Recording of single-unit activities with flexible micro-electrocorticographic array in rats for decoding of whole-body navigation.

Objective.Micro-electrocorticographic (µECoG) arrays are able to record neural activities from the cortical surface, without the need to penetrate the brain parenchyma. Owing in part to small electrode sizes, previous studies have demonstrated that single-unit spikes could be detected from the cortical surface, and likely from Layer I neurons of the neocortex. Here we tested the ability to useµECoG arrays to decode, in rats, body position during open field navigation, through isolated single-unit activities.Approach. µECoG arrays were chronically implanted onto primary motor cortex (M1) of Wistar rats, and neural recording was performed in awake, behaving rats in an open-field enclosure. The signals were band-pass filtered between 300-3000 Hz. Threshold-crossing spikes were identified and sorted into distinct units based on defined criteria including waveform morphology and refractory period. Body positions were derived from video recordings. We used gradient-boosting machine to predict body position based on previous 100 ms of spike data, and correlation analyses to elucidate the relationship between position and spike patterns.Main results.Single-unit spikes could be extracted during chronic recording fromµECoG, and spatial position could be decoded from these spikes with a mean absolute error of prediction of 0.135 and 0.090 in the x- and y- dimensions (of a normalized range from 0 to 1), and Pearson's r of 0.607 and 0.571, respectively.Significance. µECoG can detect single-unit activities that likely arise from superficial neurons in the cortex and is a promising alternative to intracortical arrays, with the added benefit of scalability to cover large cortical surface with minimal incremental risks. More studies should be performed in human related to its use as brain-machine interface.

Artificial neural network for brain-machine interface consistently produces more naturalistic finger movements than linear methods.

Brain-machine interfaces (BMI) aim to restore function to persons living with spinal cord injuries by 'decoding' neural signals into behavior. Recently, nonlinear BMI decoders have outperformed previous state-of-the-art linear decoders, but few studies have investigated what specific improvements these nonlinear approaches provide. In this study, we compare how temporally convolved feedforward neural networks (tcFNNs) and linear approaches predict individuated finger movements in open and closed-loop settings. We show that nonlinear decoders generate more naturalistic movements, producing distributions of velocities 85.3% closer to true hand control than linear decoders. Addressing concerns that neural networks may come to inconsistent solutions, we find that regularization techniques improve the consistency of tcFNN convergence by 194.6%, along with improving average performance, and training speed. Finally, we show that tcFNN can leverage training data from multiple task variations to improve generalization. The results of this study show that nonlinear methods produce more naturalistic movements and show potential for generalizing over less constrained tasks. Teaser: A neural network decoder produces consistent naturalistic movements and shows potential for real-world generalization through task variations.

Impact of subthalamic nucleus stimulation on urinary dysfunction and constipation in Parkinson's disease.

OBJECTIVE: The effect of subthalamic nucleus (STN) deep brain stimulation (DBS) on urinary dysfunction and constipation in Parkinson's disease (PD) is variable. This study aimed to identify potential surgical and nonsurgical variables predictive of these outcomes. METHODS: The authors used the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I to assess urinary dysfunction (item 10) and constipation (item 11) preoperatively and at 6-12 months postoperatively. A multiple linear regression model was used to investigate the impact of global cerebral atrophy (GCA) and active electrode contact location on the urinary dysfunction and constipation follow-up scores, controlling for age, disease duration, baseline score, motor improvement, and levodopa-equivalent dose changes. An electric field model was applied to localize the maximal-effect sites for constipation and urinary dysfunction compared with those for motor improvement. RESULTS: Among 74 patients, 23 improved, 28 deteriorated, and 23 remained unchanged for urinary dysfunction; 25 improved, 15 deteriorated, and 34 remained unchanged for constipation. GCA score and age significantly predicted urinary dysfunction follow-up score (R2 = 0.36, p < 0.001). Increased GCA and age were independently associated with worsening urinary symptoms. Disease duration, baseline constipation score, and anterior active electrode contacts in both hemispheres were significant predictors of constipation follow-up score (R2 = 0.31, p < 0.001). Higher baseline constipation score and disease duration were associated with worsening constipation; anterior active contact location was associated with improvement in constipation. CONCLUSIONS: Anterior active contact location was associated with improvement in constipation in PD patients after STN DBS. PD patients with greater GCA scores before surgery were more likely to experience urinary deterioration after DBS.

Dorsal subthalamic deep brain stimulation improves pain in Parkinson's disease.

Introduction: Inconsistent effects of subthalamic deep brain stimulation (STN DBS) on pain, a common non-motor symptom of Parkinson's disease (PD), may be due to variations in active contact location relative to some pain-reducing locus of stimulation. This study models and compares the loci of maximal effect for pain reduction and motor improvement in STN DBS. Methods: We measured Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) Part I pain score (item-9), and MDS-UPDRS Part III motor score, preoperatively and 6-12 months after STN DBS. An ordinary least-squares regression model was used to examine active contact location as a predictor of follow-up pain score while controlling for baseline pain, age, dopaminergic medication, and motor improvement. An atlas-independent isotropic electric field model was applied to distinguish sites of maximally effective stimulation for pain and motor improvement. Results: In 74 PD patients, mean pain score significantly improved after STN DBS (p = 0.01). In a regression model, more dorsal active contact location was the only significant predictor of pain improvement (R2 = 0.17, p = 0.03). The stimulation locus for maximal pain improvement was lateral, anterior, and dorsal to that for maximal motor improvement. Conclusion: STN stimulation, dorsal to the site of optimal motor improvement, improves pain. This region contains the zona incerta, which is known to modulate pain in humans, and may explain this observation.

Acute V3 Hypesthesia following Laser Interstitial Thermal Therapy for Drug-Resistant Epilepsy.

Three studies have reported trigeminal hypesthesia following temporal lobe resection. However, no cases of hypesthesia have been reported following laser interstitial thermal therapy (LITT). We report the first case of trigeminal hypesthesia as a complication of otherwise successful LITT in a patient with drug-resistant epilepsy. A 58-year-old male with drug-resistant epilepsy secondary to a left parahippocampal gyrus multinodular and vacuolating neuronal tumor underwent biopsy and MRI-guided LITT. Immediately postoperatively, the patient reported hypesthesia in the left V3 distribution, including inside the mouth and ear. At 6-month follow-up, hypesthesia was present but improving, and the patient was seizure-free. While the cerebellopontine angle and prepontine cisterns are considered thermal insulators, we hypothesize that thermal injury was conducted through these spaces to the cisternal segment of the trigeminal nerve or to the inferior V3 branch in Meckel's cave. Moreover, real-time visualization of the ablation is impacted by a blind spot at the skull base, created from bone disruption of MRI thermography.

Neuromodulation of OCD: A review of invasive and non-invasive methods.

Early research into neural correlates of obsessive compulsive disorder (OCD) has focused on individual components, several network-based models have emerged from more recent data on dysfunction within brain networks, including the the lateral orbitofrontal cortex (lOFC)-ventromedial caudate, limbic, salience, and default mode networks. Moreover, the interplay between multiple brain networks has been increasingly recognized. As the understanding of the neural circuitry underlying the pathophysiology of OCD continues to evolve, so will too our ability to specifically target these networks using invasive and noninvasive methods. This review discusses the rationale for and theory behind neuromodulation in the treatment of OCD.

Decline of verbal fluency with lateral superior frontal gyrus penetration in subthalamic nucleus deep brain stimulation for Parkinson disease.

OBJECTIVE: Verbal fluency (VF) decline is a well-recognized adverse cognitive outcome following subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinson disease (PD). The mechanisms underlying VF decline, whether from stimulation, lesioning, or both, remain unclear. This study aims to investigate the unique effects of DBS lead trajectory on VF beyond previously reported effects of active contact location. METHODS: The study population included 56 patients with idiopathic PD who underwent bilateral STN DBS. Phonemic and semantic VF scores were compared pre- and postoperatively. Features of the electrode trajectory were measured on postoperative imaging, including distance from the falx cerebri, distance from the superior frontal sulcus, and caudate nucleus penetration. The authors used t-tests, Pearson's correlation, and multiple linear regression analyses to examine the relationship between VF change and demographic, disease, and electrode trajectory variables. RESULTS: The laterality of entry within the left superior frontal gyrus (SFG) predicted greater phonemic VF decline (sr2 = 0.28, p < 0.001) after controlling for active contact location. VF change did not differ by the presence of caudate nucleus penetration in either hemisphere (p > 0.05). CONCLUSIONS: Lateral penetration of the SFG in the left hemisphere is associated with worsening phonemic VF and has greater explanatory power than active contact location. This may be explained by lesioning of the lateral SFG-Broca area pathway, which is implicated in language function.

Large Primary Transethmoidal Encephalocele Presenting in an Adult.

Transethmoidal encephaloceles are rare and most commonly present at birth with congenital abnormalities, cerebrospinal fluid rhinorrhea, or visual symptoms. Here, we report the case of a 43-year-old presenting with longstanding headache, blurry vision, anosmia, and rhinorrhea. Magnetic resonance imaging confirmed a transethmoidal encephalocele. The patient underwent craniotomy for resection of the encephalocele and repair of the cribriform defect. The postoperative course was uneventful, and the patient was discharged home with the resolution of rhinorrhea and headache. This report highlights a rare case of primary transethmoidal encephalocele undiagnosed until adulthood despite longstanding symptoms and successful treatment with resolution of symptoms.

Acute low frequency dorsal subthalamic nucleus stimulation improves verbal fluency in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder that results in movement-related dysfunction and has variable cognitive impairment. Deep brain stimulation (DBS) of the dorsal subthalamic nucleus (STN) has been shown to be effective in improving motor symptoms; however, cognitive impairment is often unchanged, and in some cases, worsened particularly on tasks of verbal fluency. Traditional DBS strategies use high frequency gamma stimulation for motor symptoms (∼130 Hz), but there is evidence that low frequency theta oscillations (5-12 Hz) are important in cognition. METHODS: We tested the effects of stimulation frequency and location on verbal fluency among patients who underwent STN DBS implantation with externalized leads. During baseline cognitive testing, STN field potentials were recorded and the individual patients' peak theta frequency power was identified during each cognitive task. Patients repeated cognitive testing at five different stimulation settings: no stimulation, dorsal contact gamma (130 Hz), ventral contact gamma, dorsal theta (peak baseline theta) and ventral theta (peak baseline theta) frequency stimulation. RESULTS: Acute left dorsal peak theta frequency STN stimulation improves overall verbal fluency compared to no stimulation and to either dorsal or ventral gamma stimulation. Stratifying by type of verbal fluency probes, verbal fluency in episodic categories was improved with dorsal theta stimulation compared to all other conditions, while there were no differences between stimulation conditions in non-episodic probe conditions. CONCLUSION: Here, we provide evidence that dorsal STN theta stimulation may improve verbal fluency, suggesting a potential possibility of integrating theta stimulation into current DBS paradigms to improve cognitive outcomes.

Cognitive outcomes following vagus nerve stimulation, responsive neurostimulation and deep brain stimulation for epilepsy: A systematic review.

BACKGROUND: The cognitive impacts of resective surgery for epilepsy have been well-studied. While seizure outcomes for less invasive, neuromodulatory treatments are promising, there is a paucity of data for cognitive outcomes. METHODS: Medline, EMBASE, and the Cochrane Library were searched on November 2019. Inclusion criteria were studies reporting cognitive outcomes following chronic (>6 months) vagus nerve stimulation (VNS), deep brain stimulation (DBS) and responsive neurostimulation (RNS) for epilepsy in at least five patients. Studies reporting acute on-off effects of stimulation were also included. Studies were screened, extracted of data, and assessed for bias using the Joanna Briggs Institute Critical Appraisal Tools by two independent reviewers. Prospero ID: CRD42020184432. RESULTS: Of 8443 studies screened, 29 studies were included. Nineteen investigated the effects of chronic stimulation (11 VNS, 6 DBS, 2 RNS): 10 (53 %) reported no change compared to preoperative baseline; 8 (42 %) reported some improvement in one or more cognitive domain; 1 (5%) reported decline. Ten investigated the effects of acute stimulation (5 VNS, 5 DBS): 3 (30 %) reported no change; 4 reported improvement (40 %); 3 (30 %) reported decline. Eight (28 %) did not report statistical analysis. CONCLUSIONS: Long-term cognitive outcomes are at least stable following VNS, DBS and RNS. Acute effects of stimulation are less clear. However, data are limited by number, size, and quality. More robust evidence is needed to properly assess the cognitive effects of each of these treatments.

Cerebrovascular bypass for ruptured aneurysms: A case series.

In patients with aneurysmal subarachnoid hemorrhage (aSAH) unfavorable for endovascular or traditional open surgical techniques, surgical revascularization strategies comprise one of remaining limited options. There is nonetheless a paucity of data on the safety and efficacy of bypass in aSAH. In this study, we aimed to investigate complications and outcomes in a cohort of patients with aSAH treated with bypass. A prospective single-surgeon database of consecutive patients treated for aSAH between 2013 and 2018 was retrospectively analyzed. Complications and functional status at discharge were recorded and analyzed for the patients that underwent bypass surgery. Forty patients with aSAH were treated with bypass surgery (23 extracranial-intracranial; 17 intracranial-intracranial). All-cause perioperative mortality was 13% (6 patients). At discharge and at mean 14-month follow up, respectively, 16/40 (40%) and 16/25 (64%) of patients achieved a Glasgow Outcome Score of 4-5. All-cause, in-hospital complications occurred in 28 patients (70%), of which any ischemic complication occurred in 20 patients (50%), 7 (18%) being open surgical complications. This work represents the largest modern series of bypass for aSAH to date. In cases of aSAH unfavorable for endovascular intervention or traditional open surgical techniques, bypass remains a viable option in this complex group of patients.

Gray Matter Atrophy: The Impacts of Resective Surgery and Vagus Nerve Stimulation in Drug-Resistant Epilepsy.

BACKGROUND: There is great concern for cognitive function after resective temporal lobe surgery for drug-resistant epilepsy. However, few studies have investigated postoperative anatomical changes, and the downstream effects of surgery are poorly understood. This study investigated volumetric changes after resective surgery and vagus nerve stimulation (VNS) for epilepsy. METHODS: Preoperative and latest postoperative (mean, 28 months) structural T1 magnetic resonance imaging scans were retrospectively obtained for 43 patients: 27 temporal lobe resections (TLRs), 6 extratemporal lobe resections, and 10 VNS, undergoing surgery for drug-resistant epilepsy between 2012 and 2017. Automated volumetric analyses of predefined cortical gray matter and subcortical structures were performed. Preoperative and postoperative volumes were compared, and the effects of age, gender, operation type, resection laterality, selectivity, time since surgery, and seizure outcome on volumetric changes were analyzed. RESULTS: After TLRs, there were reductions in contralateral hemispheric gray matter, temporal lobe, entorhinal cortex, parahippocampal, superior temporal, middle temporal, inferior temporal (P = 0.02), lingual, fusiform, precentral, paracentral, postcentral, pericalcarine gyri, and ipsilateral superior parietal gyrus. After VNS, there was bilateral atrophy in the thalamus, putamen, cerebellum, rostral anterior cingulate, posterior cingulate, medial orbitofrontal, paracentral, fusiform, and transverse temporal gyri. There was a significant effect of surgery type but no effect of age, gender, operation type, resection laterality, selectivity, time since surgery, and seizure outcome on contralateral hippocampal gray matter change. CONCLUSION: This is the first study to demonstrate volumetric decreases in temporal and connected regions after TLRs and VNS. These results provide interesting insight into functional network changes.

Cognitive effects of theta frequency bilateral subthalamic nucleus stimulation in Parkinson's disease: A pilot study.

BACKGROUND: There is significant evidence for cognitive decline following deep brain stimulation (DBS). Current stimulation paradigms utilize gamma frequency stimulation for optimal motor benefits; however, little has been done to optimize stimulation parameters for cognition. Recent evidence implicates subthalamic nucleus (STN) theta oscillations in executive function, and theta oscillations are well-known to relate to episodic memory, suggesting that theta frequency stimulation could potentially improve cognition in Parkinson's disease (PD). OBJECTIVE: To evaluate the acute effects of theta frequency bilateral STN stimulation on executive function in PD versus gamma frequency and off, as well as investigate the differential effects on episodic versus nonepisodic verbal fluency. METHODS: Twelve patients (all males, mean age 60.8) with bilateral STN DBS for PD underwent a double-blinded, randomized cognitive testing during stimulation at (1) 130-135 Hz (gamma), (2) 10 Hz (theta) and (3) off. Executive functions and processing speed were evaluated using verbal fluency tasks (letter, episodic category, nonepisodic category, and category switching), color-word interference task, and random number generation task. Performance at each stimulation frequency was compared within subjects. RESULTS: Theta frequency significantly improved episodic category fluency compared to gamma, but not compared to off. There were no significant differences between stimulation frequencies in other tests. CONCLUSION: In this pilot trial, our results corroborate the role of theta oscillations in episodic retrieval, although it is unclear whether this reflects direct modulation of the medial temporal lobe and whether similar effects can be found with more canonical memory paradigms. Further work is necessary to corroborate our findings and investigate the possibility of interleaving theta and gamma frequency stimulation for concomitant motor and cognitive effects.

Deep Brain Stimulation for Alzheimer's Disease: Tackling Circuit Dysfunction.

OBJECTIVES: Treatments for Alzheimer's disease are urgently needed given its enormous human and economic costs and disappointing results of clinical trials targeting the primary amyloid and tau pathology. On the other hand, deep brain stimulation (DBS) has demonstrated success in other neurological and psychiatric disorders leading to great interest in DBS as a treatment for Alzheimer's disease. MATERIALS AND METHODS: We review the literature on 1) circuit dysfunction in Alzheimer's disease and 2) DBS for Alzheimer's disease. Human and animal studies are reviewed individually. RESULTS: There is accumulating evidence of neural circuit dysfunction at the structural, functional, electrophysiological, and neurotransmitter level. Recent evidence from humans and animals indicate that DBS has the potential to restore circuit dysfunction in Alzheimer's disease, similarly to other movement and psychiatric disorders, and may even slow or reverse the underlying disease pathophysiology. CONCLUSIONS: DBS is an intriguing potential treatment for Alzheimer's disease, targeting circuit dysfunction as a novel therapeutic target. However, further exploration of the basic disease pathology and underlying mechanisms of DBS is necessary to better understand how circuit dysfunction can be restored. Additionally, robust clinical data in the form of ongoing phase III clinical trials are needed to validate the efficacy of DBS as a viable treatment.

An Expedited Transition to the Back Wall Suturing for Side-to-Side In Situ Microvascular Anastomosis: A Technique Update.

BACKGROUND: The side-to-side in situ microvascular anastomosis is an important tool in the cerebrovascular neurosurgeon's armamentarium. The execution of the side-to-side anastomosis, however, can be limited by the inability to acquire sufficient visualization and approximation of the recipient and donor vessels. OBJECTIVE: To expedite the transition to the back wall suturing of the donor and recipient vessels during side-to-side in situ microvascular anastomosis. METHODS: Incorporation of the first suture throw from the outside to the inside of the vessel lumen with the initial stay suture at the proximal apex of the arteriotomy is described. The apical knot is tied between one limb of the resultant loop and the free end of the suture. The remainder of side-to-side anastomosis can then be completed in a standard fashion starting from the inside of the lumen. RESULTS: This modification allows for an expedited transition to the back wall suturing of the 2 arterial segments and avoids difficulties associated with taking the first bite from behind the knot at the proximal apex of the arteriotomy or the transfer of the needle between the approximated vessels. This updated technique is illustrated with a case example, illustration, and video. CONCLUSION: This technical modification for the side-to-side anastomosis helps optimize microsurgical efficiency by limiting needle, suture, and vessel handling after the initial suture placement, which has classically been a challenge of this bypass.

Conservative Management of Type II Odontoid Fractures in Older People: A Retrospective Observational Comparison of Osseous Union Versus Nonunion.

BACKGROUND: Type II odontoid fractures are a common cervical fracture in older people. Lower osseous-union rates are reported in those treated conservatively compared to surgically; however, the clinical relevance of a nonunion is unknown. OBJECTIVE: To compare pain, disability, and quality of life in older people following conservative management of type II odontoid fractures demonstrating osseous-union and nonunion. METHODS: Electronic records were searched from 2008 to 2018 for adults ≥65 yr with type II odontoid fracture, managed in a semi-rigid collar. Clinical and demographic data were retrieved from electronic patient notes. Surviving patients were invited to complete questionnaires to assess pain, disability, and quality of life. Ethical approval was granted. RESULTS: A total of 125 patients were identified: 36 (29%) demonstrated osseous-union, 89 (71%) had nonunion, of which 33 (40%) had radiological instability. Mean age at fracture was 84 yr (osseous-union 83 yr; nonunion 84 yr). A total of 53 had deceased (41 nonunion). Median length of survival was 77 mo for osseous-union vs 50 mo for nonunion; P = .02. No patient developed myelopathy during the follow-up period. Questionnaire response rate was 39 (58%). There were no statistically significant differences between the groups in terms of pain, disability, or quality of life (P > .05). Both groups reported mild disability and pain but low quality of life. CONCLUSION: Management with a semi-rigid collar in older people with type II odontoid fracture is associated with low levels of pain and disability without statistically significant differences between those demonstrating osseous-union or stable or unstable nonunions. Conservative management appears to be a safe treatment for older people with type II fractures.

Bypass and Deconstructive Technique for Hunt and Hess Grade 3-5 Aneurysmal Subarachnoid Hemorrhage Deemed Unfavorable for Endovascular Treatment: Case Series of Outcomes and Comparison with Clipping.

BACKGROUND: Intracranial bypass to treat ruptured aneurysms has been well described in the literature but is largely deferred in patients with higher Hunt and Hess (H & H) grades due to complexity and length of surgery, risk of inducing vasospasm, and poor prognosis. However, there is a paucity of data and no direct comparison with more traditional open surgical techniques. This study investigated outcomes in patients with H & H grade 3-5 aneurysmal subarachnoid hemorrhage (aSAH) unfavorable for stand-alone endovascular treatment managed with bypass compared with direct surgical clipping. METHODS: A prospective database of patients treated for aSAH with H & H grade 3-5 between 2013 and 2018 was retrospectively analyzed. Complications and functional status at discharge and latest follow-up were compared between patients who underwent bypass surgery versus direct clipping. RESULTS: Twenty-three patients underwent revascularization, and 60 underwent clipping alone. There were no significant differences in all-cause 30-day mortality (15% vs. 16%; P = 0.97) or Glasgow Outcome Scale and modified Rankin Scale at discharge or median 8-month follow-up (P > 0.67). There was a higher overall stroke rate with revascularization (P = 0.004), specifically endovascular treatment-related stroke (P = 0.049), with no difference in surgical (P = 0.47) or vasospasm-related stroke (P = 0.53). There were no differences in overall complications, medical complications, seizures, reruptures, hydrocephalus, or perioperative death (P > 0.05). CONCLUSIONS: Bypass is a viable option for patients presenting with higher H & H grade aSAH deemed unfavorable for stand-alone endovascular therapy. Despite obvious differences in aneurysm complexity and a higher risk of stroke, functional outcomes with revascularization can be comparable with clipping in this high-risk patient cohort.