter-effector
system. An extensive battery of motor and action fMRI tasks documented concentric
somatotopies for each effector, separated by the CON-linked inter-effector regions. The inter-
effector regions lacked movement specificity and co-activated during action planning
(coordination of hands and feet), and axial body movement (e.g., abdomen, eyebrows). These
results, together with prior work demonstrating stimulation-evoked complex actions4 and
connectivity to internal organs (e.g., adrenal medulla)10, suggest that M1 is punctuated by an
integrative system for implementing whole-body action plans. Thus, two parallel systems
intertwine in motor cortex to form an integrate-isolate pattern: effector-specific regions (foot,
hand, mouth) for isolating fine motor control, and a mind-body interface (MBI) for the integrative
whole-organism coordination of goals, physiology, and body movement.
.CC-BY-NC-ND 4.0 International licenseavailable under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
The copyright holder for this preprintthis version posted October 28, 2022.;https://doi.org/10.1101/2022.10.26.513940doi:bioRxiv preprint
Primary motor cortex (M1) has been thought to form a continuous somatotopic homunculus
extending down precentral gyrus from foot to face representations1,2. The motor homunculus
has remained a textbook pillar of functional neuroanatomy, despite evidence for concentric
functional zones3 and maps of complex actions4. Using our highest precision functional
magnetic resonance imaging (fMRI) data and methods, we discovered that the classic
homunculus is interrupted by regions with sharpy distinct connectivity, structure, and function,
alternating with effector-specific (foot, hand, mouth) areas. These inter-effector regions exhibit
decreased cortical thickness and strong functional connectivity to each other, and to prefrontal,
insular, and subcortical regions of the Cingulo-opercular network (CON), critical for executive
action5 and physiological control6, arousal7, and processing of errors8 and pain9. This inter-
digitation of action control-linked and motor effector regions was independently verified in the
three largest fMRI datasets. Macaque and pediatric (newborn, infant, child) precision fMRI
revealed potential cross-species analogues and developmental precursors of the inter-effector
system. An extensive battery of motor and action fMRI tasks documented concentric
somatotopies for each effector, separated by the CON-linked inter-effector regions. The inter-
effector regions lacked movement specificity and co-activated during action planning
(coordination of hands and feet), and axial body movement (e.g., abdomen, eyebrows). These
results, together with prior work demonstrating stimulation-evoked complex actions4 and
connectivity to internal organs (e.g., adrenal medulla)10, suggest that M1 is punctuated by an
integrative system for implementing whole-body action plans. Thus, two parallel systems
intertwine in motor cortex to form an integrate-isolate pattern: effector-specific regions (foot,
hand, mouth) for isolating fine motor control, and a mind-body interface (MBI) for the integrative
whole-organism coordination of goals, physiology, and body movement.
.CC-BY-NC-ND 4.0 International licenseavailable under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
The copyright holder for this preprintthis version posted October 28, 2022.;https://doi.org/10.1101/2022.10.26.513940doi:bioRxiv preprint
MAIN
Beginning in the 1930s, Penfield and colleagues mapped human M1 with direct cortical
stimulation, eliciting movements from about half of sites, mostly of the foot, hand, or mouth1.
Although representations for specific body parts overlapped substantially11, these maps gave
rise to the textbook view of M1 organization as a continuous homunculus, from head to toe.
In non-human primates, organizational features inconsistent with the motor homunculus
have been described. Structural connectivity studies divided M1 into anterior, gross-motor, “old”
M1 (few direct projections to spinal motoneurons), and posterior, fine-motor, “new” M1 (many
direct motoneuronal projections)12,13. Non-human primate stimulation studies showed the body
to be represented in anterior M114, and the motor effectors (tail, foot, hand, mouth) in posterior
M1. Such studies also suggested that the limbs are represented in concentric functional zones
progressing from the digits at the center, to the shoulders on the periphery 3,15–17. Moreover,
stimulations could elicit increasingly complex and multi-effector actions when moving from
posterior to anterior M14,18,19.
During natural behavior, voluntary movements are part of goal-directed actions, initiated and
controlled by executive regions in the CON5,20. Neural activity preceding voluntary movements
can first be detected in the dorsal anterior cingulate cortex (dACC) or rostral cingulate zone21,
then in the pre-supplementary motor area (pre-SMA) and SMA22, followed by M1. These regions
all project to the spinal cord23, with M1 as the main transmitter of motor commands down the
corticospinal tract24. Efferent motor copies are received by primary somatosensory cortex (S1)25,
cerebellum, and striatum26 for online correction and learning. Tracer injections in non-human
primates demonstrated direct projections from anterior M1/CON to internal organs (e.g. adrenal
medulla) for preparatory sympathetic arousal in anticipation of action10. Post-movement error
and pain signals are relayed primarily to insular and cingulate regions of the CON, which update
future action plans8,9.
Resting state functional connectivity (RSFC) fMRI noninvasively maps the brain’s functional
networks27,28. Precision functional mapping (PFM) studies rely on large amounts of multi-modal
data (e.g., RSFC, tasks) to map individual-specific brain organization in greatest possible
detail29–31. Early PFM studies identified separate foot, hand, and mouth M1 regions23 with their
respective cerebellar and striatal targets26,27. These foot/hand/mouth motor circuits were
characterized by strong within-circuit connectivity and effector specificity in task fMRI23.
However, these circuits were relatively isolated and did not include functional connections with
control networks such as CON that could support the integration of movement with global
behavioral goals. A recent study showed that prolonged dominant arm immobilization
strengthened functional connectivity between disused M1 and the CON28,29, suggesting that the
CON’s role may extend beyond abstract action control and into movement coordination.
Here, we used the latest iteration of PFM with higher resolution (2.4 mm) and greater
amounts of fMRI (RSFC: 172 – 1,813 min/participant; task: 353 min/participant), and diffusion
data, to map M1 and its connections with highest detail. Results were verified in group-averaged
data from the three largest fMRI studies (Human Connectome Project [HCP], Adolescent Brain
Cognitive Development [ABCD] Study, UK Biobank [UKB]; total n ~ 50,000). Furthermore, we
placed our findings in cross-species (macaque vs human), developmental (neonate, infant,
child, and adult), and clinical (perinatal stroke) contexts using PFM data.
.CC-BY-NC-ND 4.0 International licenseavailable under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
The copyright holder for this preprintthis version posted October 28, 2022.;https://doi.org/10.1101/2022.10.26.513940doi:bioRxiv preprint
Beginning in the 1930s, Penfield and colleagues mapped human M1 with direct cortical
stimulation, eliciting movements from about half of sites, mostly of the foot, hand, or mouth1.
Although representations for specific body parts overlapped substantially11, these maps gave
rise to the textbook view of M1 organization as a continuous homunculus, from head to toe.
In non-human primates, organizational features inconsistent with the motor homunculus
have been described. Structural connectivity studies divided M1 into anterior, gross-motor, “old”
M1 (few direct projections to spinal motoneurons), and posterior, fine-motor, “new” M1 (many
direct motoneuronal projections)12,13. Non-human primate stimulation studies showed the body
to be represented in anterior M114, and the motor effectors (tail, foot, hand, mouth) in posterior
M1. Such studies also suggested that the limbs are represented in concentric functional zones
progressing from the digits at the center, to the shoulders on the periphery 3,15–17. Moreover,
stimulations could elicit increasingly complex and multi-effector actions when moving from
posterior to anterior M14,18,19.
During natural behavior, voluntary movements are part of goal-directed actions, initiated and
controlled by executive regions in the CON5,20. Neural activity preceding voluntary movements
can first be detected in the dorsal anterior cingulate cortex (dACC) or rostral cingulate zone21,
then in the pre-supplementary motor area (pre-SMA) and SMA22, followed by M1. These regions
all project to the spinal cord23, with M1 as the main transmitter of motor commands down the
corticospinal tract24. Efferent motor copies are received by primary somatosensory cortex (S1)25,
cerebellum, and striatum26 for online correction and learning. Tracer injections in non-human
primates demonstrated direct projections from anterior M1/CON to internal organs (e.g. adrenal
medulla) for preparatory sympathetic arousal in anticipation of action10. Post-movement error
and pain signals are relayed primarily to insular and cingulate regions of the CON, which update
future action plans8,9.
Resting state functional connectivity (RSFC) fMRI noninvasively maps the brain’s functional
networks27,28. Precision functional mapping (PFM) studies rely on large amounts of multi-modal
data (e.g., RSFC, tasks) to map individual-specific brain organization in greatest possible
detail29–31. Early PFM studies identified separate foot, hand, and mouth M1 regions23 with their
respective cerebellar and striatal targets26,27. These foot/hand/mouth motor circuits were
characterized by strong within-circuit connectivity and effector specificity in task fMRI23.
However, these circuits were relatively isolated and did not include functional connections with
control networks such as CON that could support the integration of movement with global
behavioral goals. A recent study showed that prolonged dominant arm immobilization
strengthened functional connectivity between disused M1 and the CON28,29, suggesting that the
CON’s role may extend beyond abstract action control and into movement coordination.
Here, we used the latest iteration of PFM with higher resolution (2.4 mm) and greater
amounts of fMRI (RSFC: 172 – 1,813 min/participant; task: 353 min/participant), and diffusion
data, to map M1 and its connections with highest detail. Results were verified in group-averaged
data from the three largest fMRI studies (Human Connectome Project [HCP], Adolescent Brain
Cognitive Development [ABCD] Study, UK Biobank [UKB]; total n ~ 50,000). Furthermore, we
placed our findings in cross-species (macaque vs human), developmental (neonate, infant,
child, and adult), and clinical (perinatal stroke) contexts using PFM data.
.CC-BY-NC-ND 4.0 International licenseavailable under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
The copyright holder for this preprintthis version posted October 28, 2022.;https://doi.org/10.1101/2022.10.26.513940doi:bioRxiv preprint
Two distinct functional systems alternate in motor cortex
Fig. 1| Precision functional mapping of primary motor cortex. a, Resting state functional connectivity
(RSFC) seeded from a continuous line of cortical locations in the left precentral gyrus in a single exemplar
participant (P1; 356 min resting-state fMRI). The six exemplar seeds shown represent all distinct
connectivity patterns observed (see Supplementary Movie 1 for complete mapping). Functional
connectivity seeded from these locations illustrated classical primary motor cortex connectivity of regions
representing the foot (1), hand (3), and mouth (5), as well as an interdigitated set of strongly
interconnected regions (2, 4, 6). See Fig. S1a and Supplementary Movie 2 for all highly-sampled
participants, Fig. S1b for within-participant replications, and Fig. S1c for group-averaged data. b, Discrete
functional networks were demarcated using a whole-brain, data-driven, hierarchical approach (see
Methods) applied to the resting-state fMRI data, which defined the spatial extent of the networks
observed in Fig. 1 (black outlines). Regions defined by RSFC were functionally labeled using a classic
block-design fMRI motor task involving separate movement of the foot, hand, and tongue (following34;
see32 for details). The map illustrates the top 1% of vertices activated by movement of the foot (green),
hand (cyan), and mouth (orange) in the exemplar participant (P1; see Fig. S1d for other participants). c,
The inter-effector connectivity pattern became more distinct from surrounding effector-specific motor
regions as connectivity thresholding increased from the 80th to the 97th percentile. RSFC thresholds
required to detect the inter-effector pattern were lower in individual-specific data (top) than in group-
averaged data (ABCD Study, bottom).
+- RSFC: Z(r)
80th percentile 90th percentile 97th percentile
IndividualGroup
Threshold:
Thresholding effect on functional connectivity maps
0.60.35
RSFC: Z(r)
1
2
3
4
5
6
1 2
3
6
4
5
Precentral gyrus
seeds
RSFC Network borders
Hand MouthFoot
Task activations
Precentral gyrus functional connectivitya
b c
.CC-BY-NC-ND 4.0 International licenseavailable under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
The copyright holder for this preprintthis version posted October 28, 2022.;https://doi.org/10.1101/2022.10.26.513940doi:bioRxiv preprint
Fig. 1| Precision functional mapping of primary motor cortex. a, Resting state functional connectivity
(RSFC) seeded from a continuous line of cortical locations in the left precentral gyrus in a single exemplar
participant (P1; 356 min resting-state fMRI). The six exemplar seeds shown represent all distinct
connectivity patterns observed (see Supplementary Movie 1 for complete mapping). Functional
connectivity seeded from these locations illustrated classical primary motor cortex connectivity of regions
representing the foot (1), hand (3), and mouth (5), as well as an interdigitated set of strongly
interconnected regions (2, 4, 6). See Fig. S1a and Supplementary Movie 2 for all highly-sampled
participants, Fig. S1b for within-participant replications, and Fig. S1c for group-averaged data. b, Discrete
functional networks were demarcated using a whole-brain, data-driven, hierarchical approach (see
Methods) applied to the resting-state fMRI data, which defined the spatial extent of the networks
observed in Fig. 1 (black outlines). Regions defined by RSFC were functionally labeled using a classic
block-design fMRI motor task involving separate movement of the foot, hand, and tongue (following34;
see32 for details). The map illustrates the top 1% of vertices activated by movement of the foot (green),
hand (cyan), and mouth (orange) in the exemplar participant (P1; see Fig. S1d for other participants). c,
The inter-effector connectivity pattern became more distinct from surrounding effector-specific motor
regions as connectivity thresholding increased from the 80th to the 97th percentile. RSFC thresholds
required to detect the inter-effector pattern were lower in individual-specific data (top) than in group-
averaged data (ABCD Study, bottom).
+- RSFC: Z(r)
80th percentile 90th percentile 97th percentile
IndividualGroup
Threshold:
Thresholding effect on functional connectivity maps
0.60.35
RSFC: Z(r)
1
2
3
4
5
6
1 2
3
6
4
5
Precentral gyrus
seeds
RSFC Network borders
Hand MouthFoot
Task activations
Precentral gyrus functional connectivitya
b c
.CC-BY-NC-ND 4.0 International licenseavailable under a
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
The copyright holder for this preprintthis version posted October 28, 2022.;https://doi.org/10.1101/2022.10.26.513940doi:bioRxiv preprint
100%
