Editorial Interventions to Enhance Adaptive Plasticity ...downloads.hindawi.com/journals/np/2016/9153501.pdf · Interventions to Enhance Adaptive Plasticity after Stroke: From Mechanisms

EditorialInterventions to Enhance Adaptive Plasticity after Stroke:From Mechanisms to Therapeutic Perspectives

Adriana Conforto,1,2 Annette Sterr,3 Ela Plow,4 and Leonardo Cohen5

1Neurology Clinical Division, Neurology Department, Hospital das Clinicas, Sao Paulo University, 05508-090 Sao Paulo, SP, Brazil2Hospital Israelita Albert Einstein, 05652-900 Sao Paulo, SP, Brazil3Department of Psychology, University of Surrey, Guildford, Surrey GU2 7XH, UK4Center for Neurological Restoration, Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland Clinic Foundation, Cleveland,OH 44195, USA5Human Cortical Physiology and Stroke Neurorehabilitation Section, National Institute of Neurological Disorders and Stroke, NIH,Bethesda, MD 20892, USA

Correspondence should be addressed to Adriana Conforto; [email protected]

Received 16 May 2016; Accepted 24 May 2016

Copyright © 2016 Adriana Conforto et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Disability from stroke represents a great burden worldwide.The science of stroke rehabilitation flourished in the lastdecades, as the concept of brain plasticity advanced. It isnow known that the adult brain can rewire in response toexperience and training in healthy subjects and in diseasestates such as stroke. However, there is a gap between plastic-ity studies in animals demonstrating “rewiring” of neuronalcircuits and the availability of neurorehabilitative strategiesin the clinical domain. Although mechanisms underlyingrecovery are not completely understood, there is some evi-dence to suggest that recovery at least entails resolutionof acute tissue damage and behavioral compensation, aswell as functional and structural changes. There is evidencethat better outcomes are associated with the greatest returnof brain function toward the normal state of organizationbefore stroke. How to drive adaptive reorganization remainsan open question. In this special issue, five manuscriptsaddress questions related to interventions that aim to enhanceadaptive plasticity after stroke. How do we capitalize onmechanisms of plasticity to develop effective therapeuticapproaches? How do we individualize therapy in such aheterogeneous condition as stroke?

Over the past decades, the interest in the potential useof brain stimulation to boost adaptive plasticity and enhancemotor and language functions has steadily grown. Accordingto one of the hypotheses of recovery after stroke, increased

activity of the unaffected hemisphere and decreased activityof the affected hemisphere can be detrimental to motor andlanguage performance. In this special issue, J. C. Griffis etal. assessed the effects of ten sessions of neuronavigatedintermittent theta-burst stimulation (iTBS) given to residualleft inferior frontal gyrus (IFG) in four patients with anomicaphasia and four patients with Broca’s aphasia, in the chronicphase after left-hemisphere strokes.They intended to upregu-late activity in the left IFG and decrease possibly detrimentalhyperactivity in the right IFG. They went a step furtherand evaluated changes in connectivity between the rightand left IFG after this intervention. Indeed, they observed ashift in the functional magnetic resonance imaging (fMRI)lateralization of IFG during a covert verb generation taskafter iTBS, as well as a decrease in connectivity between rightand left IFG after treatment. Even though these preliminaryresults from a pilot, open-label study appear to be promising,larger, sham-controlled trials of iTBS are needed. A challengein designing such trials is to define selection criteria thatwould help identify patients with the greatest likelihoodof showing clinically meaningful improvements with brainstimulation treatment.

E. B. Plow et al. have suggested ways to address thischallenge in the next manuscript. They have explained howone can personalize brain stimulation to improve motoroutcomes for both patients with mild as well as patients

Hindawi Publishing CorporationNeural PlasticityVolume 2016, Article ID 9153501, 2 pageshttp://dx.doi.org/10.1155/2016/9153501

2 Neural Plasticity

with severe upper limb paresis. A model of individual-ized interventions that tailor treatments to each patient isproposed. The idea is to stratify paradigms of stimulationaccording tomechanisms underlying plasticity. Upregulationof excitability of the affected hemisphere and downregulationof excitability of the unaffected hemisphere according tothe model of interhemispheric inhibition are not alwaysbeneficial. Therefore, strategies to match the right strategyto the right patient according to baseline level of severity ofdamage andparesis aswell as structural or functional imagingwere discussed. While emphasis of their discussion was onimproving motor function, E. B. Plow et al. also discussedstudies that extended the idea of tailoring interventions totreat language andmood disorders.The need to devise thera-pies that can decrease the burden of stroke in mildly affectedpatients, but especially in those with severe impairments,was highlighted. Still, models discussed in this manuscripthave largely been theoretical; empirical investigations to testeffectiveness of many models are still underway.

In a different manuscript, L. Furlan et al. reviewedstudies that contributed to unveil the neural correlates ofeffects of upper limb immobilization and proposed thatthis intervention could be a valuable tool to develop novelstrategies for patients with poor upper limb performance.Upper limb immobilization is one of the components ofthe original constraint-induced movement therapy (CMIT)protocol for stroke. CMIT has emerged as an evidence-basedintervention to improve use of the paretic arm in relativelyhigh-functioning subjects with stroke. This intervention hasnot yet been proven to benefit low-functioning patients, whopresent deep nonuse of the affected upper limb. However,upper limb immobilization can be employed as a model oflow-functioning upper limb paresis and hence help to under-stand mechanisms underlying poor upper limp function, aswell as refining treatments that can enhance outcomes inseverely affected patients. Testing effects of motor imagery,action observation, peripheral somatosensory stimulation,and brain stimulation in the context of upper limb immobi-lization could advance the neurobehavioral framework andfoster fine tunings in rehabilitation paradigms in order topotentiate adaptive plasticity as well as motor gains in thesepatients.

Similar to the notions suggested in manuscripts by J.C. Griffis et al. and E. B. Plow et al., where knowledgeof mechanisms of plasticity is believed to be elementalto help match the right patient to the right treatment,M. Gandolla et al. investigated mechanisms of functionalelectrical stimulation (FES) treatment for foot drop in orderto predict responsiveness to treatment. Some patients canrelearn the ability to dorsiflex the ankle after finishing onemonth of gait rehabilitation aided by FES of the tibialisanterior muscle (“carryover”) while others cannot. The studyaimed to evaluate mechanisms of the FES carryover effect bycomparing differences in brain activity before FES treatment,in patients who presented a carryover effect, in patients whodid not present this effect after treatment, and in controlswithout stroke, who did not undergo treatment. Brain areasof investigation were chosen based on previous knowledgeabout mechanisms underlying sensorimotor integration and

voluntary movement. The authors were able to separatepatients who evolved with and without a FES carryover effectafter treatment, based on brain responses in the contralat-eral supplementary motor area (SMA) and angular gyrus.Furthermore, patients with a carryover effect, but not thosewithout, had responses in SMA and in the primary motorcortex that were similar to those found in healthy controls.This manuscript is an example of how to translate data aboutmechanisms underlying plasticity into information that canbe clinically useful, for instance, to help selecting patientsin future trials in order to maximize potential treatmentbenefits. It also suggests that central plasticity can be inducedby manipulating afferent input at the periphery, in line withother studies.

Another manuscript that evaluated effects of a peripheralintervention based on augmentation of somatosensory inputin order to drive central motor plasticity was authored by C.Garcia et al. The authors applied electric currents to the skinoverlying forearm muscles at four different frequencies in upto fourteen healthy subjects, for 5 minutes or 30 minutes. Nochanges in amplitudes of motor evoked potentials (MEPs),and no changes in H-reflexes were observed. The authorsalso studied five patients who had experienced upper limbspasticity in the chronic phase after stroke. Patients received30 minutes of somatosensory stimulation delivered at 3Hz.Again, the intervention failed to elicit changes inMEP ampli-tudes or spasticity tested during the performance of passivemovement of the wrist. The results are very preliminary,considering the sample sizes, but suggest that short periodsof electrical stimulation of the skin overlying forearm flexormuscles may not lead to measurable changes in cortical orspinal excitability or that if such changes occur, they are notcaptured by evaluation of MEPs or H-reflexes. Other periph-eral interventions, such as somatosensory stimulation in theform of peripheral nerve stimulation or muscle vibration,seem more promising.

The articles published in this special issue underscore theimportance of identifying the functional role of specific brainareas as well as brain networks that can assume functioningof lesioned tissue to develop interventions that can improveclinically significant outcomes. Effects of particular interven-tions not only on specific brain areas but also on interactionsbetween areas should be tested in order to bridge the gapbetween animal studies, translational research, and clinicalrehabilitation.

Acknowledgments

Adriana Conforto received funding from the National Insti-tutes of Health (Grant R01NS076348-04). Ela Plow receivedfunding from the National Institutes of Health (GrantK01HD069504) and theAmericanHeart/StrokeAssociation’s(Grants 16GRNT27720019 and 13BGIA17120055).

Adriana ConfortoAnnette Sterr

Ela PlowLeonardo Cohen

Submit your manuscripts athttp://www.hindawi.com

Neurology Research International

Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

Alzheimer’s DiseaseHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

International Journal of

ScientificaHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


BioMed Research International


Research and TreatmentSchizophrenia

The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014


Neural Plasticity


Parkinson’s Disease


Research and TreatmentAutism

Sleep DisordersHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


Neuroscience Journal

Epilepsy Research and TreatmentHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


Psychiatry Journal


Computational and Mathematical Methods in Medicine

Depression Research and TreatmentHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


Brain ScienceInternational Journal of

StrokeResearch and TreatmentHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

Neurodegenerative Diseases


Journal of

Cardiovascular Psychiatry and NeurologyHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

Documents

Editorial Interventions to Enhance Adaptive Plasticity ...downloads.hindawi.com/journals/np/2016/9153501.pdf · Interventions to Enhance Adaptive Plasticity after Stroke: From Mechanisms