Coherence Between the Subthalamic Nucleus and the Primary Motor Cortex in Patients With Parkinson’s Disease

proposed previously as a potential approach to enhance cortical excitability in surviving, perilesional cortical regions and promote motor rehabilitation after a stroke. METHODS: 13 rats (7 naÏve and 6 stroke) were implanted unilaterally with a 9 channel recording electrode in the DN (ipsilateral to dominate forepaw) and cortical EEG screws (contralateral to dominate forepaw) were placed over the perilesional area. LFPs were recorded from the DN and motor cortex during a reach/pull task for 4 weeks after surgery. RESULTS: At a 25g force threshold, DN LFPs were diminished in the 8-12 hz in the pre-movement and movement phase in stroke rats compared with naÏve rats. At a 5g force threshold, 8-12 hz LFPs in the DN were significantly diminished in the stroke animals relative to naive during the pre-movement and movement phase (p < .05). At a 50g force threshold, cortical 1.5-4 hz oscillations were significantly diminished during the pre-movement and movement phase in stroke rats compared to naÏve rats (p < .05). CONCLUSION: Diminished 8-12 hz reach-related LFP activity in the DN of stroke rats relative to naÏve rats during the pre-movement and movement phase of a reaching task, may function as a potential predefined trigger for the onset of deep brain stimulation as a therapeutic intervention to promote motor rehabilitation for chronic post-stroke hemiparesis.


Joao P. Souza de Castro
INTRODUCTION: DBS is established as a safe and effective treatment for Parkinson's Disease (PD). The development of second generation stimulators based on closed loop systems is dependent upon deeper understanding of the cortical control of motricity and its coupling with STN oscillations.
METHODS: Experimental study on human subjects involving 10 patients with idiopathic PD with indication for deep brain stimulation implants into the STN. Primary motor area of the hands were identified preoperatively with fMRI. Corkscrew electrodes were implanted in the scalp to obtain C3-Cz and C4-Cz derivations of the EEG. Needle electrodes were implanted into the thenar and hypothenar muscles of both hands to record motor evoked potentials and voluntary myoelectric activity. At the time of implantation of the definitive macro-electrodes, the best contacts were connected to the electrophysiological monitoring device to record STN local field potentials (LFP) from 1 side at a time. During the next 3 minutes, the patient was asked to perform closing and opening movements of the hand contralateral to the implant. Simultaneously recordings of hand-EMG, EEG signals from M1, and STN field potentials were acquired for off line analysis.
RESULTS: Our data indicate that during epochs of hand movements, theta and beta range components of the EEG related to M1 were significantly increased as compared with rest epochs. Additionally, we demonstrated that, during movement, the cross correlation between STN-LFP and M1 significantly increased (p < 0.001).
CONCLUSION: Movement control is highly dependent upon theta and beta EEG components and upon a high coherence between STN and M1 specifically occurring during movement. The development of closed-loop stimulation devices should consider this physiology to reach better results. To date, the safety and efficacy of RNS have not been fully studied due to the lack of prospective data.
METHODS: We performed a retrospective analysis of prospectively collected data of DRE patients who underwent RNS implantation between September 2015-December 2020 at our Institution. Patients were followed postoperatively to evaluate seizure-freedom and complications. For each patient, response to RNS was determined as an overall percentage based on the relative reduction in seizure duration/severity, medication requirements and post-ictal state.
CONCLUSION: RNS achieved = 50% seizure control in ∼70% of patients. Infections and tract-hemorrhages are the most common complications, but rarely require re-intervention. Seizure-freedom after RNS implantation may be significantly lower in patients affected by aggressive epileptogenic syndromes since a young age, and those who have failed to respond to >5 drugs and prior surgical interventions. is a well stablished therapy for Parkinson's disease (PD). Initial programing of the DBS electrodes may take up to 2 hours in order to determine the contact(s) with the best and worse therapeutic response and thresholds for side effects. Furthermore novel directional electrodes have additional contacts that increase complexity and time to the selection. New image processing techniques allows reconstruction and visualisation of the DBS electrode and adjacent structures in a tridimensional space as well as modeling of the volume of tissue activation (VTA) which in turns helps to infer which contact(s) could be best for the stimulation.
METHODS: Forty-four electrodes were evaluated; directional contacts were initially reviewed as a ring. The images were processed using two different methods 1) The spatial position and distance of each electrode contact was assessed in a normalized space with respect to the STN, motor portion of the STN (mSTN) and the corticospinal tract (CST) using the open source toolbox Lead-DBS; 2) The relation of the electrode contacts with the STN was visualized using the Boston Scientific GuideTM XT clinical software which is based on automatic anatomical segmentation. Both methods were independently used to select the best (positive) and worst (negative) stimulation contacts and then compared with the final stimulation plan.
RESULTS: A chi-square analysis demonstrated a significant association between the IBP and the final therapeutic configuration (p<0.05). The test sensitivity was 95%-97.3%, specificity 85.7%-83.87%, positive predictive value 86.3%-87.8%, negative predictive value 94.7%-96.3%, and accuracy 90.2%-91.2% using the research and clinical methods respectively. In a subsequent analysis the selection of the directional contact(s) was investigated in 5 patients (6 electrodes) using current steering. In 89%-78% of the cases the contact(s) selected based on the IBP was part of the final configuration.
CONCLUSION: An Imaged-based programing plan could be used as an initial guide to predict the best electrode configuration in order to reduce the programing time, this may translate in better use of hospital resources, improve the patient comfort and may avoid further adjustments in programing.

The Role of the Mid Fusiform Gyrus in Lexical Retrieval
Kathryn Snyder; Cristian Donos; Kiefer Forseth; Patrick Rollo; Joshua Breier; Simon Fischer-Baum; Nitin Tandon, MD INTRODUCTION: Temporal lobe resections for epilepsy or neoplasms often result in significant confrontation naming decline. This can be socio-economically disabling and prevent patients from returning to independent functioning. While the exact substrates responsible are unknown, it was previously assumed that injury to the superior temporal gyrus or resection size predicts these declines. A clear understanding of the most critical constituents might influence surgical strategies to minimize language declines. METHODS: Data were obtained from 95 patients who underwent surgical resection in the dominant left temporal lobe for medicationresistant epilepsy. Patients underwent neuropsychological testing and MRI prior to and 6 months following surgery. Lesion masks were traced on postoperative MRIs and aligned to a normative space. The effects of preoperative scores and seizure outcomes were removed from postoperative scores via linear regression. VLSM using multivariate support vector regression was used to assess postoperative test scores. Beta maps were converted to p values and corrected using a permutation-based cluster level correction. Additionally, a surface-based mixed-effects multilevel analysis was used to estimate broadband gamma activity during picture naming across a subset of subjects with ECoG recordings, and results were integrated with VLSM. Lastly, fMRI (picture naming) was used to assess SNR in significant regions.
RESULTS: VLSM analysis revealed that the loss of basal temporal regions was associated with a prominent decline in BNT scores (p < 0.005). Similarly, ECoG analysis showed a significant increase in activity in the mid fusiform gyrus (mFus) immediately preceding articulation. Many of these voxels were associated with low SNR on fMRI, perhaps explaining why this region has been under-appreciated as the locus responsible for postoperative deficits.
CONCLUSION: The importance of the ventral temporal cortex in lexical access is shown using multivariate VLSM and supported with ECoG. While it has previously been assumed that mFus lesions do not cause pervasive impairment, our data and recent work (FATES study) argue against this and support the role of the mFus as a critical semantic access hub.

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Defining the Optimal Thermal Parameters for Subthreshold Testing With Focused Ultrasound Vibhor Krishna, MD; Francesco Sammartino, MD; John W. Snell, PhD; Matthew Eames INTRODUCTION: Focused ultrasound ablation (FUSA) relies on accurate subthreshold testing to physiologically explore the presumed target before permanent ablation. However, the optimal thermal parameters for subthreshold testing (i.e., thermal dose and spot size thresholds) are not yet defined.
METHODS: We performed a retrospective analysis of intraoperative testing data of essential tremor patients undergoing FUSA. Sonications with a thermal dose of less than 25 cumulative equivalent minutes (CEM) were classified as sub-threshold. The intraoperative writing samples were independently rated by two raters using the clinical rating scale for tremor. The association between thermal dose and tremor scores was statistically analyzed, and the thermal dose and spot size thresholds for tremor improvement were computed using leave-one-out cross-validation analysis.
RESULTS: From the 331 pairs of sonications and tremor assessments, 97 sonications were classified as subthreshold sonications. Intraoperative tremor improvement was observed in 23 (24%) subthreshold sonications with a median tremor improvement of 20% (interquartile range = 41.6) from the baseline. The thermal dose threshold for tremor improvement was 0.67 CEM (equivalent to 30 seconds thermal exposure at 430C). The spot size threshold for tremor improvement was 2.46 mm. VIM was exposed to TN thermal dose during sub-ablative and ablative sonications.
CONCLUSION: The optimal thermal dose and spot size thresholds for subthreshold testing are significantly higher than the current FUSA standard-of-care. We recommend long duration (>30 seconds), subthreshold sonications for intraoperative testing during FUSA. Future