Noninvasive Brain Stimulation to Modulate Neuroplasticity in Traumatic Brain Injury

doi:10.1111/j.1525-1403.2012.00474.x

Neuromodulation: Technology at the Neural Interface

Volume 15, Issue 4, August 2012, Pages 326-338

https://doi.org/10.1111/j.1525-1403.2012.00474.x Get rights and content

Objective

To review the use of noninvasive brain stimulation (NBS) as a therapeutic tool to enhance neuroplasticity following traumatic brain injury (TBI).

Materials and Methods

Based on a literature search, we describe the pathophysiological events following TBI and the rationale for the use of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in this setting.

Results

The pathophysiological mechanisms occurring after TBI vary across time and therefore require differential interventions. Theoretically, given the neurophysiological effects of both TMS and tDCS, these tools may: 1) decrease cortical hyperexcitability acutely after TBI; 2) modulate long-term synaptic plasticity as to avoid maladaptive consequences; and 3) combined with physical and behavioral therapy, facilitate cortical reorganization and consolidation of learning in specific neural networks. All of these interventions may help decrease the burden of disabling sequelae after brain injury.

Conclusions

Evidence from animal and human studies reveals the potential benefit of NBS in decreasing the extent of injury and enhancing plastic changes to facilitate learning and recovery of function in lesioned neural tissue. However, this evidence is mainly theoretical at this point. Given safety constraints, studies in TBI patients are necessary to address the role of NBS in this condition as well as to further elucidate its therapeutic effects and define optimal stimulation parameters.

Section snippets

INTRODUCTION

Traumatic brain injury (TBI) is a major health problem with devastating consequences and an enormous socioeconomic burden on individuals and their families. It has been estimated to affect around 1.5 million people in the USA each year, resulting in 290,000 hospitalizations and 51,000 deaths (1), and lifetime costs that may reach $2 million per patient (2). An estimated 5.3 million U.S. citizens live with long-term disabilities following TBI (3). Although cognitive and emotional derangements

ACUTE CHANGES FOLLOWING TBI

TBI has been divided into primary and secondary injury. The former involves the initial disruption of brain tissue by a cortical contusion, hemorrhage, or axonal injury (5), oftentimes causing irreversible damage to the central nervous system (CNS) (6). The secondary injury consists of a series of events that lead to impairment of cell functions, cell death (7), and consequent dissemination of damage (8), which will eventually determine the degree and magnitude of long-term deficits (9). From a

The Role of Brain Plasticity in TBI Recovery

Plasticity can be defined as an ongoing, intrinsic property of the nervous system, whereby changes in the afferent input or the efferent demands of a neural network lead to systemic reorganization that might be demonstrable from molecular and cellular to anatomical and behavioral levels (35). This dynamic process plays a crucial role in neural development and homeostasis (36), as well as in the response after damage to the peripheral or central nervous system. In the setting of brain injury,

Transcranial Magnetic Stimulation (TMS)

TMS, introduced in 1985 (103), is an NBS technique based on the principle of electromagnetic induction. By passing a very brief and large electric current though a coil held over the scalp, a rapidly changing magnetic field is created which then penetrates relatively unimpeded through the skull and secondarily induces electric currents in particular brain regions. When a single TMS pulse is applied, the resulting electric current can be of sufficient magnitude to depolarize cortical neurons,

TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS)

Modification of brain function by means of electrical currents was first described more than 200 years ago (129) and extensively studied in animal models in the 1950s and 1960s (130., 131., 132., 133., 134.). Based on these observations, tDCS was developed as an NBS technique that consists of placing two relatively large rubber electrodes (25–35 cm²) on the scalp, in order to allow a weak direct current to flow from anode to cathode. Although there is shunting of current in the overlying

NBS AS A THERAPEUTIC TOOL IN TBI

TBI may lead to a variety of neurobehavioral consequences that may appear in the first days after the insult and continue to show in the following months (2). These may include seizures (154,155), headache (156), movement disorders, motor impairment, language and visual deficits, sleep (157), memory (158,159), and attention disorders as well as concentration impairment (160). The course of recovery is complex and the time needed to recover from these sequelae may last months to years (2),

SAFETY CONSIDERATIONS

Due to specific characteristics of this group of patients, some particular safety considerations regarding the use of NBS in TBI should be noted. First, given their high incidence of LPTS, one of the potential issues that may arise relates to the likelihood of triggering seizures associated with the stimulation. The other involves the effects of NBS in individuals with skull defects and skull plates, two common findings among TBI survivors.

A large number of subjects and patients have undergone

CONCLUDING REMARKS

The complex pathophysiology underlying TBI, together with the diversity of phenomena that predominate at different time points and the unique characteristics of each patient, make it necessary to develop individualized therapeutic approaches. They would help enhance recovery and decrease the burden of disabling sequelae after the injury.

Plasticity, an innate property of the brain, is responsible for the changes occurring not only in the lesioned site but also in distant areas, and takes place

Acknowledgements

The authors wish to thank Ms. Laura Sherman for her editorial support during preparation of this manuscript, and the reviewers for their insightful feedback and comments.

Authorship Statements

Drs. Villamar and Santos Portilla conducted a review of the literature and prepared the manuscript, with important intellectual input provided by Drs. Zafonte and Fregni. All authors approved the final manuscript.

How to Cite this Article:

Villamar M.F., Santos Portilla A., Fregni F., Zafonte R. 2012. Noninvasive Brain Stimulation to Modulate

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Prior work has shown that the lateral occipital cortex (LO) is involved in recognition of objects and their parts, as well as segregation of that object (or “figure”) from its background. No studies, though, have examined how LO's functioning is influenced by non-invasive brain stimulation, particularly during a figure-ground perception task. The present study tested whether high-definition transcranial direct current stimulation (HD-tDCS) to right LO influences the effects of familiarity on figure-ground perception. Following 20 min of offline anodal stimulation (or sham), participants viewed masked stimuli consisting of two regions separated by a vertical border and were asked to report which region they perceived as figure. One region was the “critical” region, which either depicted a portion of a familiar object (“Familiar” stimuli), or a familiar object with its parts rearranged into a novel configuration (“Part-rearranged” stimuli). Previous research using these stimuli has found higher reports of the critical region as figure for Familiar vs. Part-rearranged displays, demonstrating the effect of familiarity on figure assignment. The results of the current study showed that HD-tDCS to right LO significantly influenced this typical behavioral pattern. Specifically, stimulation (vs. sham) increased reports of the critical region as figure for Part-rearranged stimuli, bringing perception of these displays up to the level of the Familiar stimuli. We interpret this finding as evidence that stimulation of right LO increased participants' reliance on the familiarity of the parts in their figure-ground judgements—a finding consistent with and extending previous research showing that LO is indeed sensitive to object parts. This is the first study showing that HD-tDCS to LO can influence the effects of familiarity on figure-ground perception.
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Editor’s Choice: Review ArticleNoninvasive Brain Stimulation to Modulate Neuroplasticity in Traumatic Brain Injury

Objective

Materials and Methods

Results

Conclusions

Section snippets

INTRODUCTION

ACUTE CHANGES FOLLOWING TBI

The Role of Brain Plasticity in TBI Recovery

Transcranial Magnetic Stimulation (TMS)

TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS)

NBS AS A THERAPEUTIC TOOL IN TBI

SAFETY CONSIDERATIONS

CONCLUDING REMARKS

Acknowledgements

Authorship Statements

How to Cite this Article:

Neurother

PM R

Psychiatr Clin North Am

Prog Brain Res

Neurother

Lancet Neurol

Trends Pharmacol Sci

Drug Discov Today

Neuron

Neurochem Int

Neuron

Prog Brain Res

Curr Opin Neurobiol

Neuron

J Clin Neurosci

Behav Brain Res

Neuroscience

PM R

Clinics

Biol Psychiatry

Prog Brain Res

Lancet

Behav Brain Res

Prog Brain Res

Int Rev Neurobiol

Incidence of traumatic brain injury in the United States, 2003

J Head Trauma Rehabil

Rehabilitation of persons with traumatic brain injury. NIH consensus development panel on rehabilitation of persons with traumatic brain injury

JAMA

Surveillance for traumatic brain injury-related deaths—United States, 1997–2007

MMWR Surveill Summ

Traumatic brain injury in the United States: a public health perspective

J Head Trauma Rehabil

Traumatic brain injury: can the consequences be stopped?

CMAJ

Modeling brain injury/trauma

Pathophysiology of traumatic brain injury

Mt Sinai J Med

Imaging of closed head injury

Radiology

Clinical characteristics and pathophysiological mechanisms of focal and diffuse traumatic brain injury

J Cell Mol Med

Enhancement of AMPA-mediated current after traumatic injury in cortical neurons

J Neurosci

Ultrastructural evidence of axonal shearing as a result of lateral acceleration of the head in non-human primates

Acta Neuropathol

Update of neuropathology and neurological recovery after traumatic brain injury

J Head Trauma Rehabil

Ionic dependence of glutamate neurotoxicity

J Neurosci

mu-calpain activation and calpain-mediated cytoskeletal proteolysis following traumatic brain injury

J Neurochem

A mechanistic analysis of nondisruptive axonal injury: a review

J Neurotrauma

Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates

Hippocampus

Mitochondrial dysfunction and calcium perturbation induced by traumatic brain injury

J Neurotrauma

Oxidative stress in Ca(2+)-induced membrane permeability transition in brain mitochondria

J Neurochem

Cytochrome c release and caspase activation in traumatic axonal injury

J Neurosci

Vulnerability of central neurons to secondary insults after in vitro mechanical stretch

Editor’s Choice: Review Article
Noninvasive Brain Stimulation to Modulate Neuroplasticity in Traumatic Brain Injury