A narrative review on invasive brain stimulation for treatment-resistant depression

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Intraoperative Motor Evoked Potential Improvement in Cervical Spondylotic Myelopathy: Comparison of Cortical Stimulation Parameters

Effects of Electric Cortical Stimulation (ECS) and Transcranial Direct Current Stimulation (tDCS) on Rats With a Traumatic Brain Injury

OBJECTIVE: To evaluate the effects of electric cortical stimulation (ECS) and transcranial direct current stimulation (tDCS) on motor and cognitive function recovery and brain plasticity in focal traumatic brain injury (TBI) of rats model. METHODS: Forty rats were pre-trained to perform a single pellet reaching task (SPRT), rotarod test (RRT), and Y-maze test for 14 days, then a focal TBI was induced by a weight drop model on the motor cortex. All rats were randomly assigned to one of the three groups: anodal ECS (50 Hz and 194 μs) (ECS group), tDCS (0.1 mA, 50 Hz and 200 μs) (tDCS group), and no stimulation as a control group. Four-week stimulation, including rehabilitation, was started 3 days after the operation. SPRT, RRT, and Y-maze were measured from day 1 to day 28 after the TBI was induced. Histopathological and immunohistochemistry staining evaluations were performed at 4 weeks. RESULTS: SPRT was improved from day 7 to day 26 in ECS, and from day 8 to day 26 in tDCS compared to the control group (p < 0.05). SPRT of ECS group was significantly improved on days 3, 8, 9, and 17 compared to the tDCS group. Y-maze was improved from day 8 to day 16 in ECS, and on days 6, 12, and 16 in the tDCS group compared to the control group (p < 0.05). Y-maze of the ECS group was significantly improved on day 9 to day 15 compared to the tDCS group. The c-Fos protein expression was better in the ECS group and the tDCS group compared to the control group. CONCLUSION: Electric stimulation in rats modified with a focal TBI is effective for motor recovery and brain plasticity. ECS induced faster behavioral and cognitive improvements compared to tDCS during the recovery period of rats with a focal TBI.

Limitation of Intraoperative Transcranial Electrical Stimulation-Motor Evoked Potential Monitoring During Brain Tumor Resection Adjacent to the Primary Motor Cortex

Transcranial electrical stimulation-motor evoked potential (TES-MEP) is a valuable intraoperative monitoring technique during brain tumor surgery. However, TES can stimulate deep subcortical areas located far from the motor cortex. There is a concern about false-negative results from the use of TES-MEP during resection of those tumors adjacent to the primary motor cortex. Our study reports three cases of TES-MEP monitoring with false-negative results due to deep axonal stimulation during brain tumor resection. Although no significant change in TES-MEP was observed during surgery, study subjects experienced muscle weakness after surgery. Deep axonal stimulation of TES could give false-negative results. Therefore, a combined method of TES-MEP and direct cortical stimulation-motor evoked potential (DCS-MEP) or direct subcortical stimulation should be considered to overcome the limitation of TES-MEP.

Mapeo del lenguaje utilizando estimulación magnética transcraneal repetitiva por navegación: un estudio comparativo con la estimulación cortical directa intraoperatoria / Language mapping using repetitive transcranial magnetic stimulation by navigation: a comparative study with direct intraoperative cortical stimulation

Introducción: la estimulación cortical directa (DCS) es una metodología corrientemente usada para localizar áreas del lenguaje en intervenciones quirúrgicas que incluyan resecciones.La estimulación magnética transcraneana repetitiva (rTMS) a demostrado también su capacidad para inducir alteraciones transitorias. Recientemente el desarrollo del Sistema de Navegación de TMS asegura precisa localización del sitio estimulado. El objetivo del trabajo es estudiar la confiabilidad de la estimulación magnética transcraneal repetitiva navegada (nrTMS) en la localización de los sitios del lenguaje. Métodos: Once pacientes seleccionados para mapeo del lenguaje por DCS fueron evaluados pre-cirugía con nrTMS. Los mapeos de lenguaje prequirúrgicos mediante nrTMS fueron comparados con DCS. Resultados: Un total de 25 nrTMS sitios del lenguaje y 38 DCS fueron localizados. La sensibilidad y la especificidad obtenida fue de 88.4 y 95.6, respectivamente. La distancia media fue evaluada en 4,5mm. Conclusiones: Los dispositivos de nrTMS permiten la identificación de las áreas corticales del lenguaje. Con un alto grado de concordancia con el mapeo TMS. La nrTMS se muestra como una herramienta de interés en la investigación y aplicación práctica en la función del lenguaje.

Introduction: direct cortical stimulation (DCS) is currently used to localise language areas in surgical resections. Repetitive transcranial magnetic stimulation (rTMS) has also shown its capacity to induce transient language alterations. Newly developed Navigated Brain Systems of TMS ensure precise topographical localisation of the stimulated site. The objective was to study the reliability of navigated repetitive transcranial magnetic stimulation (nrTMS) in language sites localisation.Methods: Eleven patients selected for DCS language mapping were presurgically evaluated with nrTMS. These presurgicalnrTMS language maps were then compared with DCS.Results: A total number of 25 nrTMS and 38 DCS language sites were localised. Sensitivity and specificity were calculated as 88.4 and 95.6 respectively. Mean distance was assessed as 4.5 millimetres. Conclusions: nrTMS devices allow identification of cortical language areas, with a high degree of concordance to TMS mapping. NrTMS shows up as an interesting tool for research and practical application in language function.

Role of the Cerebral Cortex on Vestibular Compensation Following Unilateral Labyrinthectomy in Rats / 대한평형의학회지

OBJECTIVE: The cerebral cortex can modulate vestibular functions through direct control of neuronal activities in the vestibular nuclei. The purpose of this study was to investigate the effect of unilateral cortical lesion or cortical stimulation on static vestibular symptoms and vestibular nuclear activities at the acute stage of vestibular compensation following unilateral labyrinthectomy (UL) in rats. METHODS: The photothrombic ischemic injury using rose bengal was induced in the primary motor cortex or primary sensory cortex, and electrical stimulation was applied to the primary motor cortex, primary sensory cortex, or sencondary sensory cortex, respectively, in unilateral labyrinthectomized rats. Static vestibular symptoms including ocular movement and postural deficits, and expression of c-Fos protein in the medial vestibular nucleus (MVN) were measured. RESULTS: Lesion of the motor cortex produced a marked postural deficit with paralytic weakness in the hindlimb contralateral to UL. Number of spontaneous nystagmus in animals receiving cortical lesion was significantly increased 2, 6, and 12 hours after UL compared with animals being UL only. Lesion of the primary motor cortex or stimulation of the S2 sensory cortex decreased expression of c-Fos protein in MVN following UL compared with UL only group. Electrical stimulation of S2 sensory areas caused significant reduction of static vestibular symptoms and decreased expression of c-Fos protein in MVN 24 hours following UL. CONCLUSION: The present results suggest that cerebral cortex involves in recovery of static vestibular symptoms during vestibular compensation following UL.

The Effect of Electric Cortical Stimulation after Focal Traumatic Brain Injury in Rats

OBJECTIVE: To evaluate the effects of electric cortical stimulation in the experimentally induced focal traumatic brain injury (TBI) rat model on motor recovery and plasticity of the injured brain. METHOD: Twenty male Sprague-Dawley rats were pre-trained on a single pellet reaching task (SPRT) and on a Rotarod task (RRT) for 14 days. Then, the TBI model was induced by a weight drop device (40 g in weight, 25 cm in height) on the dominant motor cortex, and the electrode was implanted over the perilesional cortical surface. All rats were divided into two groups as follows: Electrical stimulation (ES) group with anodal continuous stimulation (50 Hz and 194 micros duration) or Sham-operated control (SOC) group with no electrical stimulation. The rats were trained SPRT and RRT for 14 days for rehabilitation and measured Garcia's neurologic examination. Histopathological and immunostaining evaluations were performed after the experiment. RESULTS: There were no differences in the slice number in the histological analysis. Garcia's neurologic scores & SPRT were significantly increased in the ES group (p<0.05), yet, there was no difference in RRT in both groups. The ES group showed more expression of c-Fos around the brain injured area than the SOC group. CONCLUSION: Electric cortical stimulation with rehabilitation is considered to be one of the trial methods for motor recovery in TBI. However, more studies should be conducted for the TBI model in order to establish better stimulation methods.

Aprendizagem hábil-motora baseada em estratégias de observação e uso da estimulação cortical via sintetização fótica e auditiva / Skilled-motor learning based on observation strategies and the use of cortical stimulation via visual and aural synthesis

O objetivo deste estudo foi a verificação da possibilidade teórica de que a aprendizagem de uma habilidade motora decorra da observação do aprendiz sobre outros praticantes e seja intensificada em função de um protocolo de sintetização de ondas corticais via estimulação cortical. A amostra foi constituída por 15 crianças, de ambos os gêneros, com faixa etária entre 4-5 anos, que foram submetidas a treinamento motor conforme teoria dos neurônios-espelho. Foi realizado eletroencefalograma, em dois momentos da pesquisa (pré e pós-testes) e observada a performance motora dos grupos. Observou-se que, na Fase de Aquisição e Transferência, os grupos obtiveram melhora na performance motora pela diminuição na média de erros absolutos e equilíbrio nas ondas corticais, embora não tenha sido significativa. O estudo da hipótese investigada na abordagem dos neurônios-espelho associada à estimulação cortical demonstrou melhora no desempenho, na agilidade e na capacidade hábil-motriz.

To verify the theoretical possibility that learning a motor skill may come from the observation of other practitioners and be intensified due to the protocol of synthesis of cortical waves via cortical stimulation was the objective of this study. Fifteen children, both male and female, aged 4-to-5 years old, divided randomly into three groups which were submitted to a motor training according to the mirror-neuron theory. Electroencephalogram was carried out pre and post-training in order to verify the possible alterations in the cortical standard, and the motor performance of the groups was observed. It was observed that in the Acquisition and Transference Phase, the group obtained improvement in the motor performance due to the decrease of absolute mistakes average and balance in the cortical waves. The values obtained were not significant. The hypothesis of mirror-neuron approach associated with cortical stimulation demonstrated increased global performance of the group, improving the development, the agility and the skilled-motor capacity.

Research on cortical stimulation for treatment of stroke / 上海交通大学学报（医学版）

Stroke is characterized by a group of acute cerebral vascular diseases which attack acutely with focal neurological deficits. Residual motor deficits often sojourn after stroke. Cortical stimulation, which is a technique developed many decades ago, has recently re-emerged as a promising method for researchers in their quest to causally probe cortical representations of sensorimotor and cognitive functions and to facilitate the treatment of various neuropsychiatric disorders. The article summarizes the research progress of cortical stimulation in the promotion of motor function recovery after stroke, the method of operation, the possible mechanisms and the prospect.

The Comparison of the Anesthetic Regimens for Functional Direct Cortical Stimulation Mapping during Craniotomy / 대한마취과학회지

BACKGROUND: Recently, functional direct cortical stimulation mapping is frequently used during craniotomy for the surgery of brain pathology (tumors, epileptic foci etc.) within or close to the central motor area. We reviewed and analyzed our experiences to evaluate the safety and efficacy of our hospital's anesthetic management regimens. METHODS: We used three anesthetic regimens (isoflurane fentanyl; propofol fentanyl; awake craniotomy, conscious sedation analgesia) in 44 patients. We evaluated the success ratio of mapping and the incidence of intraoperative problems (seizures, changes in vital signs etc) in each regimens. RESULTS: In awake craniotomy group, functional mapping is performed successfully in all patients but there were some intraoperative problems (hypertension; 3 in 11 patients, hypercapnia; 3 in 11 patients, change to general anesthesia required; 1 in 12 patients). In general anesthesia groups, there were no significant differences between isoflurane treated patients and propofol treated patients in the success ratio of mapping (17/20 vs 11/12) and the incidence of intraoperative problems (seizure; 3/20 vs 1/12, hypertension; 2/20 vs 1/12). CONCLUSION: This results suggest that the anesthetic management regimens used in our hospital provide suitable conditions for craniotomies when brain mapping is required.

Modulations of soleus H-reflex induced by acoustic stimulations in man / 体力科学

The present study was undertaken to examine the effects of acoustic stimulation on human spinal motoneuron excitability. For this purpose, we used the soleus (Sol) H-reflex as a test reflex, and three different types of acoustic stimuli as conditioning stimuli. The features of the acoustic stimuli were as follows, 1) click sound (CS), 2) tone burst composed of 11 click sounds (TBL, interstimulus interval 10 ms), 3) tone burst composed of 21 click sounds (TBH, interstimulus interval 5 ms) . The intensity and frequency of each sound was 110 dB and 0.5 kHz, respectively.<BR>Significant facilitation of the Sol H-reflex occurred at conditioning-testing (C-T) intervals of 50 ms in all subjects when the TBL stimulus was used (mean±S.D.; 50.3±8.2 ms) . This facilitatory effect appeared early and later when TBH (43.7±3.7 ms) and CS (59.2±4.5 ms) stimuli were used, respectively. The maximum facilitatory effect appeared at a C-T interval of 100 ms (mean and S. E.; 98.0±0.8 ms) and the amount of peak facilitation at that time was 156.1±1.4% (relative to the control value) . Thereafter, the amount of facilitation decreased sharply up to a C-T interval of 200 ms. However, slight but significant facilitation was observed continuously up to a C-T interval of 500 ms. No significant inhibition of the Sol H-reflex was observed between a C-T interval of 0 and 500 ms in all subjects.<BR>Irrespective of whether the magnetic cortical stimulation was given before or after the Sol H-reflex at a short interval (-2 to 2 ms), the acoustic facilitation of the Sol H-reflex was not changed with a C-T interval of 50 ms. Additional facilitation due to magnetic cortical stimulation was, however, obtained in one of the four subjetcts when a C-T interval of 100 ms was used.<BR>These results suggest that the acoustic facilitation of the Sol H-reflex is composed of three different facilitatory mechanisms; 1) a pathway with a high threshold and shorter latency (about 40 ms), 2) a pathway with a lower threshold and medium latency (about 60 ms), and 3) a pathway with a relativelyhigh threshold and longer latency (longer than 200 ms) . In addition, we discussed the mechanisms that underlie the facilitatory effects of the Sol H-reflex.