Upper Limb Recovery After Stroke Is Associated With Ipsilesional Primary Motor Cortical Activity: A Meta-Analysis

10 years! What did your competent? doctor do to ensure your ipsilesional primary motor and medial-premotor cortices are functioning correctly? Oh, your doctor DID NOTHING? Well congratulations, you just found out you don't have a functioning stroke doctor! My doctor never bothered to tell me most of my premotor cortex was dead, he knew nothing and did nothing.

Upper Limb Recovery After Stroke Is Associated With Ipsilesional Primary Motor Cortical Activity: A Meta-Analysis

2014, Stroke

sabelle Favre, MD; Thomas A. Zeffiro, MD, PhD; Olivier Detante, MD, PhD; Alexandre Krainik, MD, PhD; Marc Hommel, MD; Assia Jaillard, MD, PhD

Background and Purpos

 

 Although neuroimaging studies have revealed specific patterns of reorganization in the sensorimotor control network after stroke, their role in recovery remains unsettled. To review the existing evidence systematically, we performed activation likelihood estimation meta-analysis of functional neuroimaging studies investigating upper limb movement-related brain activity after stroke. 

  Methods

 

 Twenty-four studies using sensorimotor tasks in standardized coordinates were included, totaling 255 patients and 145 healthy controls. Across the entire brain, we compared task-related activity patterns in good and poor recovery and assessed the magnitude of spatial shifts in sensorimotor activity in cortical motor areas after stroke.  

Results

 

 When compared with healthy controls, patients showed higher activation likelihood estimation values in contralesional primary motor soon after stroke that abated with time, but were not related to motor outcome. The observed activity changes were consistent with restoration of typical interhemispheric balance. In contrast, activation likelihood estimation values in ipsilesional medial-premotor and primary motor cortex were associated with good outcome, reorganization that may reflect vicarious processes associated with ventral activity shifts from BA4a to 4p. In the anterior cerebellum, a novel finding was the association of poor recovery with increased vermal activity, possibly reflecting behaviorally inadequate compensatory strategies engaging the fastigio-thalamo-cortical and corticoreticulospinal systems.  

 

Conclusions

 

Activity in ipsilesional primary motor and medial-premotor cortices in chronic stroke signals good motor recovery, whereas cerebellar vermis activity signals poor recovery. Functional MRI may be useful in identifying recovery biomarkers. (Stroke. 2014;45:1077-1083.) 

Reorganization of Ventral Premotor Cortex After Ischemic Brain Injury: Effects of Forced Use

Since most of my premotor cortex is dead any forced use would fail, so you need to come up with a plan for dead brain recovery. This is just cherry picking low hanging rehab fruit. Solve the difficult problems like leaders do. Are you a leader or a mouse? 

Reorganization of Ventral Premotor Cortex After Ischemic Brain Injury: Effects of Forced Use

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Shawn B. Frost, PhD, Daofen Chen, PhD, Scott Barbay, PhD, ...

First Published May 13, 2022 Research Article Find in PubMed 

https://doi.org/10.1177/15459683221101622

Article information

Abstract

Background

Physical use of the affected upper extremity can have a beneficial effect on motor recovery in people after stroke. Few studies have examined neurological mechanisms underlying the effects of forced use in non-human primates. In particular, the ventral premotor cortex (PMV) has been previously implicated in recovery after injury.

Objective

To examine changes in motor maps in PMV after a period of forced use following ischemic infarct in primary motor cortex (M1).

Methods

Intracortical microstimulation (ICMS) techniques were used to derive motor maps in PMV of four adult squirrel monkeys before and after an experimentally induced ischemic infarct in the M1 distal forelimb area (DFL) in the dominant hemisphere. Monkeys wore a sleeved jacket (generally 24 hrs/day) that forced limb use contralateral to the infarct in tasks requiring skilled digit use. No specific rehabilitative training was provided.

Results

At 3 mos post-infarct, ICMS maps revealed a significant expansion of the DFL representation in PMV relative to pre-infarct baseline (mean = +77.3%; n = 3). Regression analysis revealed that the magnitude of PMV changes was largely driven by M1 lesion size, with a modest effect of forced use. One additional monkey examined after ∼18 months of forced use demonstrated a 201.7% increase, unprecedented in non-human primate studies.

Conclusions

Functional reorganization in PMV following an ischemic infarct in the M1 DFL is primarily driven by M1 lesion size. Additional expansion occurs in PMV with extremely long periods of forced use but such extended constraint is not considered clinically feasible.

Keywords

motor cortex, primary, premotor cortex, stroke rehabilitation

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Study Reveals Set of Brain Regions That Control Complex Sequences of Movement

 I had to figure out on my own that a good chunk of my premotor cortex was dead when I got an MRI scan as part of a research project, correlating the dead area with pictures of brain regions. My doctor did nothing and told me nothing, didn't even tell me I had a stroke, I had a CVA instead, which I had to ask what that was. I was left in the dark on everything about my stroke. One other doctor when I asked how to recover premotor abilities just told me to do some exercises. Totally fucking worthless crapola from him.

Study Reveals Set of Brain Regions That Control Complex Sequences of Movement

 

Summary: The primary motor and primary somatosensory areas of the brain are involved in controlling immediate motor movements in real-time, while the premotor area appears to control planned, sequential movements as well as reacting to and adjusting the sequence when faced with unexpected changes.

Source: Johns Hopkins Medicine

In a novel set of experiments with mice trained to do a sequence of movements and “change course” at the spur of the moment, Johns Hopkins scientists report they have identified areas of the animals’ brains that interact to control the ability to perform complex, sequential movements, as well as to help the mice rebound when their movements are interrupted without warning.

The research, they say, could one day help scientists find ways to target those regions in people and restore motor function caused by injury or illness.

Results of the Johns Hopkins-led experiments were published March 9 in Nature.

Based on brain activity measurements of the specially trained rodents, the investigators found that three main areas of the cortex have distinct roles in how the mice navigate through a sequence of movements: the premotor, primary motor and primary somatosensory areas.

All are on the top layers of the mammals’ brains and arranged in a fundamentally similar fashion in people.

The team concluded that the primary motor and primary somatosensory areas are involved in controlling the immediate movements of the mice in real time, while the premotor area appears to control an entire planned sequence of movements, as well as how the mice react and adjust when the sequence is unexpectedly disrupted.

As the animals perform sequential movements, the researchers say, it’s likely that the premotor area sends electrical signals via special nerve cells to the two other sensorimotor cortex areas, and more studies are planned to chart the paths of those signals between and among the cortical layers.

“Whether it’s an Olympian practicing a downhill ski run or a person doing an everyday chore such as driving, many tasks involve learned sequences of movements made over and over,” says Daniel O’Connor, Ph.D., associate professor of neuroscience at the Johns Hopkins University School of Medicine. O’Connor led the research team.

Such sequential movements may seem commonplace and simple, he says, but they involve complex organization and control in the brain, and the brain must not only direct each movement correctly but also organize them into an entire series of linked movements.

When unexpected things happen to interrupt an ongoing sequence, O’Connor says, the brain must adapt and direct the body to re-configure the sequence in real time. Failure of this process can result in disaster — a fall or car accident, for example.

Neuroscientists have long studied how mammals compensate when an individual movement — such as reaching for a coffee cup — is disrupted, but the new study was designed to address the challenges of tracking what happens when complex sequences of several movements must be reorganized in real time to compensate for unexpected events.

In the case of the Olympic skier, for example, the skier expects to perform a planned series of movements to approach and pass through gates along a downhill run, but there will likely be moments when an obstacle disrupts the skier’s trajectory and forces a change of course.

“How the mammalian brain can take a sensory cue and, almost instantly, use it to completely switch from one ongoing sequence of movements to another remains largely a mystery.” O’Connor worked with Duo Xu, Ph.D., a former graduate student in O’Connor’s laboratory, to design a set of experiments in mice to track the brain regions that process the “change course” cue.

For the study, the researchers first created a “course” for mice that were trained to stick out their tongues and touch a “port” — a metal tube. When the investigators moved the port, the mice learned to touch the port again. Over the span of the course, when the port was moved to its final location, the mice that touched it with their tongues got a reward. All of this training was meant to simulate a repeated and expected sequence of learned movements, much as the skier’s downhill run.

To study how an unexpected cue can prompt the brain to change course, the researchers had the mice perform what scientists call a “backtracking trial.” Instead of moving the port to the next in-sequence location, the researchers moved the port to an earlier location, so that when the mice extended their tongues, they failed to find the port, prompting them to reverse course, find the port, and progress through the course to get the treat.

“Each sequence of port licks involves a series of complex movements that the mouse’s brain needs to organize into a movement plan and then perform correctly, but also to rapidly reorganize when they find that the expected port isn’t there,” says O’Connor.

During the experiments, the researchers used brain electrodes to track and record electrical signals among neurons in the sensorimotor cortex, which controls overall movement. An increase in electrical activity corresponds to increased brain activity.

 

The team concluded that the primary motor and primary somatosensory areas are involved in controlling the immediate movements of the mice in real time, while the premotor area appears to control an entire planned sequence of movements, as well as how the mice react and adjust when the sequence is unexpectedly disrupted. Image is in the public domain

Because many areas of the cortex could be activated when the mice moved through the course in the experiment, the researchers used mice bred with genetically engineered brain cells that, in certain parts of the cortex, can be selectively “silenced” or deactivated. Thus, the scientists could narrow down the location of brain areas directly involved in the movements.

“The results provide a new picture of how a hierarchy among neural networks in the sensorimotor cortex are managing sequential movements,” says O’Connor. “The more we learn about these interacting neural networks, the better positioned we are to understand sensorimotor dysfunction in humans and how to correct it.”

Reorganization of the human ipsilesional premotor cortex after stroke

If something was useful for survivors in here, I missed it.

Reorganization of the human ipsilesional premotor cortex after stroke

Esteban A. Fridman, Takashi Hanakawa, Melissa Chung, Friedhelm Hummel, Ramon C. Leiguarda, Leonardo G. Cohen

Brain, Volume 127, Issue 4, April 2004, Pages 747–758, https://doi.org/10.1093/brain/awh082

Published:

01 April 2004

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Abstract

The substrates that mediate recovery of motor function after stroke are incompletely understood. Several primate and human studies proposed the involvement of the premotor cortex of the lesioned hemisphere. Here, we studied four chronic stroke patients with focal subcortical lesions affecting the corticospinal outflow originating in the primary motor cortex (M1) and good motor recovery. We tested the hypothesis that, in these patients, disruption of activity in the premotor cortex of the lesioned hemisphere by transcranial magnetic stimulation (TMS) would result in degraded behaviour in the paretic hand. TMS was applied to the primary motor cortex, dorsal premotor cortex (PMd) and ventral premotor cortex (PMv) of the affected (M1_AH, PMd_AH, PMv_AH) and intact (M1_IH, PMd_IH, PMv_IH) hemispheres of patients and healthy controls in the setting of a simple reaction time (SRT) paradigm performed with the hand contralateral to the stimulated hemisphere. TMS applied to M1 led to substantial contralateral SRT delays in both groups. TMS applied to PMd_AH of patients elicited clear delays in contralateral SRT in the paretic hand, whereas TMS applied to PMd_IH of patients or healthy volunteers did not. Motor evoked potentials after stimulation of PMd_AH were, on average, larger and had, on average, shorter latency than after stimulation of M1_AH. These results indicate that PMd_AH participates as a substrate mediating functional recovery of executive motor function in patients with focal lesions of corticospinal outflow originating in M1 and good motor recovery. Our results are consistent with the hypothesis that the dorsal premotor cortex of the affected hemisphere can reorganize to control basic parameters of movement usually assigned to M1 function.

 

 

Reorganization of the human ipsilesional premotor cortex after stroke

 

In my case since most of my premotor cortex is dead there can be no transfer from prefrontal to premotor.  I had to figure out what died in my brain by myself since my useless doctor told me nothing on diagnosis or rehab.

Reorganization of the human ipsilesional premotor cortex after stroke

Esteban A. Fridman, Takashi Hanakawa, Melissa Chung, Friedhelm Hummel, Ramon C. Leiguarda, Leonardo G. Cohen

Brain, Volume 127, Issue 4, April 2004, Pages 747–758, https://doi.org/10.1093/brain/awh082

Published:

01 April 2004

Article history

• PDF
• Split View
• Cite
• Permissions Icon Permissions
• Share

Abstract

The substrates that mediate recovery of motor function after stroke are incompletely understood. Several primate and human studies proposed the involvement of the premotor cortex of the lesioned hemisphere. Here, we studied four chronic stroke patients with focal subcortical lesions affecting the corticospinal outflow originating in the primary motor cortex (M1) and good motor recovery. We tested the hypothesis that, in these patients, disruption of activity in the premotor cortex of the lesioned hemisphere by transcranial magnetic stimulation (TMS) would result in degraded behaviour in the paretic hand. TMS was applied to the primary motor cortex, dorsal premotor cortex (PMd) and ventral premotor cortex (PMv) of the affected (M1_AH, PMd_AH, PMv_AH) and intact (M1_IH, PMd_IH, PMv_IH) hemispheres of patients and healthy controls in the setting of a simple reaction time (SRT) paradigm performed with the hand contralateral to the stimulated hemisphere. TMS applied to M1 led to substantial contralateral SRT delays in both groups. TMS applied to PMd_AH of patients elicited clear delays in contralateral SRT in the paretic hand, whereas TMS applied to PMd_IH of patients or healthy volunteers did not. Motor evoked potentials after stimulation of PMd_AH were, on average, larger and had, on average, shorter latency than after stimulation of M1_AH. These results indicate that PMd_AH participates as a substrate mediating functional recovery of executive motor function in patients with focal lesions of corticospinal outflow originating in M1 and good motor recovery. Our results are consistent with the hypothesis that the dorsal premotor cortex of the affected hemisphere can reorganize to control basic parameters of movement usually assigned to M1 function.

 

 

Clinically Significant Gains in Skillful Grasp Coordination by an Individual With Tetraplegia Using an Implanted Brain-Computer Interface With Forearm Transcutaneous Muscle Stimulation

But I would need to know where they are reading the brain signals from. From the forearm it seems, so not applicable to most stroke survivors unless they get the signals directly from the brain. Motor cortex? Pre-motor cortex? Executive control? Both my motor cortex and premotor cortex are heavily dead or damaged. Of course my doctor didn't tell me that, I got that from a research MRI scan.  But I bet with enough training I could use my good motor cortex to send those signals.

Clinically Significant Gains in Skillful Grasp Coordination by an Individual With Tetraplegia Using an Implanted Brain-Computer Interface With Forearm Transcutaneous Muscle Stimulation

Presented to the American Congress of Rehabilitation Medicine (November 2016; Chicago, IL); American Academy of Physical Medicine and Rehabilitation (October 2016, New Orleans, LA); Association of Academic Physiatrists (February 2018; Atlanta, GA; Society for Neuroscience (November 2017; Washington, DC); and Institute of Electrical and Electronics Engineers Engineering in Medicine and Biology (June 2018; Honolulu, HI).

Author links open overlay panelMarcieBockbraderMD, PhD^abc

^∗

NicholasAnnettaMS^dDavidFriedenbergPhD^dMichaelSchwemmerPhD^dNicholasSkomrockMAS^dSamuelColachisIVMS^acdMingmingZhangPhD^dChadBoutonMS^dAliRezaiMD^bGauravSharmaPhD^d∗Walter J.MysiwMD^ab

https://doi.org/10.1016/j.apmr.2018.07.445Get rights and content

Under a Creative Commons license

open access

Highlights

•

A man with paralysis regained hand grasp through BCI-controlled arm muscle stimulation.

•

The device enabled the patient to twist and pour using lateral, palmar, and tip-to-tip grips.

•

Grips for training objects carried over successfully to novel objects and tasks.

•

The patient’s functional motor level improved when using the BCI from C5-6 to C7-T1.

•

Translation to home use could decrease dependence for activities of daily living.

Abstract

Objective

To demonstrate naturalistic motor control speed, coordinated grasp, and carryover from trained to novel objects by an individual with tetraplegia using a brain-computer interface (BCI)-controlled neuroprosthetic.

Design

Phase I trial for an intracortical BCI integrated with forearm functional electrical stimulation (FES). Data reported span postimplant days 137 to 1478.

Setting

Tertiary care outpatient rehabilitation center.

Participant

A 27-year-old man with C5 class A (on the American Spinal Injury Association Impairment Scale) traumatic spinal cord injury

Interventions

After array implantation in his left (dominant) motor cortex, the participant trained with BCI-FES to control dynamic, coordinated forearm, wrist, and hand movements.

Main Outcome Measures

Performance on standardized tests of arm motor ability (Graded Redefined Assessment of Strength, Sensibility, and Prehension [GRASSP], Action Research Arm Test [ARAT], Grasp and Release Test [GRT], Box and Block Test), grip myometry, and functional activity measures (Capabilities of Upper Extremity Test [CUE-T], Quadriplegia Index of Function-Short Form [QIF-SF], Spinal Cord Independence Measure–Self-Report [SCIM-SR]) with and without the BCI-FES.

Results

With BCI-FES, scores improved from baseline on the following: Grip force (2.9 kg); ARAT cup, cylinders, ball, bar, and blocks; GRT can, fork, peg, weight, and tape; GRASSP strength and prehension (unscrewing lids, pouring from a bottle, transferring pegs); and CUE-T wrist and hand skills. QIF-SF and SCIM-SR eating, grooming, and toileting activities were expected to improve with home use of BCI-FES. Pincer grips and mobility were unaffected. BCI-FES grip skills enabled the participant to play an adapted “Battleship” game and manipulate household objects.

Conclusions

Using BCI-FES, the participant performed skillful and coordinated grasps and made clinically significant gains in tests of upper limb function. Practice generalized from training objects to household items and leisure activities. Motor ability improved for palmar, lateral, and tip-to-tip grips. The expects eventual home use to confer greater independence for activities of daily living, consistent with observed neurologic level gains from C5-6 to C7-T1. This marks a critical translational step toward clinical viability for BCI neuroprosthetics.

Graphical Abstract

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• 
  

Keywords

Activities of daily living

Brain-computer interfaces

Hand strength

Quadriplegia

Rehabilitation

Transcutaneous electric nerve stimulation

List of abbreviations

ARAT

Action Research Arm Test

BBT

Box and Block Test

BCI

brain-computer interface

CUE-T

Capabilities of Upper Extremity Test

FES

functional electrical stimulation

GAIN

Generalizability, Ability, Independence, Neurologic Level

GRASSP

Graded Redefined Assessment of Strength, Sensibility, and Prehension

GRT

Grasp and Release Test

MEA

microelectrode array

MMT

manual muscle training

QIF-SF

Quadriplegia Index of Function-Short Form

SCI

spinal cord injury

SCIM-SR

Spinal Cord Independence Measure–Self-Report

SRD

smallest real difference

Individuals with tetraplegia prioritize recovery of upper limb strength and dexterity to facilitate their independence.1, 2, 3, 4, 5 Voluntary control of hand grasp has been restored to paralyzed limbs using noninvasive6, 7, 8, 9, 10, 11 and cortical microelectrode array (MEA)-based12, 13, 14, 15, 16 brain-computer interfaces (BCIs) that translate brain activity to hand movements evoked through implanted10, 11, 12 or transcutaneous6, 7, 8, 9, 13, 14, 15, 16 functional electrical stimulation (FES).6, 7, 8, 9, 12, 13 However, clinically significant gains on tests of upper limb function have not been demonstrated using BCI-FES. The critical translational path for BCI neuroprosthetics requires demonstration of clinically meaningful gains in speed, dexterity, and smooth integration of grip with other arm movements to perform complex tasks.

Our goal was to evaluate whether an individual with tetraplegia could make clinically significant gains in skillful grasp coordination17, 18 using an investigational MEA-BCI-FES. We formulated a framework¹⁹ called Generalizability, Ability, Independence, Neurologic Level (GAIN) that reflects design goals for BCI neuroprosthetics to assist in this assessment. GAIN was inspired by end-user perspectives,4, 20, 21 challenges to translation,22, 23 and clinical evaluations developed for surgical interventions for tetraplegia.²⁴ We anticipate it being useful for comparing performance across neuroprosthetic technologies and justifying (eg, to regulatory or payer sources) that a device measurably improves function on the International Classification of Functioning, Disability, and Health domains recognized by the World Health Organization.²⁵

Devices meeting the GAIN standard include the following: (1) demonstrate generalizability, defined as performing well without retraining for objects with similar grip features (e.g., lateral, tip-to-tip, palmar, pincer grasps); (2) confer clinically significant gains in motor ability on standardized, psychometrically validated, and expert-endorsed24, 26, 27, 28, 29, 30, 31, 32, 33 tests of upper limb function; (3) affect daily life by facilitating functional independence for activities of daily living (ADLs) on psychometrically validated assessments24, 26, 27, 28, 29, 30, 31, 32, 33; and (4) improve the user’s neurologic level of function on validated measures normed to the International Standards for the Neurological Classification of Spinal Cord Injury standards.³⁴

Methods

This was a Phase I trial of a MEA-BCI interfaced with the Neurolife^a transcutaneous, forearm FES. Like similar intracortical BCI studies,12, 13, 14, 15, 16, 17, 18, 35, 36 this report was limited to 1 participant, the first to use the system, due to the invasive nature of the investigational brain implant and time required for training and assessment. Technical BCI-FES features13, 37 (fig 1), the Utah Array^b MEA implantation procedures, and machine learning algorithms used to generate decoders were described previously. The participant provided written informed consent as approved by our local institutional review board.

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Motor and Premotor Cortices in Subcortical Stroke: Proton Magnetic Resonance Spectroscopy Measures and Arm Motor Impairment

Something might be important in here but with all the big words I got nothing out of it.

Motor and Premotor Cortices in Subcortical Stroke: Proton Magnetic Resonance Spectroscopy Measures and Arm Motor Impairment 

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Sorin C. Craciunas, MD, PhD, William M. Brooks, PhD, Randolph J. Nudo, PhD,

First Published January 8, 2013 Research Article Find in PubMed 

https://doi.org/10.1177/1545968312469835

Article information

Abstract

Background. 

Although functional imaging and neurophysiological approaches reveal alterations in motor and premotor areas after stroke, insights into neurobiological events underlying these alterations are limited in human studies.  

Objective. 

We tested whether cerebral metabolites related to neuronal and glial compartments are altered in the hand representation in bilateral motor and premotor areas and correlated with distal and proximal arm motor impairment in hemiparetic persons.  

Methods. 

In 20 participants at >6 months postonset of a subcortical ischemic stroke and 16 age- and sex-matched healthy controls, the concentrations of N-acetylaspartate and myo-inositol were quantified by proton magnetic resonance spectroscopy. Regions of interest identified by functional magnetic resonance imaging included primary (M1), dorsal premotor (PMd), and supplementary (SMA) motor areas. Relationships between metabolite concentrations and distal (hand) and proximal (shoulder/elbow) motor impairment using Fugl-Meyer Upper Extremity (FMUE) subscores were explored.  

Results. 

N-Acetylaspartate was lower in M1 (P = .04) and SMA (P = .004) and myo-inositol was higher in M1 (P = .003) and PMd (P = .03) in the injured (ipsilesional) hemisphere after stroke compared with the left hemisphere in controls. N-Acetylaspartate in ipsilesional M1 was positively correlated with hand FMUE subscores (P = .04). Significant positive correlations were also found between N-acetylaspartate in ipsilesional M1, PMd, and SMA and in contralesional M1 and shoulder/elbow FMUE subscores (P = .02, .01, .02, and .02, respectively).  

Conclusions. 

 Our preliminary results demonstrated that proton magnetic resonance spectroscopy is a sensitive method to quantify relevant neuronal changes in spared motor cortex after stroke and consequently increase our knowledge of the factors leading from these changes to arm motor impairment.

Keywords subcortical stroke, motor and premotor cortices, proton magnetic resonance spectroscopy, distal and proximal arm motor impairment

Introduction

Human imaging studies have revealed that early after subcortical stroke, restoration of paretic arm function is associated with a greater involvement of radiologically normal-appearing (or spared) motor (primary motor cortex or M1) and premotor (dorsal premotor cortex or PMd, supplementary motor area or SMA) areas in both injured (ipsilesional) and uninjured (contralesional) hemispheres.^1-3 Later, successful recovery occurs in stroke survivors who exhibit relatively normal patterns of ipsilesional activation and less contralesional motor activation, whereas patients, who often show bilateral cortical activation, typically have less complete recovery.^4-6 These results should be viewed in the context of the anatomic structures and pathways of these areas. Although M1 motor pathways are critical, the premotor areas also contribute to motor control and might be recruited during motor recovery after stroke. The parallel nature of the direct (corticospinal) pathways from premotor areas and M1 emphasizes that PMd and SMA are, in some respects, at a similar level of hierarchical organization as M1,⁷ although these projections to spinal cord motor neurons are less numerous and less efficient than those from M1.^8-10 Another possibility is the indirect (corticoreticulospinal) projections to cervical propriospinal premotoneurons, which have divergent projections to muscle groups operating at multiple joints.^11,12 Finally, corticocortical connections between these areas might also play an important role in poststroke recovery.^7,13-15 Thus, understanding the neural events associated with the functional changes in these areas could provide critical insight into successful treatments of patient’s impairment.

Proton magnetic resonance spectroscopy (¹H-MRS) provides a noninvasive means to measure concentrations of certain metabolites associated with a specific cell type¹⁶ after stroke.¹⁷ Most clinical stroke studies report lower levels of N-acetylaspartate (NAA, putative marker of neuronal integrity) in spared ipsilesional M1 and PMd.^18-21 In some instances, the NAA levels were related to clinical severity. In a series of studies of stroke survivors, we also found higher myo-inositol (mI, putative marker of glial cells) in ipsilesional and contralesional M1.²¹ However, none of these studies addressed the changes in key metabolites related to neuronal and glial compartments, that is, NAA and mI, in motor and premotor areas in stroke.

The first aim of the current study was to quantify NAA and mI concentrations in ipsilesional and contralesional motor and premotor areas in chronic subcortical stroke. Since neuronal integrity might be compromised in these remote areas,^21,22 we expected NAA to be lower, especially in the ipsilesional areas. Given the role of glia in plastic brain changes,^23-25 we also expected mI to be higher. The second aim was to explore correlations between metabolite concentrations and arm motor impairment. Since the premotor projections are significantly stronger on the proximal muscles than distal muscles compared with M1^8,9, we predicted that metabolite measures in ipsilesional PMd and SMA would be correlated with proximal (shoulder/elbow) motor impairment whereas those in M1 would be correlated with both proximal and distal (hand) impairments. Since both direct and indirect pathways from the contralesional M1 project to axial and proximal muscles rather than hand muscles,^26,27 relationships between contralesional M1 metabolites and proximal impairment were also expected.

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Targeted engagement of a dorsal premotor circuit in the treatment of post-stroke paresis

Good luck figuring out what a premotor therapy is and you need robotics besides. I believe most of my premotor cortex was destroyed so nothing here will help me even if I could figure it out. 

Targeted engagement of a dorsal premotor circuit in the treatment of post-stroke paresis

2013, NeuroRehabilitation
 Lucy Dodakian a, 

Kelli G. Sharp a, 

Jill See a, 

Neil S. Abidi a, 

Khoa Mai a, 

Brett W. Fling a, 

Vu H. Le a

and Steven C. Cramer a,b,∗
a  Department of Anatomy & Neurobiology, University of California, Irvine, CA, USA
b  Department of Neurology, University of California, Irvine, CA, USA

*  Address for correspondence: Steven C. Cramer, MD, University of California, Irvine Medical Center, 200S. Manchester Ave. Suite206, Orange, CA 92868, USA. Tel.: +1 714 456 6876; Fax: +1 714456 8805; E-mail: scramer@uci.edu

Abstract

.
BACKGROUND:
 Good motor outcome after stroke has been found to correlate with increased activity in a dorsal premotor(PMd) brain circuit, suggesting that therapeutic strategies targeting this circuit might have a favorable, causal influence on motor status.
OBJECTIVE:
This study addressed the hypothesis that a Premotor Therapy that exercises normal PMd functions would providegreater behavioral gains than would standard Motor Therapy; and that Premotor Therapy benefits would be greatest in patients with greater preservation of PMd circuit elements.
METHODS:
 Patients with chronic hemiparetic stroke (n=15) were randomized to 2-weeks of  Premotor Therapy
 or Motor Therapy, implemented through a robotic device.
RESULTS:
 Overall, gains were modest but significant (change in FM score, 2.1±2.8 points, p<0.02) and did not differ by treatment assignment. However, a difference between Therapies was apparent when injury to the PMd circuit was considered, as the interaction between treatment assignment and degree of corticospinal tract injury was significantly related to the change inFM score (p=0.018): the more the corticospinal tract was spared, the greater the gains provided by Premotor Therapy. Similar results were obtained when looking at the interaction between treatment assignment and PMd function (p=0.03).
CONCLUSIONS:
 Targeted engagement of a brain circuit is a feasible strategy for stroke rehabilitation. This approach has maximum impact when there is less stroke injury to key elements of the targeted circuit.Keywords: Stroke, premotor cortex, robot, motor recovery, corticospinal tract
1. Introduction
Motor deficits are among the most common forms of impairment after stroke, present in>80% of patients acutely (Rathore, Hinn, Cooper, Tyroler, & Rosamond,2002). Most patients show spontaneous improvement in motor status during the weeks following stroke. Several forms of brain plasticity that contribute to this recovery have been identified (S. C. Cramer, 2008;Nudo, 2011). In particular, anatomical and functional evidence support a role for dorsal premotor cortex in support of return of motor function (Alagona et al.,2001; S. Cramer et al., 1997; Denny-Brown, 1950;Fries, Danek, Scheidtmann, & Hamburger, 1993; Gau-thier, Taub, Mark, Barghi, & Uswatte, 2012; Laplane,Talairach, Meininger, Bancaud, & Bouchareine, 1977;Seitz et al., 1998; Weiller, Chollet, Friston, Wise, &Frackowiak, 1992). Activity within ipsilesional dorsal premotor cortex (PMd) has been associated withachieving spontaneous recovery (Fridman et al., 2004;Platz et al., 2000; Rehme, Eickhoff, Wang, Fink, &Grefkes, 2011; Sharma, Baron, & Rowe, 2009; Wardet al., 2006) as well as treatment-induced recovery(Careyetal.,2002;Johansen-Berg,Dawes,etal.,2002;
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 L. Dodakian et al. / Targeted dorsal premotor engagement
Page,Szaflarski,Eliassen,Pan,&Cramer,2009;Strup-pler et al., 2007) after stroke. Evidence suggests that contralesional PMd might contribute to recovery, too,particularly in patients with more severe stroke (Bute-fisch et al., 2005; Kantak, Stinear, Buch, & Cohen,2012; Lotze et al., 2011; Rehme, Fink, von Cramon,&Grefkes,2011).Changes in PMd activity are thought to support behavioral gains through connections with ipsilesional primary motor cortex (M1), contralesional brain areas, spinal cord targets, and possibly reticulospinal brain stem neurons (Fregni & Pascual-Leone,2006; Fridman, et al., 2004; James et al., 2009; Kantak, et al., 2012). Together, these findings suggest that therapies that increase PMd activity could improve motor status after stroke. This idea was examined in the current study by testing two main hypotheses. The first is that practicing a motor behavior known to engage PMd circuitry will improve motor status after stroke to a greater extent than will practicing a repetitive motor behavior unrelated to PMd. These cond is that the extent to which such a PMd-based therapy provides superior gains in motor status will vary with the availability of PMd anatomically, and perhaps functionally–a therapy can not provide benefit if its biological target is excessively injured by stroke(Nouri & Cramer, 2011). These two hypotheses were examined in the cur-rent study, with a focus on the distal upper extremity. A Premotor Therapy
 was designed, the features of which emphasized normal functions of a PMd circuit.Key anatomical components of the PMd circuit include PMd, which processes novel external cues in order to guide the timing and the choice of voluntary movements(Askim,Indredavik,&Haberg,2010;Chouinard&Paus,2006;Geyer,Matelli,Luppino,&Zilles,2000;Koch et al., 2006; Kurata & Hoffman, 1994; O’Shea,Johansen-Berg,Trief,Gobel,&Rushworth,2007;Pass-ingham, 1993; Rushworth, Johansen-Berg, Gobel, &Devlin, 2003; Schluter, Rushworth, Passingham, &Mills, 1998), as well as M1 and the corticospinaltract, important for expressing the output of corticalcomponents of the circuit. A study of healthy control subjects (described below) confirmed that performing the timed movement tasks that constitute Premotor Therapy
 was associated with increased activity within a dorsal premotor circuit. A robotic device (Takahashi,Der-Yeghiaian, Le, Motiwala, & Cramer, 2008), found to improve post-stroke arm motor function in a prior study, served as an ideal vehicle for implementing the timed cues central to
 Premotor Therapy, and furthermore allowed inclusion of therapy in a gaming context, an approach useful to modulating the function of selected brain circuits (Bavelier, Levi, Li, Dan, &Hensch, 2010; Colzato, van den Wildenberg, Zmigrod,& Hommel, 2012). In the current study, this Premotor Therapy
 was contrasted with Motor Therapy
, in which subjects performed the same distal arm movements as with
 Premotor Therapy but without cues or novelty. Patients with chronic stroke underwent a baseline example plus MRI for assessing anatomical and functional features of a PMd circuit, were randomized to two weeks of Motor Therapy vs. Premotor Therapy via the robotic device, and then had their motor outcome assessed 1 month after completion of therapy. These data were used to address the above two hypotheses.