Journal of Motor Behavior

ISSN: 0022-2895 (Print) 1940-1027 (Online) Journal homepage: https://www.tandfonline.com/loi/vjmb20

The Role of Primary Motor Cortex: More Than

Movement Execution

Sagarika Bhattacharjee, Rajan Kashyap, Turki Abualait, Shen-Hsing Annabel

Chen, Woo-Kyoung Yoo & Shahid Bashir

To cite this article: Sagarika Bhattacharjee, Rajan Kashyap, Turki Abualait, Shen-Hsing Annabel
Chen, Woo-Kyoung Yoo & Shahid Bashir (2020): The Role of Primary Motor Cortex: More Than
Movement Execution, Journal of Motor Behavior, DOI: 10.1080/00222895.2020.1738992

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Published online: 20 Mar 2020.

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 Journal of Motor Behavior, 2020
Copyright # Taylor & Francis Group, LLC

REVIEW ARTICLE
The Role of Primary Motor Cortex: More Than
Movement Execution
Sagarika Bhattacharjee1, Rajan Kashyap2, Turki Abualait3, Shen-Hsing Annabel Chen4,5,
Woo-Kyoung Yoo6, Shahid Bashir7,8
1
Department of Psychology, Nanyang Technological University, Singapore. 2Center for Research and Development in
Learning (CRADLE), Nanyang Technological University, Singapore. 3Physical Therapy Department, College of Applied
Medical Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. 4Lee Kong Chian School of
Medicine (LKC Medicine), Nanyang Technological University, Singapore. 5Office of Educational Research, National
Institute of Education, Nanyang Technological University, Singapore. 6Department of Physical Medicine and
Rehabilitation, Hallym University Sacred Heart Hospital, Anyang, South Korea. 7Neuroscience Center, King Fahad
Specialist Hospital Dammam, Dammam, Saudi Arabia. 8Berenson-Allen Center for Noninvasive Brain Stimulation, Beth
Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

ABSTRACT. The predominant role of the primary motor cor- neuron contributes to the corticospinal pathway, whereas
tex (M1) in motor execution is well acknowledged. However, the lower motor neurons innervate the skeletal muscle
additional roles of M1 are getting evident in humans owing to fibers situated at the periphery (Porter & Lemon, 1993).
advances in noninvasive brain stimulation (NIBS) techniques.
This review collates such studies in humans and proposes that With this structural construct, M1 is predominantly con-
M1 also plays a key role in higher cognitive processes. The sidered to only have a role in motor execution.
review commences with the studies that have investigated the In contrast, the PMA and other regions of the frontal
nature of connectivity of M1 with other cortical regions in light lobe such as the supplementary motor area (SMA) and
of studies based on NIBS. The review then moves on to dis- the cingulate motor area (CMA) (Chouinard & Paus,
cuss the studies that have demonstrated the role of M1 in
higher cognitive processes such as attention, motor learning, 2006) form the secondary motor areas. Many previous
motor consolidation, movement inhibition, somatomotor reviews have shown that these secondary motor areas are
response, and movement imagery. Overall, the purpose of the involved in cognitive processes such as planning, coord-
review is to highlight the additional role of M1 in motor cogni- ination, and selecting voluntary movement (Nachev
tion besides motor control, which remains unexplored. et al., 2008; Rizzolatti et al., 2002). For example,
Abbreviations: PMA: premotor area; SMA: supplementary
motor area; CMA: cingulate motor area; NIBS: Noninvasive Rizzolatti et al. (2002) consolidated the results of the
brain stimulation; TMS: transcranial magnetic stimulation; studies performed on primates and humans to conclude
tDCS: transcranial direct current stimulation; fMRI: functional that the ventral sectors of the PMA (including Brodmann
magnetic resonance imaging; rTMS: repetitive TMS; S1: pri- area 44) are involved in action organization, motor
mary sensory cortex; MEPs: motor evoked potentials; EMG: imagery, and action understanding. Similarly, Goldberg
electromyographic; ppTMS: paired-pulse TMS; EEG: electro-
encephalogram; CSP: cortical silence period; TBS: theta-burst (1985) and Roland et al. (1980) reported the involvement
stimulation; NMA: negative-motor area; SICI: short-interval of SMA in the organization of voluntary motor move-
intra-cortical inhibition ment. Borich et al. (2015) reviewed the role of primary
Keywords: cognitive functions, motor learning, primary
SMA in motor control, motor learning, and functional
motor cortex recovery. Though these studies open up vast opportuni-
ties for the exploration of M1, the possibility that M1
can play a crucial role in motor cognition remains
understudied.
Noninvasive brain stimulation (NIBS) techniques such
Introduction as transcranial magnetic stimulation (TMS) and transcra-
arly investigation of the motor cortex in humans nial direct current stimulation (tDCS) have provided evi-
E (Penfield & Boldrey, 1937; Woolsey, 1952) had
functionally divided the motor cortex into two major
dence that M1 might be involved in higher cognition.
NIBS can directly modulate M1 (in isolation) and estab-
areas: the primary motor cortex (M1) and premotor area lish a causal relationship between the activity of the
(PMA; Fulton, 1935). M1 is located in the precentral regions and the behavior. In this regard, it will be inter-
gyrus of the frontal lobe that plays a crucial role in the esting to lay out the NIBS-based studies that have indi-
cated (directly or indirectly) the role of M1 in higher
execution of voluntary movements (Pearson, 2000).
cognition. The present review will begin with a short
Histological examination of M1 has revealed the pres-
description of the anatomical, functional, and
ence of giant pyramidal neurons called Betz cells. Betz
cells are also known as upper motor neurons because
Correspondence address: Shahid Bashir PhD, Neuroscience
they send axons to the lower motor neurons situated in Center, King Fahad Specialist Hospital Dammam, Dammam,
the gray column of the spinal cord. The upper motor Saudi Arabia. e-mail: [email protected]

1
S. Bhattacharjee et al.

neurochemical connections of M1 with other cortical and subcortical networks have been demonstrated to be
subcortical regions. This will be followed by the descrip- involved in motor sequence performance (Bapi et al.,
tion of the studies that have provided evidence for the 2006). Thus, Bestmann et al. (2004) finding of the inter-
involvement of M1 during attention, learning, consolida- regional connections of M1 with these regions suggests a
tion, movement inhibition, observation, imagery, and possible contribution of M1 in performing a sequence of
sensory processes. Here, we would like to remind our motor actions. This is possible, as evidenced by another
readers that though the present review will mostly focus study showing the involvement of M1 and the primary
on the studies on humans, owing to the limited research sensory cortex (S1) in complex voluntary finger move-
on M1 in humans, relevant findings from animal studies ment (Shibasaki et al., 1993). In an interesting work,
will also be occasionally presented. Fox et al. (1997) recorded PET scans following the
stimulation of M1 by TMS. They found excitatory con-
nectivity of M1 with ipsilateral S1 and S2, ipsilateral
Overview of the Connectivity of M1 with Other
ventral and lateral PMA, and contralateral SMA. They
Cortical Regions
also reported inhibitory connectivity of M1 with contra-
M1 sends projections to the lower motor neurons in the lateral M1. Overall, the activation in other cortical
spinal cord and is interconnected with multiple brain regions following the stimulation of M1 suggested M1 to
regions through afferent and efferent pathways. Such be a “well-coordinated relay” involved in sending as
interregional structural connections of M1 have been well as receiving information.
extensively demonstrated in primates (Barbas & Pandya, Motor evoked potentials (MEPs) can also investigate
1987; Dum & Strick, 2002; Geyer et al., 2000; Holsapple such intercortical connections of M1 because they can be
et al., 1991; Luppino et al., 1993; Matelli et al., 1989; used to characterize the interaction of M1 with other
Orioli & Strick, 1989; Penfield & Boldrey, 1937; Petrides brain regions. MEPs are induced following single-pulse
& Pandya, 1984; Strick, 1985; Strick & Preston, 1983) as TMS over M1 (or any other brain region) and are meas-
well as in other mammals (Kaas, 1991; Sanes & ured from the surface of the muscles controlled by M1,
Donoghue, 2000). Several studies on humans have also such as the abductor pollicis brevis/longus muscle of the
suggested interregional connections of M1 with other cor- thumb, using electromyographic (EMG) recording
tical and subcortical regions using positron emission tom- (Thickbroom et al., 1999). MEPs generated by paired-
ography (PET; Fink et al., 1997; Grafton et al., 1993; pulse TMS (ppTMS) are also used to study various cor-
Honda et al., 1998) and functional magnetic resonance tico-cortical connections. ppTMS is a kind of TMS
imaging (fMRI; Rao et al., 1997; Xiong et al., 1999). where a subthreshold stimulus (conditioning stimulus) is
These neuroimaging techniques have good spatial reso- followed by a suprathreshold stimulus (test stimulus)
lution but mainly measure the level of oxygen in the separated by an inter-stimulus interval. The suprathres-
blood (Davis et al., 1998) and do not directly measure the hold stimulus determines the corticospinal output that
neural activity. Though the neural activity in the cortex leads to an MEP, while a subthreshold stimulus only
and the level of oxygen in the blood are related, such an excites the local cortical interconnections (Di Lazzaro
indirect way of measurement restricts our understanding et al., 2002). Thus, by combining a subthreshold pulse
of the complete functionality of an area in the brain. with a suprathreshold pulse, one can assess the effects of
Moreover, because the connectivity defined between two other cortical connections on the cortical output of M1
cortical regions is based on the correlation measures (Ziemann et al., 1998). An advantage of using ppTMS
between the imaging signals and the behavior (Hipp & for investigating the cortico-cortical connection is that it
Siegel, 2015), the precise nature and the causality-based can reveal whether the nature of the connection is excita-
dynamics behind functional connectivity remain elusive. tory or inhibitory (based on an increase or decrease
In this aspect, TMS has been widely utilized to modu- in MEP).
late cortical regions of cortex. Two types of TMS—the Using ppTMS over the dorsal PMA with a condition-
sub- and supra-threshold repetitive TMS (rTMS)—have ing pulse of 90% of the active motor threshold, Civardi
been used to stimulate M1. The resultant changes in the et al. (2001) showed that the excitability of M1 (demon-
cortical and subcortical motor areas could be observed strated by MEP amplitude) was significantly reduced.
using fMRI. In one such study by Bestmann et al. Alternatively, they also found that the excitability of M1
(2004), signal change in the cortical and subcortical could be increased when the conditioning pulse was
motor regions was measured when the subjects received applied at 120% of the active motor threshold following
high-frequency rTMS over the left sensorimotor cortex PMA stimulation. Support for such findings come from
(M1/S1). They concluded that the activity in M1 propa- the studies that have found both the inhibitory (Cash
gates to other cortical and subcortical regions such as et al., 2017; Ferbert et al., 1992; Fiori et al., 2017) and
PMA, posterior SMA, CMA, cerebellum, thalamus, and excitatory (Hanajima et al., 2001; Mass
e-Alarie et al.,
putamen (Bestmann et al., 2004). Such cortical and 2016) interactions of M1 with ipsilateral and

2 Journal of Motor Behavior

 The Role of Primary Motor Cortex: More than Movement Execution

contralateral cortical regions such as the dorsal PMA, 2009; Roy & Gorassini, 2008). These studies indicate
posterior parietal cortices, SMA, and cerebellum (Reis that M1 receives multiple inputs from regions of both
et al., 2008). Mochizuki et al. (2004) specifically found central and peripheral nervous systems, which could be
an inhibitory connection between the dorsal PMA and both excitatory and inhibitory. In sum, the traditional
contralateral M1. They applied conditioning and test view that M1 is only an endpoint of motor processing in
stimulus over the right dorsal PMA and the left M1, the brain can be inferred to not be entirely accurate
respectively, with an inter-stimulus interval of 4, 6, 8, because it is also involved in the integration of signals
10, 12, 16, and 20 ms. They found the MEP generated along with other motor regions.
following test stimulus at M1 to be significantly reduced, The methodologies mentioned above provided an idea
and the effect was maximum at the inter-stimulus inter- about the type of spatial connectivity (excitatory/inhibi-
val of 8–10 ms. Recently, Lafleur et al. (2016) have tory) of M1 with other brain regions. The measurement
reviewed the studies using ppTMS to demonstrate the of the electrophysiological response using electroenceph-
connectivity of M1 with the contralateral M1, PMA, and alogram (EEG) following TMS is also helpful in under-
cerebellum. They have also specified that the nature of standing the spatio-temporal dynamics of the brain. In
this connectivity (excitatory/inhibitory) could vary this technique, one particular cortical region is stimulated
depending on the intensity and inter-stimulus interval of by TMS and the change in the electrophysiological sig-
the ppTMS paradigm. Overall, these studies demon- nals across other cortical regions is recorded. Ilmoniemi
strated that M1 is not only connected to other cortical et al. (1997) demonstrated that EEG responses were
regions by excitatory influences but also connected with potentiated in the homologous contralateral area in about
the inhibitory interneurons from other cortical regions. 22 ms following TMS over M1. Similarly, Esser et al.
The presence of both excitatory and inhibitory intercon- (2006) measured the cortical responses (with EEGs) to
nections with other cortical regions provides a structural single-pulse TMS over M1 before and after applying
basis for the possible role of M1 in higher-order cogni- rTMS to the PMA. They demonstrated that EEG
tive functions. responses at latencies of 15–55 ms were significantly
Similar to ppTMS described above, the interregional enhanced at the electrodes located at the PMA of both
connections can also be demonstrated by applying rTMS hemispheres. Similarly, Litvak et al. (2007) localized
over a non-primary motor area followed by a single- sources at the midline frontal area peaking after 28 ms of
pulse TMS over M1. The overall effect on M1 can be TMS over M1. They localized the sources in a temporal
“excitatory” or “inhibitory” depending on the various sequence and found sources peaking at an ipsilateral
stimulation paradigms used for rTMS (e.g., frequency; temporoparietal junction (with a delay of 35 ms) and
Fitzgerald et al., 2006). The MEP amplitudes are reduced the ipsilateral (with a delay of 30 ms) and middle cere-
when low-frequency rTMS is applied over the dorsal bellum (with a delay of 50 ms). The sequential activa-
PMA (Gerschlager et al., 2001), whereas they are tion of various cortical regions discussed above
enhanced when high-frequency rTMS is applied over the suggested the propagation of activity following stimula-
PMA (Fitzgerald et al., 2006). Such changes in MEP tion over M1 not only to the lower motor neurons but
indicate that the PMA might have both inhibitory and also to the other cortical and subcortical regions. With
excitatory connections with M1. This is further supported that said, we want to emphasize that these studies also
by Kobayashi et al. (2004) in a study where they asked indicate that M1 must be involved in the integration of
the participants to perform a sequential key-pressing task multiregional influences. In this process, it also executes
with the index finger. These authors applied rTMS (1 Hz the commands received from higher-order motor regions.
for 10 min with an intensity below the motor threshold) Similarly, tDCS has also been used to investigate the
over the ipsilateral M1, contralateral M1, ipsilateral connectivity of M1 with other brain regions. tDCS stud-
PMA, or vertex. The motor performance was monitored ies are limited because the appropriate montage that
for each participant before and after rTMS. They found could stimulate the target region (like the motor cortex)
that the rTMS of M1 resulted in shorter execution times is difficult to ascertain, and there are inconsistencies
of the motor task performed by the ipsilateral hand, regarding this in the literature (Ferreira et al., 2019).
whereas the performance with the contralateral hand was Although computational analysis paradigms that could
unaffected. They concluded that rTMS over M1 can help in the montage decision process for other cognitive
improve the motor function of the ipsilateral hand by functions are available (Bai et al., 2014; Bhattacharjee
releasing the contralateral M1 via transcallosal inhibition et al., 2019), the mechanism of action of tDCS still
(Kobayashi et al., 2004). These functional connections of remains an area requiring investigation (Caumo et al.,
M1 are not limited only to the central nervous system. 2012; Pelletier & Cicchetti, 2015). Nevertheless, Polan
ıa
Stimulating the peripheral nerves (measured by H-reflex) et al. (2012) investigated the resting-state fMRI before
before M1 is stimulated by a TMS impulse can cause and after tDCS over M1. They found that the anodal
excitatory changes in the resultant MEP (Devanne et al., stimulation of M1 significantly increases the functional

3
S. Bhattacharjee et al.

coupling between the left thalamus and ipsilateral M1. In possibility of M1 to participate in higher cognitive proc-
contrast, the cathodal stimulation of M1 decreases the esses such as skill learning.
functional coupling between the left M1 and contralateral
putamen. This shows that M1 is involved in the cortico- M1 and Attention
striatal and thalamocortical pathways, which are crucial
circuitries for motor cognition. M1 is found to be differentially activated when atten-
tion is directed toward an action compared with when it
is not. This is commonly observed in fMRI studies when
M1 and Neurochemical Pathways participants are asked to simultaneously perform a motor
The mesocorticolimbic projection that involves dopa- movement and a distractor task such as counting back-
mine as a signaling pathway plays an essential role in ward (Johansen-Berg & Matthews, 2002). A significant
higher cognitive functions (Alcaro et al., 2007). reduction in the fMRI signal for the dual task (both
Nieoullon and Coquerel (2003) reviewed the role of motor movement and distractor task) compared with that
dopamine in action, emotion, motivation, and cognition. for the single task (only motor movement) in the pre-
In the context of M1, although its role in regulating central gyrus (M1) (especially in the motor subarea 4p
movement via basal ganglia is known, its involvement in posterior) was reported (Johansen-Berg & Matthews,
the dopaminergic signaling pathway is still not known. 2002). Similarly, in a study by Binkofski et al. (2002),
The cerebral cortex sends glutamatergic projections to participants performed a visual task while constantly
the striatum that also receives dopaminergic projections moving their index finger. They found different subareas
from the substantia nigra and ventral tegmental area of M1 to be active when motor action was accompanied
(Sesack & Pickel, 1992). These corticostriatal neurons by a visual attention task. In particular, they discovered
project back to the cerebral cortex by a series of recur- that the subarea 4p within M1 is activated when attention
rent parallel loops, via the thalamus (Bamford et al., is paid. The authors further reported that the subarea 4a
2004). Evidence shows that M1 also sends dopaminergic (anterior) within M1 is activated when attention is not
projections to the striatum. Strafella et al. (2005) applied required for action. Because attention toward action is an
rTMS over M1 and measured the changes in the extra- important but subtle aspect of M1 activation, we high-
light a few TMS studies that have investigated the role
cellular dopamine concentration using [11C] raclopride
of M1 in motor action accompanied by attention. For
and PET in healthy human subjects. They found that
example, Conte et al. (2007) applied the 5-Hz rTMS
rTMS over the left M1 resulted in the reduced binding
conditioning stimulus to the PMA and delivered test
of [11C] raclopride in the left putamen. Thus, they dem-
stimuli over the hand motor area at the suprathreshold
onstrated that rTMS over the left M1 activated the corti-
intensity in trains of 10 stimuli. They recorded MEP size
costriatal fibers that project to the putamen and lead to
and cortical silence period (CSP) duration during three
focal dopamine release at the projected site. The same
attention-demanding conditions: “relaxed,” “target hand,”
inference was potentiated when Lang et al. (2008) demon-
and “non-target hand.” rTMS trains elicited a larger
strated that administration of the dopamine receptor agon-
MEP size facilitation when the subjects looked at the tar-
ist, pergolide, resulted in the suppression of cortical
get hand, whereas the CSP remained unchanged during
excitability following a low-frequency rTMS over M1 all the three conditions. Furthermore, they found that the
compared with a placebo. Similarly, in rats, the stimula- MEP facilitation during the “target hand” condition could
tion thresholds necessary to evoke a motor response (after be decreased if conditioning stimulation to the premotor
stimulation of the caudal M1) were increased when D2- cortex is provided. Overall, attention toward action influ-
receptors located in the M1 forelimb were blocked by the ences the excitability of M1 through the connections
intracortical injection of raclopride (Hosp et al., 2009). from the premotor cortex to M1.
We highlight the role of dopamine terminals and receptors
in M1 because they play an important part in skill teach-
ing (Molina-Luna et al., 2009). A review by Hosp and M1 and Learning
Luft (2013) suggested that these dopaminergic fibers Learning is an important higher-order cognition task
innervating M1 might also be involved in motor learning that has wide implications for daily activities. In this sec-
and motor cortex plasticity. The study further indicated tion, we will discuss the crucial role of M1 in learning,
that the investigation of the dopaminergic networks in M1 particularly in the acquisition of motor skills. The
might be useful for the rehabilitation of learning and cog- involvement of M1 in learning can be researched by
nitive deficits seen in Parkinson’s disease or other trau- evaluating its activation in people who either learn new
matic brain injuries. Altogether, the above findings movements or practice certain motor skills for a long
indicate an involvement of M1 in modulating the dopa- time, such as musicians. The overall volume of the
minergic corticostriatal pathway. This suggests the motor areas in musicians is found to be more than that

4 Journal of Motor Behavior

 The Role of Primary Motor Cortex: More than Movement Execution

of the motor areas in their counterparts (Gaser & practice is needed to elicit a TMS-induced movement in
Schlaug, 2003; M€unte et al., 2002). Moreover, the age at the practiced direction. Such changes suggest that the
which a person begins their musical training is inversely observed increase in the M1 volume and plasticity as the
related to the size of M1 in both hemispheres (Amunts practice of the skill is prolonged is not associated with
et al., 1997). In addition to the long-term structural the increased motor execution. Instead, it is related to an
changes of M1, long-term functional changes occur increase in motor skills. Recently, Tanaka et al. (2011)
when fine motor skills are trained over an extended reviewed the studies that showed the modulation of
period. Transient changes in cortical networks within M1 motor memory formation and motor skill learning in
begin with minimal practice (Classen et al., 1998); how- both healthy humans and stroke patients following NIBS
ever, long-term modifications of M1 require more exten- over M1. This led them to conclude that M1 must have
sive practice (Karni et al., 1998; Sanes & Donoghue, a role in the retention of new motor memories as well as
2000). Karni et al. (1998) argued that the acquisition of in the consolidation of motor memory, which will be the
proficiency in motor performance occurs in two distinct topic of discussion in the next section.
functional learning stages. In the first stage, the repeti-
tion of a given sequence increases the activation in the
M1 and Motor Consolidation
motor cortex, thereby expanding the representation of the
repeated sequence. For example, Hund-Georgiadis and Electrophysiological experiments (Kashyap et al.,
Von Cramon (1999) found musicians to recruit larger 2016a, 2016b; Praeg et al., 2006) and neuroimaging-
ipsilateral and contralateral M1 areas at the early stages based meta-analysis studies (Hardwick et al., 2013;
of training, known as the “fast learning phase.” In the Lohse et al., 2014) demonstrate the involvement of
second stage, after about three weeks of training, the motor areas in various stages of learning. Motor areas
trained sequence results in extensive representation in such as the SMA, M1, PMA, parietal cortex, dorsolateral
M1, known as the consolidation of learned sequence. prefrontal, basal ganglia, parahippocampal cortex, and
This extensive representation in M1 further grows with cerebellum are found to be involved in motor learning
repeated practice and is highly correlated with specific (Hardwick et al., 2013; Lohse et al., 2014). Though other
gains in performance, also known as the “slow learning regions have received considerable interest for their role
phase.” Though studies on humans are limited, the in motor consolidation, little has been discussed about
in vivo studies on rat brain revealed that the late slow M1. In an electrophysiological study by Bender et al.
phase of skill learning is accompanied by motor map (2004), the activity in M1 was found to last as long as
reorganization and synapse formation (Kleim, 2004). 600 ms after movement execution. In an fMRI study by
Altogether, the studies suggest that M1 not only structur- Steele and Penhune (2010), the activity in M1 during the
ally grows but also functionally develops as the practice early learning process (task learned on day 1) was found
of the motor skill is prolonged. Penhune and Steele to be predictive of the degree of consolidation in the
(2012) reviewed the neuroimaging studies that demon- later phases on day 2. These studies suggest that M1’s
strate the role of M1, basal ganglia, and cerebellum in involvement in the post-execution stage cannot be
motor learning. Their review concluded that M1 is the denied, but its specific role during this stage should be
storage site of a newly learned movement and probably further investigated.
grows as a part of the distributed network for learning After a newly learned movement is executed, it gets
that includes the PMA and parietal cortex. consolidated over time as a part of the complete learning
The NIBS technique is extensively used in neuroimag- phase. Neuroimaging studies have shown that during the
ing studies to investigate the role of M1 during motor consolidation phase of a new motor skill, a shift in brain
learning (Gaser & Schlaug, 2003; M€unte et al., 2002). activity can be seen from the prefrontal regions to the
For example, a TMS study found that training aimed at PMA, posterior parietal cortex, and cerebellum.
learning a piano sequence results in an increase in the However, the specific phase in which the process of tran-
M1 excitability (Pascual-Leone et al., 1995). These find- sition from motor execution to motor consolidation
ings were further confirmed when a TMS study found occurs is still elusive. An attempt to clarify this was
that the cortical network representation in M1 changes made by Muellbacher et al. (2002) in their study,
following the prolonged practice of movements (Classen wherein they tested whether M1 plays a role during early
et al., 1998). In the study, focal TMS was applied over motor consolidation. They asked their subjects to per-
M1 to evoke isolated and directionally consistent thumb form fast finger movements that could rapidly improve
movement. The participants were asked to practice movement acceleration and muscle force generation.
thumb movement in different directions. Subthreshold They found that low-frequency rTMS specifically over
TMS was applied to evoke the movement in a recently M1 disrupted the retention of behavioral improvement.
practiced direction before returning to the original move- However, rTMS (over M1) did not affect the basal motor
ment. It was found that at least 15–30 min of continuous behavior, task performance, motor learning by

5
S. Bhattacharjee et al.

subsequent practice, or recall of the newly acquired with excitatory effect over M1. This establishes the cru-
motor skill. Disruption in the retention of behavioral cial role of M1 in implicit sequence learning. Similar to
improvement indicated that human M1 is specifically this study, other studies observed the effect of intermit-
engaged in the early stage of motor consolidation. tent TBS on M1 in subcortical stroke patients. It was
Besides the early stage of the motor consolidation pro- found that intermittent TBS improves the training effects
cess, some studies have demonstrated the necessity of in a precision grip task (for details, refer to the reviews
adequate M1 functioning for the offline improvement of by Censor & Cohen, 2011; Reis et al., 2008; Tanaka
newly acquired motor skills. For example, Overduin et al., 2011).
et al. (2009) found that the application of rTMS over M1 A few studies have found the motor consolidation pro-
before a motor learning task did not interfere with the cess in M1 to be dependent on the awake versus sleep
initial motor adaptation. However, the performance state of the brain. Robertson et al. (2005) found that the
declined when the task was retested on the next day. It disruption of M1 with rTMS interferes with the improve-
was also observed that in some situations, inhibition of ments over the day but not overnight. Participants were
M1 resulted in disruptive effects on motor preparation asked to learn a finger sequence, and movement and ser-
but not on motor execution (Perez & Cohen, 2009; Reis ial reaction time were measured. After skill acquisition
et al., 2009). Censor and Cohen (2011) found that rTMS either in the morning (8.00 a.m.) or evening (8:00 p.m.),
applied over M1 on day 1 negatively affected the per- rTMS was applied over M1 and the skill was retested
formance of subjects tested on day 2. Even applying sin- after 12 h. Results showed that the group that received
gle-pulse TMS over the contralateral M1 during a rTMS over the daytime showed significantly lesser
voluntary movement effected the motor training, thereby improvement on a subsequent day compared with sham.
reflecting the presence of long-lasting motor memories However, the increase in performance was not impaired
(Buetefisch et al., 2011). Altogether, these studies sug- by rTMS over M1 in the individuals who slept between
gest that M1 plays a role in the offline process of motor two sessions. This was an important finding as it showed
memory consolidation. Similarly, the causal role of M1 that the neural circuit that includes M1 contributes to the
in learning was further demonstrated by disrupting the motor learning process. In a similar experimental para-
M1 activity by 15 min of 1-Hz rTMS in between learn- digm, Cohen et al. (2005) showed that M1 is involved in
ing of two separate hand movement tasks. It was found movement-based learning over the day but has no role in
that inhibition of the M1 activity in the group receiving goal-based learning overnight. Similarly, Iezzi et al.
rTMS resulted in the better performance of task 2 com- (2010) reported the degradation of practice-related
pared with the group that did not receive rTMS improvement in movement amplitude, peak velocity, and
(Richardson et al., 2006). This enhancement indicates peak acceleration after applying TBS with inhibitory
that the existence of previous motor learning skills might effect over M1. Participants were asked to perform two
interfere with learning a new one. Moreover, such reten- types of tasks involving either motor practice (task 1) or
tion of skills and interference between skill learnings are motor consolidation (task 2). TBS was applied over M1
linked at the level of M1. to both the groups under either real or sham conditions
Theta-burst stimulation (TBS) is another TMS tech- while performing the tasks. In task 1 and task 2 groups,
nique that has helped to evaluate the role of M1 in mem- the motor retention was tested 30 and 15–30 min after
ory consolidation. TBS produces long-lasting excitatory the motor practice session ended, respectively. The motor
or inhibitory effects on motor physiology and behavior consolidation in task 2 group was tested 24 hour after the
(Huang et al., 2005). TBS studies are referred here practice session. The task performance during practice
because there is no direct evidence that indicates the and retention was found to be degraded following TBS
involvement of M1 in consolidating (along with other in both the groups, but the motor consolidation process
downstream motor areas) the memory of an already per- remained unchanged when tested on the following day.
formed task. To decipher this, Wilkinson et al. (2010) This shows that M1 is involved in practice-related
investigated the association of several cortical regions improvement during early motor retention but not in the
with implicit learning sequences. Five age- and IQ- overnight motor consolidation process of a voluntary fin-
matched groups of healthy participants were administered ger movement.
TBS with inhibitory effect over (1) M1, (2) SMA, (3) Learning can be modulated by the application of tDCS
dorsolateral prefrontal cortex. They also received (4) over certain regions. tDCS is a type of NIBS that can
intermittent TBS with excitatory effect over the areas modulate cortical excitability. Anodal stimulation excites
and sham TBS. Interestingly, it was found that compared the underlying cortical region, whereas cathodal stimula-
with sham TBS, sequence learning was abolished by tion is inhibitory. Nitsche et al. (2003) demonstrated an
TBS with an inhibitory effect over M1. However, enhancement in implicit motor learning with anodal
sequence learning was not significantly affected by TBS stimulation over M1 (Antal et al., 2004). Reis et al.
with inhibitory effect over the other areas or by TBS (2009) also demonstrated the role of M1 in the motor

6 Journal of Motor Behavior

 The Role of Primary Motor Cortex: More than Movement Execution

consolidation process by applying tDCS over M1 while produces the symptom of spasticity, signifying the loss of
a novel motor skill task was learned for five days. The motor inhibition (Barnes & Johnson, 2008; Laplane
anodal tDCS over M1 resulted in improved task perform- et al., 1977).
ance, which was measured both within and between The findings from the neurosurgical stimulation study
days. The study concluded that the existence of a motor by Penfield and Rasmussen (1950) described above
consolidation mechanism within M1 could be modulated opened up a new field of investigation. Recently,
by tDCS. Recent meta-analyses by Hashemirad et al. Filevich et al. (2012) reviewed such studies and con-
(2016) and Savic and Meier (2016) have demonstrated cluded that the inhibition of movement following the
that tDCS over M1 can modulate motor sequence learn- stimulation of NMAs might not reflect the only disrup-
ing and consolidation. In this regard, a natural step that tion of motor action. However, such observation might
follows after we construe motor learning and consolida- also indicate that NMAs contribute to inhibitory mecha-
tion is to figure out if M1 has a role in motor inhibition. nisms depending on the ecological condition. They
This discussion is significant because motor inhibition is reported that such NMAs could be seen in the motor
important for motor learning (Kolasinski et al., 2017). cortex, SMA, and inferior frontal gyrus in abundance.
This will be discussed in the next section. However, only a few studies have specifically investi-
gated the NMAs in M1. Shibasaki and Hallett (2006)
observed that the signals from cortical regions such as
M1 and the Inhibition of Movement
SMA, PMA, and M1 could recruit inhibitory interneur-
The corticospinal tract (CST) is the longest tract in the ons in the spinal cord. This suggests that M1 might as
CNS, originating in layer 5 pyramidal neurons in the well have a considerable role in inhibiting muscle activ-
sensorimotor cortex and terminating in the spinal cord ity. Likewise, Bonnard et al. (2009) found that a cogni-
and it plays a critical role in controlling voluntary move- tive process of prior intention can resist the involuntary
ment (Lemon, 2008, 2019; Welniarz et al., 2017). In the movement elicited by suprathreshold TMS applied over
spinal cord, the CST fibers project to the dorsal and inter- M1. They observed that the amplitude of the TMS-
mediate portions of the gray matter and innervate inter- evoked N100 component was higher at the central elec-
neurons, which in turn control motor neurons (2019, trodes (FCz, C1, Cz, CP1, and CP3) when participants
Welniarz et al., 2017; Lemon, 2008). tried to resist an involuntary motor movement (elicited
Ebbesen and Brecht (2017) have reviewed the studies by TMS) compared with the condition when they
performed on eutherian mammals and concluded that M1 voluntarily did it. These studies point toward the possible
might have an important contribution to motor inhibition role of M1 in the inhibition of voluntary action.
in addition to motor generation. The review starts with a Interhemispheric inhibitory control was also demon-
discussion of the motor map, which is important for strated in a TMS study by Schnitzler et al. (1996). These
motor execution. authors applied a conditioning TMS stimulus to the M1
The motor map was first demonstrated on a dog by of one side of the brain. They then recorded the CSP fol-
Fritsch (1870), which was later confirmed on monkeys by lowing a test stimulus in the M1 on the other side of the
Ferrier (1875). A decade later, neurosurgeons Penfield and brain with an inter-stimulus interval of 10–20 ms. They
Rasmussen (1950) confirmed the presence of motor hom- found a significant reduction in the CSP, which sug-
unculus in awake human subjects by stimulating the motor gested that the inhibitory neurons within M1 received
cortex during surgeries. These subjects often reported a inhibitory connections from the opposite M1 as well
sense of paralysis and numbness focal to specific body (Schnitzler et al., 1996). With that said and considering
parts after the stimulation of the motor homunculus. that intensive research on the topic is required, we call
Thus, it seems that motor homunculus is not a pure for future studies to investigate the role of M1 in inhibit-
“motor map” but a map of “movement suppression.” ing a voluntary action.
Subsequently, many studies have reported the presence of
so-called negative-motor areas (NMAs: motor areas that
M1 and Sensory Feedback
cause movement inhibition) in the motor cortex (Ikeda
et al., 1995; L€
uders et al., 1995; Mikuni et al., 2006; Nii Some studies have reported that M1 is influenced by
et al., 1996). Finally and most importantly, they report sensory feedback on the motor cortex triggered by sen-
that a lesion in the motor cortex of a rodent typically sory stimulation. For example, a TMS study (Ruge et al.,
interferes with motor movement but does not exterminate 2014) measured the MEP and short-interval intracortical
it. Instead, the interference is also associated with inhibition (SICI) following TMS over M1. The partici-
impaired movement suppression (Ebbesen & Brecht, pants received electrical stimulation at the dorsum of
2017). This can be typically seen in humans, where the hand while performing a visual discrimination task. The
immediate symptom of an acute cortical lesion is weak- authors found that attention to the skin overlying a muscle
ness and loss of movement; however, the chronic lesion changed the corticospinal excitability but had no effect on

7
S. Bhattacharjee et al.

the SICI of the muscle. However, attention to a distant hearing of finger tapping movements (Caetano et al.,
area on the skin affected MEP but reduced the SICI. In 2007). The results showed highly similar activation pat-
both cases, H-reflex was unaffected, suggesting that sen- terns before, during, and after the motor action under all
sory feedback from skin influences the excitability within three conditions. There is strong support from NIBS
circuits comprising M1. A review by Hatsopoulos and studies in this aspect. In particular, MEPs of hand
Suminski (2011) has listed the studies that point toward muscles after TMS in the motor cortex were found to be
the heterogeneities in M1 responses to visual and somato- increased in subjects who observed hand movements
sensory stimuli. We will, therefore, divide the topic of the (Fadiga et al., 1995). The MEP pattern was similar to
role of M1 into two subsections related to the motor the pattern of muscle activity recorded when the subjects
responses to visual and somatosensory stimuli and indi- executed the observed action. Roosink and Zijdewind
vidually discuss them in detail. (2010) compared the MEPs using TMS for rest, observa-
tion, imagery, and execution of simple and complex
Motor Observation movements. They found an increase in corticospinal
excitability during the observation of complex motor
The observation of another person’s movement leads
tasks. Similarly, using TMS, Naish et al. (2014) reported
to the activation of the motor cortex of the observer
the facilitation of corticospinal excitability during motor
(Ocampo & Kritikos, 2010). Such neuronal activity is
observation. In particular, they reported that early facili-
referred to as “mirror” activity. Mirror neurons are visuo-
tation of the corticospinal excitability following action
motor neurons that are activated when a monkey per-
observation occurs around 90 ms from action onset. This
forms an action. They are also activated when the
is followed by the modulation of the activity specific to
monkey observes another individual (monkey or human)
the muscles involved in the observed action at about
performing a similar action (Di Pellegrino et al., 1992;
200 ms after action onset. Altogether, these studies indi-
Gallese et al., 1996;; Rizzolatti et al., 1996). The pres-
cate the possibility of the existence of mirror neurons in
ence of mirror neurons was originally demonstrated in
humans that become activated during motor observation.
premotor and parietal cortices (Di Pellegrino et al., 1992;
The ability to understand the intention of a person by
Gallese et al., 1996). Their presence in M1 has also been
observing their actions has been explained from the
documented in macaques (Vigneswaran et al., 2013) and
framework of predictive coding by Kilner et al. (2007).
humans, as summarized in a review (refer, Kilner &
These authors found that neurons from the ventral PMA
Lemon, 2013). However, the exact role of mirror neu-
(F5 area) and M1 are part of the mirror neuron system
rons in M1 for human needs further investigation.
that analyzes the intent during motor observation. In add-
Focusing on M1, Nishitani and Hari (2002) reported
ition, another study found that the onset times for the
that M1 activates during the imitation of a movement.
M1 activity for both “execution of the action” and
Here, they investigated the cortical dynamics using mag-
“action observation” are similar (Babiloni et al., 2002).
netoencephalography when subjects were under three
In a similar vein but from a different perspective, sup-
conditions: (1) observing movement-related still pictures
pression of the M1 activity was seen approximately 2 s
such as a performing athlete or a person lifting a glass,
before the initiation of an action. This suppression
(2) imitating the action shown in the still pictures, and
occurred earlier for self-executed action compared with
(3) executing the action. Under all the conditions, the
the observation of the action (Caetano et al., 2007). This
activation bilaterally progressed from the occipital cortex
demonstrates that M1 is involved in action prediction
to the temporal region, the inferior parietal lobule, the
both in performance and observation of the action. The
frontal lobe (Broca’s area), and finally to M1. The sig-
role of M1 in the language comprehension of action-
nals of Broca’s area and M1 were significantly stronger
related verbs has been demonstrated by Repetto et al.
during the imitation of the movement than during obser-
(2013). They found specific inhibition in processing
vation and execution. These findings suggested that still
verbs that refer to action compared with abstract verbs
pictures that imply motion activate the human motor
after applying rTMS over the bilateral hand-related
neuron system in M1. This was supported by Caspers
region in M1. A possible explanation could be that the
et al. (2010), who found that bilateral networks compris-
mechanisms that predict a motor action are also involved
ing the frontal premotor, parietal, and temporo-occipital
in analyzing the intent when a word with motor action
cortices are activated during motor observation.
is displayed.
Likewise, the electrophysiological techniques such as
EEG and MEG have found alpha (10 Hz) and beta
Somatosensory Responses in MI
(20 Hz) band rhythms during movement execution as
well as during motor observation (Babiloni et al., 2002; Multiple studies have shown that M1 is activated fol-
Cochin et al., 1999; Hari et al., 1998). A recent study lowing somatosensory stimulation such as tactile stimula-
used MEG to compare the modulations of the M1 oscil- tion, perturbation, and passive movement (for details,
latory activity between the execution, observation, and refer to Nevalainen et al., 2014). However, most of these

8 Journal of Motor Behavior

 The Role of Primary Motor Cortex: More than Movement Execution

activations were thought to be the long-loop “reflex” imagery task (Rossini et al., 1999). Such enhanced
activations. The function of this reflex was to use sen- MEPs in the peripheral muscle could be attributable to
sory muscle information to activate the same or synergis- the corticospinal facilitation effect of mental imagina-
tic muscle. It has been argued that these long-loop tions of the motor task. Ganis et al. (2000) found that
reflexes can also perform higher-order cognitive func- the role of M1 in motor imagery is time-specific. In their
tions (Gielen et al., 1988). For example, when neurons in experiment, participants were asked to mentally rotate
these loops receive information from multiple muscle pictures of hands and feet while single-pulse TMS over
inputs, they can integrate this sensory feedback to gener- M1 was applied at two different time points (400 and
ate an appropriate response. Pruszynski et al. (2011) have 650 ms after the onset of the visual stimulus). The aim
demonstrated that shoulder muscle response occurs was to investigate whether interference with M1 process-
approximately 50 ms after pure elbow displacement, and ing would affect the response times of the mental
this phenomenon can be potentiated by applying TMS imagination of the rotation task. The response times
over M1. This shows the potential link between M1 proc- were slower when TMS was applied at the later time
essing and multi-joint integration in humans. Because the point (650 ms), but they were not affected at the earlier
research on this topic is limited, more research is needed time point (400 ms). This finding indicates that M1
to investigate the hypothesis that M1 permits feedback might be involved in the processing of mental imagin-
from the peripheral sensory information that can influence ation of the rotation task, but its involvement occurs at
the voluntary control over motor execution. relatively late time points. Similarly, interhemispheric
inhibition by the contralateral M1 in motor imagery was
found by Tomasino et al. (2005). They found that the
Motor Imagery
ability to mentally rotate both right and left hands was
In the previous section on motor learning, we dis- reduced when TMS over the left M1 was applied.
cussed that there are structural and functional changes Following up on involvement of M1 during mental
following the motor skill practice that is continued over imagery tasks, Ruffino et al. (2017) reviewed papers that
a long period. Interestingly, studies have suggested that applied single-pulse TMS over M1 and measured the
mental rehearsal without actually performing the motor MEPs. They concluded that motor excitability is
act can result in skill-enhancement effects (Carrasco & increased during motor imagery. Along the same lines,
Cantalapiedra, 2016; Pascual-Leone et al., 1995). It has Marconi et al. (2007) showed that this increase in motor
also been demonstrated that the combination of both excitability is specific to the muscle that is being
physical and mental training results in greater improve- included in the imagined movement. Some studies
ment in performance compared with any of the practice recorded the SICI following the application of ppTMS
methods alone (Allami et al., 2007; Avanzino et al., over M1. They found that SICI was significantly reduced
2009; Frank et al., 2014; Smith et al., 2007; 2008). In during the imagination of finger movement (Abbruzzese
this context, behavioral and neuroimaging studies have et al., 1999; Kumru et al., 2008; Liepert & Neveling,
found that motor imagery shares mental representation 2009). This showed that inhibition within M1 was
and mechanism with motor execution (Decety & Ingvar, reduced, which in turn facilitated the corticospinal signal
1990; Di Rienzo et al., 2016; Eaves et al., 2016; O’Shea (Ridding et al., 1995). Cortical mapping, another TMS
& Moran, 2017). These studies found that the activated technique, was used to estimate the cortical (re)organiza-
cortical areas during motor imagery resemble those of tion within M1 during a specific task (Tyc & Boyadjian,
motor planning and motor execution and are predominant 2006). This technique allows generating a TMS map by
in medial SMA, PMA, dorsolateral prefrontal cortex, and measuring and quantifying the intensity and amplitude of
posterior parietal cortex (Decety, 1996; Hanakawa et al., MEPs generated at the target scalp site (Thickbroom
2003; Jeannerod, 2001; Miller et al., 2010). However, et al., 1999). Several studies have used this technique to
the exact role of M1 during motor imagery has been a assess cortical organization within M1 during motor
topic of debate owing to inconsistent findings. For imagery (Bassolino et al., 2014; Marconi et al., 2007;
example, many fMRI studies supported the contribution Vargas et al., 2004). These studies found that motor
of M1 to motor imagery (Lotze et al., 1999; Lotze & imagery and observation increased the map area and map
Halsband, 2006; Porro et al., 1996). However, some volume only for the primary and synergist muscles.
studies could not find any significant activation in M1 Interestingly, Vergeer and Roberts (2006) found that this
(Dechent et al., 2004; Lafleur et al., 2002; Stephan et al., cortical map in M1 was extended compared with rest
1995). In this scenario, NIBS studies proved to be when the posture was compatible with the imagined
important in elucidating the role of M1 in motor movement. The inverse pattern was also true when the
imagery. The role of M1 in motor imagery was sup- posture was not compatible. These findings suggested
ported when the amplitude of MEPs induced by TMS that there is interaction within M1 between the facilita-
over M1 was found to be increased during a motor tory activities of M1 and the proprioceptive inputs

9
S. Bhattacharjee et al.

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