Novel Neuromodulation Techniques to Assess Interhemispheric Communication in Neural Injury and Neurodegenerative Diseases

Abstract

Interhemispheric interaction has a major role in various neurobehavioral functions. Its disruption is a major contributor to the pathological changes in the setting of brain injury such as traumatic brain injury, peripheral nerve injury, and stroke, as well as neurodegenerative diseases. Because interhemispheric interaction has a crucial role in functional consequence in these neuropathological states, a review of noninvasive and state-of-the-art molecular based neuromodulation methods that focus on or have the potential to elucidate interhemispheric interaction have been performed. This yielded approximately 170 relevant articles on human subjects or animal models. There has been a recent surge of reports on noninvasive methods such as transcranial magnetic stimulation and transcranial direct current stimulation. Since these are noninvasive techniques with little to no side effects, their widespread use in clinical studies can be easily justified. The overview of novel neuromodulation methods and how they can be applied to study the role of interhemispheric communication in neural injury and neurodegenerative disease is provided. Additionally, the potential of each method in therapeutic use as well as investigating the pathophysiology of interhemispheric interaction in neurodegenerative diseases and brain injury is discussed. New technologies such as transcranial magnetic stimulation or transcranial direct current stimulation could have a great impact in understanding interhemispheric pathophysiology associated with acquired injury and neurodegenerative diseases, as well as designing improved rehabilitation therapies. Also, advances in molecular based neuromodulation techniques such as optogenetics and other chemical, thermal, and magnetic based methods provide new capabilities to stimulate or inhibit a specific brain location and a specific neuronal population.

Repetitive Transcranial Magnetic Stimulation with Resting-State Network Targeting for Treatment-Resistant Depression in Traumatic Brain Injury: A Randomized, Controlled, Double-Blinded Pilot Study

“…6 This is consistent with emerging evidence that rTMS modulates interhemispheric connectivity, which also is affected by TBI. 18 Further, animal models have successfully used rTMS to restore cortical excitability, 19 which is often compromised following TBI. 20 A prevailing concern limiting the study of rTMS in the setting of TBI is that these patients may be at higher risk of seizures, which is a rare side effect of rTMS 9 and a common complication of severe TBI.…”

Differences in high-definition transcranial direct current stimulation over the motor hotspot versus the premotor cortex on motor network excitability

“…Despite large variability in the baseline MSE measurements, HD-tDCS over premotor cortex, as hypothesized, led to significant and more reliable changes in MSE than HD-tDCS over the motor hotspot. Given that HD-tDCS over premotor cortex led to more reliable changes in cortical excitability, it is likely this was also captured in the MSE changes found in both hemispheres (i..e., an enhancement of the excitability in the stimulated hemisphere associated with a decrease of the excitability in the contralateral hemisphere 53,54 ). In line with previous studies 33 , MSE and functional connectivity seemed to be complementary metrics: MSE may be more sensitive and able to capture local changes in the motor network whereas traditional rs-fMRI functional connectivity would capture more robust changes between distant brain areas.…”

Non-invasive neuromodulation using rTMS and the Electromagnetic-Perceptive Gene (EPG) facilitates plasticity after nerve injury

“…Growing amounts of evidence from human and animal studies are establishing neuromodulation as an effective mechanism to strengthen and promote cortical functions 54 . The behavioral results indicate that both rTMS and EPG treatment have led to considerable improvement in sensorimotor functions.…”

“…For example, removing the afferents of the "good hand" via tourniquet-induced anesthesia, anesthetic block, and constraint induced therapy lead to improved hand function 15,16 . Harnessing the brain's innate plasticity mechanisms through non-invasive methods such as transcranial magnetic stimulation (TMS) has recently gained interest for use in functional and behavioral research as well as rehabilitation research after brain injury [17][18][19][20][21][22] and neurodegenerative diseases [23][24][25][26][27][28] . Various studies showed promising results using TMS in humans 17,25,29 , primates 30,31 , and rodents [32][33][34][35][36] .…”