Cortical stimulation for treatment of neurological disorders of hyperexcitability: a role of homeostatic plasticity

Hyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management of them is to suppress this hyperexcitability, such as having been exemplified by the use of certain antiepileptic drugs, their frequent refractoriness to drug treatment suggests likely different pathophysiological mechanism. Because the pathogenesis in these disorders exhibits a transition from an initial activity loss after injury or sensory deprivation to subsequent hyperexcitability and paroxysmal discharges, this process can be regarded as a process of functional compensation similar to homeostatic plasticity regulation, in which a set level of activity in neural network is maintained after injury-induced activity loss through enhanced network excitability. Enhancing brain activity, such as cortical stimulation that is found to be effective in relieving symptoms of these disorders, may reduce such hyperexcitability through homeostatic plasticity mechanism. Here we review current evidence of homeostatic plasticity in the mechanism of acquired epilepsy, neuropathic pain, and tinnitus and the effects and mechanism of cortical stimulation. Establishing a role of homeostatic plasticity in these disorders may provide a theoretical basis on their pathogenesis as well as guide the development and application of therapeutic approaches through electrically or pharmacologically stimulating brain activity for treating these disorders.

Electrocorticography with Direct Cortical Stimulation for a Left Temporal Glioma with Intractable Epilepsy

ELECTROCORTICOGRAPHY (ECoG), the intraoperative recording of cortical potentials, has played an important role in the surgical management of patients with medically intractable epilepsy. This technique is useful in epilepsy surgery to delineate margins of epileptogenic zones, guide resection,

A study on effective parameters of electric cortical stimulation for motor-sensory brain mapping

Objective The purpose of the study was to investigate the effective parameters of electric cortex stimulation (ECS) for functional brain mapping. Methods We collected 21 subjects who underwent epilepsy surgeries consecutively in Beijing Institute of Functional Neurosurgery with the epileptogenic zone located in perirolandic areas from

Electrical stimulation of cortical neurons promotes oligodendrocyte development and remyelination in the injured spinal cord

Background and early studies： Endogenous tri-potential neural stem cells （NSCs） exist in the adult mammalian central nervous system （CNS）. In the spinal cord, NSCs distribute throughout the entire cord, but exist predominately in white matter tracts. The phenotypic fate of these cells in white matter is glial, largely oligodendrocyte, but not neuronal.

High-frequency and brief-pulse stimulation pulses terminate cortical electrical stimulation-induced afterdischarges

Brief-pulse stimulation at 50 Hz has been shown to terminate afterdischarges observed in epilepsy patients. However, the optimal pulse stimulation parameters for terminating cortical electrical stimulation-induced afterdischarges remain unclear. In the present study, we examined the effects of different brief-pulse stimulation frequencies（5, 50 and 100 Hz） on cortical electrical stimulation-induced afterdischarges in 10 patients with refractory epilepsy. Results demonstrated that brief-pulse stimulation could terminate cortical electrical stimulation-induced afterdischarges in refractory epilepsy patients. In conclusion,（1） a brief-pulse stimulation was more effective when the afterdischarge did not extend to the surrounding brain area.（2） A higher brief-pulse stimulation frequency（especially 100 Hz） was more likely to terminate an afterdischarge.（3） A low current intensity of brief-pulse stimulation was more likely to terminate an afterdischarge.

Magnetic stimulation at Neiguan(PC6) acupoint increases connections between cerebral cortex regions

Stimulation at specific acupoints can activate cortical regions in human subjects.Previous studies have mainly focused on a single brain region.However,the brain is a network and many brain regions participate in the same task.The study of a single brain region alone cannot clearly explain any brain-related issues.Therefore,for the present study,magnetic stimulation was used to stimulate the Neiguan（PC6） acupoint,and 32-channel electroencephalography data were recorded before and after stimulation.Brain functional networks were constructed based on electroencephalography data to determine the relationship between magnetic stimulation at the PC6 acupoint and cortical excitability.Results indicated that magnetic stimulation at the PC6 acupoint increased connections between cerebral cortex regions.

Decoding brain responses to pixelized images in the primary visual cortex: implications for visual cortical prostheses

Visual cortical prostheses have the potential to restore partial vision. Still limited by the low-resolution visual percepts provided by visual cortical prostheses, implant wearers can currently only ＂see＂ pixelized images, and how to obtain the specific brain responses to different pixelized images in the primary visual cortex（the implant area） is still unknown. We conducted a functional magnetic resonance imaging experiment on normal human participants to investigate the brain activation patterns in response to 18 different pixelized images. There were 100 voxels in the brain activation pattern that were selected from the primary visual cortex, and voxel size was 4 mm × 4 mm × 4 mm. Multi-voxel pattern analysis was used to test if these 18 different brain activation patterns were specific. We chose a Linear Support Vector Machine（LSVM） as the classifier in this study. The results showed that the classification accuracies of different brain activation patterns were significantly above chance level, which suggests that the classifier can successfully distinguish the brain activation patterns. Our results suggest that the specific brain activation patterns to different pixelized images can be obtained in the primary visual cortex using a 4 mm × 4 mm × 4 mm voxel size and a 100-voxel pattern.

Novel role for transcranial magnetic stimulation to study post-traumatic respiratory neuroplasticity

Transcranial magnetic stimulation-a tool used in humans：Transcranial magnetic stimulation（TMS）is a non-invasive widespread clinical tool used to stimulate cortical areas in human subjects.This technique utilizes a brief,highly intense magnetic field applied to cortical areas,which locally depolarized interneurons（Weber and Eisen,2002）.

Role of functional imaging in the development and refinement of invasive neuromodulation for psychiatric disorders

Deep brain stimulation(DBS) is emerging as a pow-erful tool for the alleviation of targeted symptoms in treatment-resistant neuropsychiatric disorders. Despite the expanding use of neuropsychiatric DBS, the mecha-nisms responsible for its effects are only starting to be elucidated. Several modalities such as quantitative elec-troencephalography as well a intraoperative recordings have been utilized to attempt to understand the under-pinnings of this new treatment modality, but functional imaging appears to offer several unique advantages. Functional imaging techniques like positron emission tomography, single photon emission computed tomog-raphy and functional magnetic resonance imaging have been used to examine the effects of focal DBS on activ-ity in a distributed neural network. These investigations are critical for advancing the field of invasive neuro-modulation in a safe and effective manner, particularly in terms of defining the neuroanatomical targets and refining the stimulation protocols. The purpose of this review is to summarize the current functional neuroim-aging findings from neuropsychiatric DBS implantation for three disorders: treatment-resistant depression, obsessive-compulsive disorder, and Tourette syndrome. All of the major targets will be discussed(Nucleus ac-cumbens, anterior limb of internal capsule, subcallosal cingulate, Subthalamic nucleus, Centromedial nucleus of the thalamus-Parafasicular complex, frontal pole, and dorsolateral prefrontal cortex). We will also address some apparent inconsistencies within this literature, and suggest potential future directions for this promis-ing area.

Differences between physiological and pathological convulsive thresholds in patients with epilepsy

BACKGROUND： Physiological convulsive thresholds degrade when the brain is in some pathologic states; thus, a level of stimulus that cannot provoke a convulsion may evoke a seizure or epileptic seizure. OBJECTIVE： To investigate the changes that occur in the brain when the physiological convulsive threshold becomes pathological, and to determine what differences occur in pathological and physiological convulsive thresholds during the development of epilepsy. DESIGN： A randomized controlled animal experiment. SETTING： Research Institute of Epilepsy of Shanxi Medical University; Department of Neurology, The Third Hospital of Shanxi Medical University; Research Institute of Function of Shanxi Medical University. MATERIALS： Thirty-six female Wistar rats were selected for this study. The rats were obtained from the experimental animal center of Shanxi Medical University. All laboratory procedures complied with animal ethical standards. The animals were randomly divided into three groups： a strong current group, a weak current group and a control group, with 12 rats in each group. An automatic determinator of seizure threshold was made at Shanxi Medical University and Taiyuan University of Technology. Two bipolar stainless steel stimulating electrodes and an electrode connector （diameter 1.2 ram） were made at Taiyuan University of Technology. METHODS： This study was performed in the laboratory of Research Institute of the Epilepsy of Shanxi Medical University between December 2005 and August 2006. The threshold of localized seizures was measured by performing direct cortical stimulation in rats under anesthesia. After 1 week of post-operative recovery, electric stimulation was started with three different kinds of stimulation. Seizure activity was induced by a ramp-shaped single train of biphasic pulses （50 Hz, total pulse duration of 2 ms, increasing from 0 to 2 000μ A in 15 seconds）. The threshold of localized seizures （TLS） has been defined as the minimum current intensity necessary to provoke convulsion of the forelimbs and/or facial muscles. Up to the TLS, if stimulation continued, the current intensity necessary to provoke the generalized seizures is called the threshold of generalized seizures （TGS）. If stimulation is continued for about 2 seconds when the TGS is reached, rats still showed generalized clonic activity after stimulation ceased. When seizures stopped, a short period of immobility can be observed. The current intensity is called the threshold of prolonged seizures （TPS）. The rats in the strong current group were stimulated up to the current level required to reach the TPS. In the course of stimulation, first, the TLS was recorded, then the TGS, and finally the TPS. The stimulation interval in one session was 10 minutes, repeated twice daily. The rats in the weak current group were only stimulated up to the current levels required to reach the TGS; first, the TLS was recorded and then the TGS was measured at the same time as the strong current group. Control animals were also equipped with a full electrode set and placed in the same conditions, but no stimulation took place, only electroencephalogram （EEG） recording at the same times as the experimental groups. MAIN OUTCOME MEASURES： ① Stimulation of the two experimental groups lasted for 11 weeks and then observation of their behavior and electroencephalogram recording continued for 4 weeks. The control group was also observed over a total of 15 weeks. ② Observing neuronal damage/loss in the hippocampus with a light microscope using a 250x visual field. RESULTS： All 36 Wistar rats were included in the final analysis. At the beginning of the experiment, the convulsive thresholds were all above 1 100 μA, although there were significant individual variations among rats of the same group. Those thresholds quickly declined during the initial 4 weeks of repetitive electrical stimulation. The convulsive thresholds approached a constant level in the 10^th week after commencement of stimulation. There were no significant changes in thresholds when stimulations lasted longer; the convulsive thresholds and the variations in rats of the same group were significantly lower than at the beginning of the trial （P 〈 0.01）. An interictal discharge was also recorded in the 3^rd week in the strong current group, and in the 8th week in the weak current group; these discharges were concomitant with neuronal damage and loss in the hippocampus. There was no abnormality observed in the control group. CONCLUSION： These findings indicated that the convulsion threshold in the brain should be divided into two stages： a physiological convulsive threshold and a pathological convulsive threshold （epileptic threshold） The epileptic threshold is created by pathologically acquired factors, which give rise to brain damage. The increase in the intensity of these pathologically acquired factors led to aggravation of damage.

A useful electroencephalography(EEG) marker of brain plasticity: delta waves

Plasticity is a natural property of living organisms that is crucial for adaptation and evolution.Over the last decades,the availability of sophisticated neuroimaging techniques（in particular,functional magnetic resonance imaging（f MRI）,and transcranial magnetic stimulation（TMS））,has made it possible to explore in vivo the on-line functioning of brain and its plasticity.However,

Novel rehabilitation paradigm for restoration of hand functions after tetraplegia

The letter by Bouton et al.（2016）“Restoring cortical control of functional movement in a human with quadriplegia”presents a case report of a 24 year old male with tetraplegia（C5–6）.The goal of the work was to bypass the spinal cord injury（SCI）lesion to stimulate the right forearm muscles to perform six movements and daily functional tasks.

Preoperative 3T high field blood oxygen level dependent functional magnetic resonance imaging for glioma involving sensory cortical areas

Background Localization of sensory cortical areas during the operation is essential to preserve the sensory function. Intraoperative direct electrostimulation under awake anesthesia is the golden standard but time-consuming. We applied 3T high field blood oxygen level-dependent （BOLD） functional magnetic resonance imaging （fMRI） to identify the relationship between glioma and cortical sensory areas preoperatively and to guide intraoperative direct electrostimulation for quick and precise localization. Methods Five glioma patients with sensory cortex involvement by or next to the lesion had preoperative BOLD fMRI to determine the spatial relationship of cortical sensory areas to the tumours. Bilateral hand opposite movement was performed by these patients for fMRI. Precentral and postcentral gyri were identified by electrical stimulation during the operation. Karnofsky Performance Status scores of the patients＇ pre- and postoperative and the role of BOLD fMRI were evaluated. Results The cortical sensory areas were all activated in five glioma patients involving postcentral gyrus areas by BOLD fMRI with bilateral hand opposite movement. The detected activation areas corresponded with the results from cortical electrical stimulation. Conclusions The relationship between cortical sensory areas and tumour can be accurately shown by BOLD fMRI before operation. And the information used to make the tumour resection could obtain good clinical results.

Plasticity of motor function and surgical outcomes in patients with cerebral arteriovenous malformation involving primary motor area:insight from fMRI and DTI

Background:Patients who have a cerebral arteriovenous malformation (cAVMs) in the motor cortex can have displaced function. The finding and its relationship to recovery from surgery is not known. Methods:We present the five cases with cAVMs involving precentral knob and/or paracentral lobule and without preoperative motor deficits. We used motor activation areas derived from Functional functional MRI (fMRI) as a region of interesting (ROI) to launch the plasticity of cerebrospinal tracts (CST). All the results were incorporated into the neuronavigation platform for surgical treatment. Intraoperative electric cortical stimulation (ECS) was used to map motor areas. Modified Rankin Scale (mRS) of hands and feets were performed on postoperative day 2, 7 and at month 3, 6 during follow-up period. All the patients suffered from motor deficits regardless of cortical activation patterns. Results:Three patients showed functionally seeded CST in or around the AVM, and were validated by intraoperative electrical stimulation (ECS). Patient 4 had two aberrant functionally seeded fiber tracts away from the lesion, but were proved to be non-functional by postoperative motor deficits. Patient 3 with motor cortex and fiber tract within a diffuse AVMs nidus, complete paralysis of upper extremity after operation and has a persistent motor deficit during 6-month follow-up period. Conclusions:The plasticity of motor cortex on fMRI doesn’t prevent post-operative motor deficits. Functionally mapped fiber tract within or abutting AVM nidus predicts transient and persistent motor deficit.