Transcranial magnetic stimulation facilitates neurorehabilitation after pediatric traumatic brain injury

Abstract

Traumatic brain injury (TBI) is the leading cause of death and disability among children in the United States. Affected children will often suffer from emotional, cognitive and neurological impairments throughout life. In the controlled cortical impact (CCI) animal model of pediatric TBI (postnatal day 16–17) it was demonstrated that injury results in abnormal neuronal hypoactivity in the non-injured primary somatosensory cortex (S1). It materializes that reshaping the abnormal post-injury neuronal activity may provide a suitable strategy to augment rehabilitation. We tested whether high-frequency, non-invasive transcranial magnetic stimulation (TMS) delivered twice a week over a four-week period can rescue the neuronal activity and improve the long-term functional neurophysiological and behavioral outcome in the pediatric CCI model. The results show that TBI rats subjected to TMS therapy showed significant increases in the evoked-fMRI cortical responses (189%), evoked synaptic activity (46%), evoked neuronal firing (200%) and increases expression of cellular markers of neuroplasticity in the non-injured S1 compared to TBI rats that did not receive therapy. Notably, these rats showed less hyperactivity in behavioral tests. These results implicate TMS as a promising approach for reversing the adverse neuronal mechanisms activated post-TBI. Importantly, this intervention could readily be translated to human studies.

Immediate Effects of Repetitive Magnetic Stimulation on Single Cortical Pyramidal Neurons

“…Transcranial Magnetic Stimulation (TMS) is a non-invasive method of neural activation, currently used as a therapeutic intervention in neurological disorders like depression [1, 2], and migraine [3]; and being investigated for clinical applications in epilepsy [4, 5], movement disorders [6], stroke [7, 8], brain injury [9], and schizophrenia [10, 11]. It is also frequently used as an investigative tool for basic neuroscience [12–17].…”

New Vision for Visual Prostheses

“…Electromagnetic induction generates currents that are capable of stimulating neurons within the specific region. Since non-invasive stimulation of the brain reduces the risks encountered in surgical patients, such as hemorrhage, infection, and the overall cost of the procedure, TMS has recently gained interest for use in functional and behavioral research as well as rehabilitation research after brain injury (Ferbert et al, 1992;Celnik et al, 2009;Lu et al, 2015;Shin et al, 2018;Krishnan et al, 2019).…”

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

“…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] .…”

“…Importantly, TMS has shown effectiveness in manipulating transcallosal communication in patients suffering from peripheral injury 37,38 and alleviating pain associated with injury 39 . TMS has also been shown to increase neuronal excitability and markers associated with plasticity such as brain-derived neurotrophic factor (BDNF) [40][41][42] , c-fos 40 and Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) 35 . However, it is still not clear when is the optimal and most effective time for TMS intervention (acute, subacute or chronic phase) to take place after injury.…”