Brain structure comparison among Parkinson disease, essential tremor, and healthy controls using 7T MRI.

Both Parkinson disease (PD) and Essential tremor (ET) are movement disorders causing tremors in elderly individuals. Although PD and ET are different disease, they often present with similar initial symptoms, making their differentiation challenging with magnetic resonance imaging (MRI) techniques. This study aimed to identify structural brain differences among PD, ET, and health controls (HCs) using 7-Tesla (T) MRI. We assessed the whole-brain parcellation in gray matter volume, thickness, subcortical volume, and small regions of basal ganglia in PD (n = 18), ET (n = 15), and HCs (n = 18), who were matched for age and sex. Brain structure analysis was performed automatic segmentation through Freesurfer software. Small regions of basal ganglia were manually segmented by ITK-SNAP. Additionally, we examined the associations between clinical indicators (symptom duration, unified Parkinson diseases rating scale (UPDRS), and clinical rating scale for tremor (CRST)) and brain structure. PD showed a significant reduction in gray matter volume in the postcentral region compared to ET. ET showed a significant reduction in cerebellum volume compared to HCs. There was a negative correlation between CRST scores (B and C) and gray matter thickness in right superior frontal in ET. This study demonstrated potential of 7T MRI in differentiating brain structure differences among PD, ET, and HCs. Specific findings, such as parietal lobe atrophy in PD compared to ET and cerebellum atrophy in ET compared to HCs, the importance of advanced imaging techniques in accurately diagnosing and distinguishing between movement disorders that present with similar initial symptoms.

Can we predict overall survival using machine learning algorithms at 3-months for brain metastases from non-small cell lung cancer after gamma knife radiosurgery?

Gamma knife radiosurgery (GRKS) is widely used for patients with brain metastases; however, predictions of overall survival (OS) within 3-months post-GKRS remain imprecise. Specifically, more than 10% of non-small cell lung cancer (NSCLC) patients died within 8 weeks of post-GKRS, indicating potential overtreatment. This study aims to predict OS within 3-months post-GKRS using machine learning algorithms, and to identify prognostic features in NSCLC patients. We selected 120 NSCLC patients who underwent GKRS at Chungbuk National University Hospital. They were randomly assigned to training group (n = 80) and testing group (n = 40) with 14 features considered. We used 3 machine learning (ML) algorithms (Decision tree, Random forest, and Boosted tree classifier) to predict OS within 3-months for NSCLC patients. And we extracted important features and permutation features. Data validation was verified by physician and medical physicist. The accuracy of the ML algorithms for predicting OS within 3-months was 77.5% for the decision tree, 72.5% for the random forest, and 70% for the boosted tree classifier. The important features commonly showed age, receiving chemotherapy, and pretreatment each algorithm. Additionally, the permutation features commonly showed tumor volume (>10 cc) and age as critical factors each algorithm. The decision tree algorithm exhibited the highest accuracy. Analysis of the decision tree visualized data revealed that patients aged (>71 years) with tumor volume (>10 cc) were increased risk of mortality within 3-months. The findings suggest that ML algorithms can effectively predict OS within 3-months and identify crucial features in NSCLC patients. For NSCLC patients with poor prognoses, old age, and large tumor volumes, GKRS may not be a desirable treatment.

Validation of real-time inside-out tracking and depth realization technologies for augmented reality-based neuronavigation.

PURPOSE: Concomitant with the significant advances in computing technology, the utilization of augmented reality-based navigation in clinical applications is being actively researched. In this light, we developed novel object tracking and depth realization technologies to apply augmented reality-based neuronavigation to brain surgery. METHODS: We developed real-time inside-out tracking based on visual inertial odometry and a visual inertial simultaneous localization and mapping algorithm. The cube quick response marker and depth data obtained from light detection and ranging sensors are used for continuous tracking. For depth realization, order-independent transparency, clipping, and annotation and measurement functions were developed. In this study, the augmented reality model of a brain tumor patient was applied to its life-size three-dimensional (3D) printed model. RESULTS: Using real-time inside-out tracking, we confirmed that the augmented reality model remained consistent with the 3D printed patient model without flutter, regardless of the movement of the visualization device. The coordination accuracy during real-time inside-out tracking was also validated. The average movement error of the X and Y axes was 0.34 ± 0.21 and 0.04 ± 0.08 mm, respectively. Further, the application of order-independent transparency with multilayer alpha blending and filtered alpha compositing improved the perception of overlapping internal brain structures. Clipping, and annotation and measurement functions were also developed to aid depth perception and worked perfectly during real-time coordination. We named this system METAMEDIP navigation. CONCLUSIONS: The results validate the efficacy of the real-time inside-out tracking and depth realization technology. With these novel technologies developed for continuous tracking and depth perception in augmented reality environments, we are able to overcome the critical obstacles in the development of clinically applicable augmented reality neuronavigation.

Optimal mask fixation method for frameless radiosurgery with Leksell Gamma Knife IconTM.

The Leksell Gamma Knife (LGK) IconTM is used for mask-based and frame-based fixation. The mask fixation provides a noninvasive method. However, an optimal mask fixation method is yet to be established. We evaluated the characteristics of three mask fixation methods (Plain, Folded, and Wide) for the LGK IconTM . Force-sensitive resistor sensors were attached to the forehead, supraorbital, zygoma, mandible, and occipital bone of the phantom, and digital humidity and temperature sensors were attached to both temporal lobes. Cone-beam computed tomography (CBCT) and high-definition motion management (HDMM) for each mask fixation method were used to evaluate the phantom motion during the initial application. Subsequently, the mask was removed and reapplied on the second (1st reapplication) and third days (2nd reapplication). In the initial application, forces acting on most portions of the phantom were stabilized within 1.5 h. The largest force acted on the occipital bone for the Plain and Wide methods and on the mandible for the Folded method. The temperature rapidly approaches the initial temperature, whereas the humidity gradually approached the initial humidity in all fixation methods. The Folded method exhibited a significantly lower translation along the Y-axis of the Leksell coordinate system, and rotations along all axes were under 0.5°. The HDMM values remained at 0.1 mm for all fixation methods. In the reapplications, the force acting on the occipital bone was significantly greater than that during the initial application for all mask fixation methods; the temperature and humidity remained unchanged. All mask fixation methods in the 1st reapplication were not significantly different from those in the 2nd reapplication. The Folded method is recommended as an optimal mask fixation for patients who require tight fixation; the Wide method can be considered if patient comfort is a priority.

Avoiding a Collision in Gamma Knife Radiosurgery : A Modified Mask Fixation Method.

OBJECTIVE: The latest version of the Leksell Gamma Knife IconTM allows for mask- and frame-based fixation. Although mask fixation provides fractionated treatment and immobilization using a noninvasive method, it is not free from collision. The authors investigated the collision problem with a modified mask fixation method. METHODS: This study presents a case of two meningiomas in the frontal area, where a collision occurs in the occipital area. A modified mask fixation method was introduced to avoid the collision : first, the edges of the head cushion were cut off and polystyrene beads with a diameter of approximately 5 cm were removed. Next, the head cushion was sealed using a stapler. Finally, the head cushion was flattened in the adapter. We compared the shot coordinates, 3-dimensional (3D) error, clearance distance, and vertical depth of the head cushion between the initial and modified mask fixations. RESULTS: When comparing the initial and modified mask fixations, the difference in the shot coordinates was +10.5 mm along the y-axis, the difference in the 3D error was approximately 18 mm, and the difference in clearance was -10.2 mm. The head cushion was approximately 8 mm deeper in the modified mask fixation. CONCLUSION: Based on these findings, we recommend a modified mask fixation method for gamma knife radiosurgery using ICON with a collision.

Volume prediction for large brain metastases after hypofractionated gamma knife radiosurgery through artificial neural network.

The effectiveness of single-session gamma knife radiosurgery (GKRS) for small metastatic brain tumors has been proven, but hypofractionated GKRS (hfGKRS) for large brain metastases (BM) from the linear quadratic (LQ) model is uncertain. The purpose of this study was to investigate volume changes large BM after hfGKRS from the LQ model and predict volume changes using artificial neural network (ANN). We retrospectively investigated the clinical findings of 28 patients who underwent hfGKRS with large BM (diameter >3 cm or volume >10 cc). A total of 44 tumors were extracted from 28 patients with features. We randomly divided 30 large brain tumors as training set and 14 large brain tumors as test set. To predict the volume changes after hfGKRS, we used ANN models (single-layer perceptron (SLP) and multi-layer perceptron (MLP)). The volume reduction was 96% after hfGKRS for large BM from the LQ model. ANN model predicted volume changes with 70% and 80% accuracy for SLP and MLP, respectively. Even in large BM, hfGKRS from the LQ model could be a good treatment option. Additionally, the MLP model could predict volume changes with 80% accuracy after hfGKRS for large BM.

Navigation of frameless fixation for gamma knife radiosurgery using fixed augmented reality.

Augmented reality (AR) offers a new medical treatment approach. We aimed to evaluate frameless (mask) fixation navigation using a 3D-printed patient model with fixed-AR technology for gamma knife radiosurgery (GKRS). Fixed-AR navigation was developed using the inside-out method with visual inertial odometry algorithms, and the flexible Quick Response marker was created for object-feature recognition. Virtual 3D-patient models for AR-rendering were created via 3D-scanning utilizing TrueDepth and cone-beam computed tomography (CBCT) to generate a new GammaKnife Icon™ model. A 3D-printed patient model included fiducial markers, and virtual 3D-patient models were used to validate registration accuracy. Registration accuracy between initial frameless fixation and re-fixation navigated fixed-AR was validated through visualization and quantitative method. The quantitative method was validated through set-up errors, fiducial marker coordinates, and high-definition motion management (HDMM) values. A 3D-printed model and virtual models were correctly overlapped under frameless fixation. Virtual models from both 3D-scanning and CBCT were enough to tolerate the navigated frameless re-fixation. Although the CBCT virtual model consistently delivered more accurate results, 3D-scanning was sufficient. Frameless re-fixation accuracy navigated in virtual models had mean set-up errors within 1 mm and 1.5° in all axes. Mean fiducial marker differences from coordinates in virtual models were within 2.5 mm in all axes, and mean 3D errors were within 3 mm. Mean HDMM difference values in virtual models were within 1.5 mm of initial HDMM values. The variability from navigation fixed-AR is enough to consider repositioning frameless fixation without CBCT scanning for treating patients fractionated with large multiple metastases lesions (> 3 cm) who have difficulty enduring long beam-on time. This system could be applied to novel GKRS navigation for frameless fixation with reduced preparation time.

Optogenetic Stimulation of the Anterior Cingulate Cortex Modulates the Pain Processing in Neuropathic Pain: A Review.

Neuropathic pain is characterized by hypersensitivity, hyperalgesia, and allodynia, which is caused by damage to the somatosensory nervous system. It substantially impairs the quality of life. The management of neuropathic pain is challenging and should comprise alternative therapies. Researchers working on neural modulation methods in the field of optogenetics have recently referred to novel techniques that involve the activation or inhibition of signaling proteins by specific wavelengths of light. The use of optogenetics in neuropathic pain facilitates the investigation of pain pathways involved in chronic pain and has the potential for therapeutic use. Neuropathic pain is often accompanied by negative stimuli involving a broad network of brain regions. In particular, the anterior cingulate cortex (ACC) is a part of the limbic system that has highly interconnected structures involved in processing components of pain. The ACC is a key region for acute pain perception as well as the development of neuropathic pain, characterized by long-term potentiation induced in pain pathways. The exact mechanism for neuropathic pain in the ACC is unclear. Current evidence supports the potential of optogenetics methods to modulate the neuronal activity in the ACC for neuropathic pain. We anticipate the neuronal modulation in the ACC will be used widely to manage neuropathic pain.

Transplantation of human embryonic stem cells alleviates motor dysfunction in AAV2-Htt171-82Q transfected rat model of Huntington's disease.

BACKGROUND: Human embryonic stem cells (hESCs) transplantation had shown to provide a potential source of cells in neurodegenerative disease studies and lead to behavioral recovery in lentivirus transfected or, toxin-induced Huntington's disease (HD) rodent model. Here, we aimed to observe if transplantation of superparamagnetic iron oxide nanoparticle (SPION)-labeled hESCs could migrate in the neural degenerated area and improve motor dysfunction in an AAV2-Htt171-82Q transfected Huntington rat model. METHODS: All animals were randomly allocated into three groups at first: HD group, sham group, and control group. After six weeks, the animals of the HD group and sham group were again divided into two subgroups depending on animals receiving either ipsilateral or contralateral hESCs transplantation. We performed cylinder test and stepping test every two weeks after AAV2-Htt171-82Q injection and hESCs transplantation. Stem cell tracking was performed once per two weeks using T2 and T2*-weighted images at 4.7 Tesla MRI. We also performed immunohistochemistry and immunofluorescence staining to detect the presence of hESCs markers, huntingtin protein aggregations, and iron in the striatum. RESULTS: After hESCs transplantation, the Htt virus-injected rats exhibited significant behavioral improvement in behavioral tests. SPION labeled hESCs showed migration with hypointense signal in MRI. The cells were positive with ßIII-tubulin, GABA, and DARPP32. CONCLUSION: Collectively, our results suggested that hESCs transplantation can be a potential treatment for motor dysfunction of Huntington's disease.

Development of an inside-out augmented reality technique for neurosurgical navigation.

OBJECTIVE: With the advancement of 3D modeling techniques and visualization devices, augmented reality (AR)-based navigation (AR navigation) is being developed actively. The authors developed a pilot model of their newly developed inside-out tracking AR navigation system. METHODS: The inside-out AR navigation technique was developed based on the visual inertial odometry (VIO) algorithm. The Quick Response (QR) marker was created and used for the image feature-detection algorithm. Inside-out AR navigation works through the steps of visualization device recognition, marker recognition, AR implementation, and registration within the running environment. A virtual 3D patient model for AR rendering and a 3D-printed patient model for validating registration accuracy were created. Inside-out tracking was used for the registration. The registration accuracy was validated by using intuitive, visualization, and quantitative methods for identifying coordinates by matching errors. Fine-tuning and opacity-adjustment functions were developed. RESULTS: ARKit-based inside-out AR navigation was developed. The fiducial marker of the AR model and those of the 3D-printed patient model were correctly overlapped at all locations without errors. The tumor and anatomical structures of AR navigation and the tumors and structures placed in the intracranial space of the 3D-printed patient model precisely overlapped. The registration accuracy was quantified using coordinates, and the average moving errors of the x-axis and y-axis were 0.52 ± 0.35 and 0.05 ± 0.16 mm, respectively. The gradients from the x-axis and y-axis were 0.35° and 1.02°, respectively. Application of the fine-tuning and opacity-adjustment functions was proven by the videos. CONCLUSIONS: The authors developed a novel inside-out tracking-based AR navigation system and validated its registration accuracy. This technical system could be applied in the novel navigation system for patient-specific neurosurgery.

The Effect of Optogenetic Inhibition of the Anterior Cingulate Cortex in Neuropathic Pain Following Sciatic Nerve Injury.

Cortical disinhibition is the underlying pathological alteration contributing to neuropathic pain associated with peripheral nerve injury. Nerve injury resulting in disinhibition of the anterior cingulate cortex has been reported. However, the effect of optogenetic inhibition of the anterior cingulate cortex (ACC) on the sensory component of nerve injury-induced neuropathic pain has not been well studied. To investigate the feasibility of optogenetic ACC modulation, we injected an optogenetic virus or a null virus into the ACC of a nerve injury-induced neuropathic pain model. The unilateral ACC was modulated, and the optogenetic effect was measured by mechanical and thermal sensitivity tests. The assessment was performed in "pre-light off," "stimulation-yellow light on," and "post-light off" states. Optogenetic inhibition of the ACC in injury models revealed improved mechanical and thermal latencies with profound pain-relieving effects against nerve injury-induced neuropathic pain. The sensory thalamic discharge in electrophysiological in vivo recordings was also altered during laser stimulation. This finding indicates that hyperactivity of the ACC in nerve injury increases output to the spinothalamic tract through direct or indirect pathways. The direct photoinhibition of ACC neurons could play a vital role in restoring equilibrium and provide novel insight into techniques that can assuage peripheral nerve injury-induced neuropathic pain.

Pain modulation effect on motor cortex after optogenetic stimulation in shPKCγ knockdown dorsal root ganglion-compressed Sprague-Dawley rat model.

Neuropathic pain can be generated by chronic compression of dorsal root ganglion (CCD). Stimulation of primary motor cortex can disrupt the nociceptive sensory signal at dorsal root ganglion level and reduce pain behaviors. But the mechanism behind it is still implicit. Protein kinase C gamma is known as an essential enzyme for the development of neuropathic pain, and specific inhibitor of protein kinase C gamma can disrupt the sensory signal and reduce pain behaviors. Optogenetic stimulation has been emerged as a new and promising conducive method for refractory neuropathic pain. The aim of this study was to provide evidence whether optical stimulation of primary motor cortex can modulate chronic neuropathic pain in CCD rat model. Animals were randomly divided into CCD group, sham group, and control group. Dorsal root ganglion-compressed neuropathic pain model was established in animals, and knocking down of protein kinase C gamma was also accomplished. Pain behavioral scores were significantly improved in the short hairpin Protein Kinase C gamma knockdown CCD animals during optic stimulation. Ventral posterolateral thalamic firing inhibition was also observed during light stimulation on motor cortex in CCD animal. We assessed alteration of pain behaviors in pre-light off, stimulation-light on, and post-light off state. In vivo extracellular recording of the ventral posterolateral thalamus, viral expression in the primary motor cortex, and protein kinase C gamma expression in dorsal root ganglion were investigated. So, optical cortico-thalamic inhibition by motor cortex stimulation can improve neuropathic pain behaviors in CCD animal, and knocking down of protein kinase C gamma plays a conducive role in the process. This study provides feasibility for in vivo optogenetic stimulation on primary motor cortex of dorsal root ganglion-initiated neuropathic pain.

An Optimization of AAV-82Q-Delivered Rat Model of Huntington's Disease.

OBJECTIVE: No optimum genetic rat Huntington model both neuropathological using an adeno-associated virus (AAV-2) vector vector has been reported to date. We investigated whether direct infection of an AAV2 encoding a fragment of mutant huntingtin (AV2-82Q) into the rat striatum was useful for optimizing the Huntington rat model. METHODS: We prepared ten unilateral models by injecting AAV2-82Q into the right striatum, as well as ten bilateral models. In each group, five rats were assigned to either the 2×1012 genome copies (GC)/mL of AAV2-82Q (×1, low dose) or 2×1013 GC/mL of AAV2-82Q (×10, high dose) injection model. Ten unilateral and ten bilateral models injected with AAV-empty were also prepared as control groups. We performed cylinder and stepping tests 2, 4, 6, and 8 weeks after injection, tested EM48 positive mutant huntingtin aggregates. RESULTS: The high dose of unilateral and bilateral AAV2-82Q model showed a greater decrease in performance on the stepping and cylinder tests. We also observed more prominent EM48-positive mutant huntingtin aggregates in the medium spiny neurons of the high dose of AAV2-82Q injected group. CONCLUSION: Based on the results from the present study, high dose of AAV2-82Q is the optimum titer for establishing a Huntington rat model. Delivery of high dose of human AAV2-82Q resulted in the manifestation of Huntington behaviors and optimum expression of the huntingtin protein in vivo.

Optical Modulation on the Nucleus Accumbens Core in the Alleviation of Neuropathic Pain in Chronic Dorsal Root Ganglion Compression Rat Model.

OBJECTIVE: The role of the nucleus accumbens (NAc) in chronic neuropathic pain has been suggested, but the role of the NAc in dorsal root ganglion (DRG) neuropathic pain remains unclear. The objective of this study was to determine whether optogenetic stimulation of the NAc influences DRG compression-induced neuropathic pain. MATERIALS AND METHODS: We established sham or DRG lesions in female Sprague-Dawley rats by L4-5 DRG root compression, and the animals received unilateral injections of optogenetic virus in the NAc core. We employed reflexive pain tests to assess the alterations between the groups at the light on/off states. To determine thalamic firing, we performed single-unit in vivo extracellular recording. For statistical analysis, we used one- or two-way repeated-measures analysis of variance. RESULTS: Compared to sham-operated rats, chronic compressed DRG rats showed elevated behavioral sensitivity and sustained neuronal hyperexcitability in the thalamus. NAc optic stimulation improved pain behaviors and lowered thalamic discharge from ventral posterolateral thalamic nuclei. CONCLUSIONS: The NAc core impacts the reward and motivational aspects of chronic neuropathic pain influenced by limbic behaviors to thalamic discharge. Increased thalamic firing activity may result in chronic compressed DRG-induced neuropathic pain, and optogenetic neuromodulation of the NAc can ease chronic pain and thalamic discharge.

Atrophic Changes and Diffusion Abnormalities of Affected Trigeminal Nerves in Trigeminal Neuralgia Using 7-T MRI.

BACKGROUND: Magnetic resonance imaging (MRI) has been widely used for visualizing trigeminal nerves in trigeminal neuralgia. OBJECTIVE: To assess atrophy and diffusion abnormalities of affected trigeminal nerves in trigeminal neuralgia with 7-T MRI. METHODS: In this prospective study, 14 patients (mean age 49 years; range 31-64 years) with trigeminal neuralgia underwent 7-T MRI. We measured trigeminal nerve volumes along their course through the pontocerebellar cistern. We also evaluated fractional anisotropy (FA) and quantitative anisotropy (QA) values within cisternal segment and pontine nuclei of the affected-side and unaffected-side trigeminal nerves, using diffusion tensor imaging (DTI). Associations between DTI metrics and Barrow Neurological Institute (BNI) pain scores were examined. RESULTS: The volumes were significantly smaller for the affected trigeminal nerves (33.83 ± 23.12 mm3) than for the unaffected ones (47.76 ± 32.48 mm3; p = 0.008). Cisternal segment FA and QA values were significantly lower in affected trigeminal nerves than in unaffected ones. However, DTI measurements in the pontine nuclei revealed no significant differences between affected-side and unaffected-side trigeminal nerves. No DTI metrics significantly correlated with BNI pain scores. CONCLUSION: Our results suggest that 7-T MRI allows identifications of atrophy and diffusion abnormalities of trigeminal nerves in trigeminal neuralgia.

7 Tesla magnetic resonance imaging of caudal anterior cingulate and posterior cingulate cortex atrophy in patients with trigeminal neuralgia.

The cingulate cortex (CC) is a brain region that plays a key role in pain processing, but CC abnormalities are not unclear in patients with trigeminal neuralgia (TN). The purpose of this study was to determine the central causal mechanisms of TN and the surrounding brain structure in healthy controls and patients with TN using 7 Tesla (T) magnetic resonance imaging (MRI). Whole-brain parcellation in gray matter volume and thickness was assessed in 15 patients with TN and 16 healthy controls matched for sex, age, and regional variability using T1-weighted imaging. Regions of interest (ROIs) were measured in rostral anterior CC (rACC), caudal anterior CC (cACC) and posterior CC (PCC). We also investigated associations between gray matter volume or thickness and clinical symptoms, such as pain duration, Barrow Neurologic Institute (BNI) scores, offender vessel, and medications, in patients with TN. The cACC and PCC exhibited gray matter atrophy and reduced thickness between the TN and control groups. However, the rACC did not. Cortical volumes were negatively correlated with pain duration in transverse and inferior temporal areas, and thickness was also negatively correlated with pain duration in superior frontal and parietal areas. The cACC and PCC gray matter atrophy occurred in the patients with TN, and pain duration was associated with frontal, parietal, and temporal cortical regions. These results suggest that the cACC, PCC but not the rACC are associated with central pain mechanisms in TN.

7.0 Tesla MRI tractography in patients with trigeminal neuralgia.

7.0 Tesla (T) high-resolution diffusion tensor imaging (DTI) can supply information on changing microstructures in cranial nerves. We investigated DTI parameters and the feasibility of DTI criteria for diagnosing trigeminal neuralgia (TN). In this study, 14 patients (28 hemispheres) of mean age 49.0 years (range, 31-64) with TN underwent DTI using 7.0 TMRI. We compared fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) of affected-side and unaffected-side trigeminal nerves using DTI. We examined associations between DTI parameters and clinical characteristics for patients with TN. In patients with TN, affected sides showed significantly decreased FA and significantly increased MD, and RD compared with unaffected sides of trigeminal nerves. Nuclei were not significantly different among patients with TN. Barrow Neurological Institute (BNI) pain scores did not correlate with affected sides. 7.0 T DTI was useful for detecting neurovascular compression in patients with TN. The increased signal-to-noise ratio provided by 7 T MRI should be advantageous for increasing spatial resolution to detect microstructure changes to trigeminal nerves in patients with TN.

Characterization of Tetrodes Coated with Au Nanoparticles (AuNPs) and PEDOT and Their Application to Thalamic Neural Signal Detection in vivo.

Tetrodes, consisting of four twisted micro-wires can simultaneously record the number of neurons in the brain. To improve the quality of neuronal activity detection, the tetrode tips should be modified to increase the surface area and lower the impedance properties. In this study, tetrode tips were modified by the electrodeposition of Au nanoparticles (AuNPs) and dextran (Dex) doped poly (3,4-ethylenedioxythiophene) (PEDOT). The electrochemical properties were measured using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). A decrease in the impedance value from 4.3 MΩ to 13 kΩ at 1 kHz was achieved by the modified tetrodes. The cathodic charge storage capacity (CSCC) of AuNPs-PEDOT deposited tetrodes was 4.5 mC/cm2, as determined by CV measurements. The tetrodes that were electroplated with AuNPs and PEDOT exhibited an increased surface area, which reduced the tetrode impedance. In vivo recording in the ventral posterior medial (VPM) nucleus of the thalamus was performed to investigate the single-unit activity in normal rats. To evaluate the recording performance of modified tetrodes, spontaneous spike signals were recorded. The values of the L-ratio, isolation distance and signal-to-noise (SNR) confirmed that electroplating the tetrode surface with AuNPs and PEDOT improved the recording performance, and these parameters could be used to effectively quantify the spikes of each cluster.

Effect of optogenetic modulation on entopeduncular input affects thalamic discharge and behavior in an AAV2-α-synuclein-induced hemiparkinson rat model.

OBJECTIVE: Neuromodulation of the globus pallidus internus(GPi) alleviates Parkinson's disease symptoms. The primate GPi is homologous to the rat entopeduncular nucleus (EP). The aim of the present study was to determine if optogenetic modulation of the EP could alter parkinsonian behavior or thalamic discharge in a hemiparkinson rat model. METHODS: We injected an adeno-associated virus type-2 expressing α-synuclein (AAV2-α-syn) into the substantia nigra pars compacta (SNc) of the right hemisphere and confirmed parkinsonian behavior using an amphetamine-induced rotation test. Then we injected activated or inhibited neurons, using the channelrhodopsin2 (ChR2)/halorhodopsin (NpHR) system in the EP of the hemiparkinson rat model and examined downstream effects in vivo. We assessed alterations in parkinsonian behaviors using the stepping and cylinder tests before, during, and after optogenetic stimulation. RESULTS: Importantly, optogenetic inhibition of the EP improved parkinsonian motor behaviors. When we monitored thalamic neuronal activity following optogenetic neuromodulation in vivo, and we observed alterations in thalamic discharge The thalamic neuronal activity is increased for optogenetic inhibition stimulation, whereas decreased for optogenetic activation stimulation. CONCLUSIONS: Taken together, our data demonstrate that optical neuromodulation of the EP can successfully control contralateral forelimb movement and thalamic discharge in an AAV2-α-synuclein-induced hemiparkinson rat model.