The interictal suppression hypothesis is the dominant differentiator of seizure onset zones in focal epilepsy.

Successful surgical treatment of drug-resistant epilepsy traditionally relies on the identification of seizure onset zones (SOZs). Connectome-based analyses of electrographic data from stereo electroencephalography (SEEG) may empower improved detection of SOZs. Specifically, connectome-based analyses based on the Interictal Suppression Hypothesis (ISH) posit that when the patient is not having a seizure, SOZs are inhibited by non-SOZs through high inward connectivity and low outward connectivity. However, it is not clear whether there are other motifs that can better identify potential SOZs. Thus, we sought to use unsupervised machine learning to identify network motifs that elucidate SOZs and investigate if there is another motif that outperforms the ISH. Resting-state SEEG data from 81 patients with drug-resistant epilepsy undergoing a pre-surgical evaluation at Vanderbilt University Medical Center were collected. Directed connectivity matrices were computed using the alpha band (8-12Hz). Principal component analysis (PCA) was performed on each patient's connectivity matrix. Each patient's components were analyzed qualitatively to identify common patterns across patients. A quantitative definition was then used to identify the component that most closely matched the observed pattern in each patient. A motif characteristic of the Interictal Suppression Hypothesis (high-inward and low-outward connectivity) was present in all individuals and found to be the most robust motif for identification of SOZs in 64/81 (79%) patients. This principal component demonstrated significant differences in SOZs compared to non-SOZs. While other motifs for identifying SOZs were present in other patients, they differed for each patient, suggesting that seizure networks are patient specific, but the ISH is present in nearly all networks. We discovered that a potentially suppressive motif based on the Interictal Suppression Hypothesis was present in all patients, and it was the most robust motif for SOZs in 79% of patients. Each patient had additional motifs that further characterized SOZs, but these motifs were not common across all patients. This work has the potential to augment clinical identification of SOZs to improve epilepsy treatment.

Corticostriatal beta oscillation changes associated with cognitive function in Parkinson's disease.

Cognitive impairment is the most frequent non-motor symptom in Parkinson's disease and is associated with deficits in a number of cognitive functions including working memory. However, the pathophysiology of Parkinson's disease cognitive impairment is poorly understood. Beta oscillations have previously been shown to play an important role in cognitive functions including working memory encoding. Decreased dopamine in motor cortico-striato-thalamo-cortical (CSTC) circuits increases the spectral power of beta oscillations and results in Parkinson's disease motor symptoms. Analogous changes in parallel cognitive CSTC circuits involving the caudate and dorsolateral prefrontal cortex (DLPFC) may contribute to Parkinson's disease cognitive impairment. The objective of our study is to evaluate whether changes in beta oscillations in the caudate and DLPFC contribute to cognitive impairment in Parkinson's disease patients. To investigate this, we used local field potential recordings during deep brain stimulation surgery in 15 patients with Parkinson's disease. Local field potentials were recorded from DLPFC and caudate at rest and during a working memory task. We examined changes in beta oscillatory power during the working memory task as well as the relationship of beta oscillatory activity to preoperative cognitive status, as determined from neuropsychological testing results. We additionally conducted exploratory analyses on the relationship between cognitive impairment and task-based changes in spectral power in additional frequency bands. Spectral power of beta oscillations decreased in both DLPFC and caudate during working memory encoding and increased in these structures during feedback. Subjects with cognitive impairment had smaller decreases in caudate and DLPFC beta oscillatory power during encoding. In our exploratory analysis, we found that similar differences occurred in alpha frequencies in caudate and theta and alpha in DLPFC. Our findings suggest that oscillatory power changes in cognitive CSTC circuits may contribute to cognitive symptoms in patients with Parkinson's disease. These findings may inform the future development of novel neuromodulatory treatments for cognitive impairment in Parkinson's disease.

The Interictal Suppression Hypothesis in focal epilepsy: network-level supporting evidence.

Why are people with focal epilepsy not continuously having seizures? Previous neuronal signalling work has implicated gamma-aminobutyric acid balance as integral to seizure generation and termination, but is a high-level distributed brain network involved in suppressing seizures? Recent intracranial electrographic evidence has suggested that seizure-onset zones have increased inward connectivity that could be associated with interictal suppression of seizure activity. Accordingly, we hypothesize that seizure-onset zones are actively suppressed by the rest of the brain network during interictal states. Full testing of this hypothesis would require collaboration across multiple domains of neuroscience. We focused on partially testing this hypothesis at the electrographic network level within 81 individuals with drug-resistant focal epilepsy undergoing presurgical evaluation. We used intracranial electrographic resting-state and neurostimulation recordings to evaluate the network connectivity of seizure onset, early propagation and non-involved zones. We then used diffusion imaging to acquire estimates of white-matter connectivity to evaluate structure-function coupling effects on connectivity findings. Finally, we generated a resting-state classification model to assist clinicians in detecting seizure-onset and propagation zones without the need for multiple ictal recordings. Our findings indicate that seizure onset and early propagation zones demonstrate markedly increased inwards connectivity and decreased outwards connectivity using both resting-state (one-way ANOVA, P-value = 3.13 × 10-13) and neurostimulation analyses to evaluate evoked responses (one-way ANOVA, P-value = 2.5 × 10-3). When controlling for the distance between regions, the difference between inwards and outwards connectivity remained stable up to 80 mm between brain connections (two-way repeated measures ANOVA, group effect P-value of 2.6 × 10-12). Structure-function coupling analyses revealed that seizure-onset zones exhibit abnormally enhanced coupling (hypercoupling) of surrounding regions compared to presumably healthy tissue (two-way repeated measures ANOVA, interaction effect P-value of 9.76 × 10-21). Using these observations, our support vector classification models achieved a maximum held-out testing set accuracy of 92.0 ± 2.2% to classify early propagation and seizure-onset zones. These results suggest that seizure-onset zones are actively segregated and suppressed by a widespread brain network. Furthermore, this electrographically observed functional suppression is disproportionate to any observed structural connectivity alterations of the seizure-onset zones. These findings have implications for the identification of seizure-onset zones using only brief electrographic recordings to reduce patient morbidity and augment the presurgical evaluation of drug-resistant epilepsy. Further testing of the interictal suppression hypothesis can provide insight into potential new resective, ablative and neuromodulation approaches to improve surgical success rates in those suffering from drug-resistant focal epilepsy.

Disparities in Access to Deep Brain Stimulation for Parkinson's Disease and Proposed Interventions: A Literature Review.

BACKGROUND: Deep brain stimulation (DBS) is an effective therapy for Parkinson's disease (PD), but disparities exist in access to DBS along gender, racial, and socioeconomic lines. SUMMARY: Women are underrepresented in clinical trials and less likely to undergo DBS compared to their male counterparts. Racial and ethnic minorities are also less likely to undergo DBS procedures, even when controlling for disease severity and other demographic factors. These disparities can have significant impacts on patients' access to care, quality of life, and ability to manage their debilitating movement disorders. KEY MESSAGES: Addressing these disparities requires increasing patient awareness and education, minimizing barriers to equitable access, and implementing diversity and inclusion initiatives within the healthcare system. In this systematic review, we first review literature discussing gender, racial, and socioeconomic disparities in DBS access and then propose several patient, provider, community, and national-level interventions to improve DBS access for all populations.

Global Economic Evaluation of the Reported Costs of Deep Brain Stimulation.

INTRODUCTION: Despite the known benefits of deep brain stimulation (DBS), the cost of the procedure can limit access and can vary widely. Our aim was to conduct a systematic review of the reported costs associated with DBS, as well as the variability in reporting cost-associated factors to ultimately increase patient access to this therapy. METHODS: A systematic review of the literature for cost of DBS treatment was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and Embase databases were queried. Olsen & Associates (OANDA) was used to convert all reported rates to USD. Cost was corrected for inflation using the US Bureau of Labor Statistics Inflation Calculator, correcting to April 2022. RESULTS: Twenty-six articles on the cost of DBS surgery from 2001 to 2021 were included. The median number of patients across studies was 193, the mean reported age was 60.5 ± 5.6 years, and median female prevalence was 38.9%. The inflation- and currency-adjusted mean cost of the DBS device was USD 21,496.07 ± USD 8,944.16, the cost of surgery alone was USD 14,685.22 ± USD 8,479.66, the total cost of surgery was USD 40,942.85 ± USD 17,987.43, and the total cost of treatment until 1 year of follow-up was USD 47,632.27 ± USD 23,067.08. There were no differences in costs observed across surgical indication or country. CONCLUSION: Our report describes the large variation in DBS costs and the manner of reporting costs. The current lack of standardization impedes productive discourse as comparisons are hindered by both geographic and chronological variations. Emphasis should be put on standardized reporting and analysis of reimbursement costs to better assess the variability of DBS-associated costs in order to make this procedure more cost-effective and address areas for improvement to increase patient access to DBS.

Intraoperative physiology augments atlas-based data in awake deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) is commonly performed with patients awake to perform intraoperative microelectrode recordings and/or macrostimulation testing to guide final electrode placement. Supplemental information from atlas-based databases derived from prior patient data and visualised as efficacy heat maps transformed and overlaid onto preoperative MRIs can be used to guide preoperative target planning and intraoperative final positioning. Our quantitative analysis of intraoperative testing and corresponding changes made to final electrode positioning aims to highlight the value of intraoperative neurophysiological testing paired with image-based data to optimise final electrode positioning in a large patient cohort. METHODS: Data from 451 patients with movement disorders treated with 822 individual DBS leads at a single institution from 2011 to 2021 were included. Atlas-based data was used to guide surgical targeting. Intraoperative testing data and coordinate data were retrospectively obtained from a large patient database. Medical records were reviewed to obtain active contact usage and neurologist-defined outcomes at 1 year. RESULTS: Microelectrode recording firing profiles differ per track, per target and inform the locations where macrostimulation testing is performed. Macrostimulation performance correlates with the final electrode track chosen. Centroids of atlas-based efficacy heat maps per target were close in proximity to and may predict active contact usage at 1 year. Overall, patient outcomes at 1 year were improved for patients with better macrostimulation response. CONCLUSIONS: Atlas-based imaging data is beneficial for target planning and intraoperative guidance, and in conjunction with intraoperative neurophysiological testing during awake DBS can be used to individualize and optimise final electrode positioning, resulting in favourable outcomes.

Depression Scores following Ventral Intermediate Nucleus Deep Brain Stimulation for Essential Tremor: A Meta-Analysis.

BACKGROUND: Essential tremor (ET) patients present with both motor and non-motor symptoms including depression. Although deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is used to treat motor symptoms of ET, there is no consensus as to how VIM DBS influences non-motor symptoms, specifically depression. OBJECTIVE: The objective of this study was to conduct a meta-analysis of available studies investigating change in pre- to postoperative depression scores as measured by Beck Depression Inventory (BDI) in ET patients receiving VIM DBS. METHODS: Inclusion criteria were randomized control trials or observational studies of patients undergoing unilateral/bilateral VIM DBS. Non-ET patients, case reports, patients <18 years old, only non-VIM electrode placement, non-English articles, and abstracts were excluded. The primary outcome was change in BDI score from the preoperative time point to the last available follow-up. Pooled estimates of overall effect for BDI standardized mean difference were calculated using random effects models with the inverse variance method. RESULTS: Seven studies divided into eight cohorts for a total of 281 ET patients met inclusion criteria. Pooled preoperative BDI score was 12.44 (95% CI [6.63-18.25]). A statistically significant decrease in depression scores was observed postoperatively (SMD = -0.29, 95% CI [-0.46 to -0.13], p = 0.0006). Pooled postoperative BDI score was 9.18 (95% CI [4.98-13.38]). A supplementary analysis which included an additional study with an estimated standard deviation at last follow-up was conducted. There was also a statistically significant decrease in depression postoperatively (9 cohorts, n = 352, SMD = -0.31, 95% CI [-0.46 to -0.16], p < 0.0001). CONCLUSIONS: Both quantitative and qualitative analyses of the existing literature suggest that VIM DBS improves depression postoperatively among ET patients. These results may guide surgical risk-benefit analysis and counseling for ET patients undergoing VIM DBS.

Microscale Physiological Events on the Human Cortical Surface.

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.

Advanced Imaging in Psychiatric Neurosurgery: Toward Personalized Treatment.

OBJECTIVES: Our aim is to review several recent landmark studies discussing the application of advanced neuroimaging to guide target selection in deep brain stimulation (DBS) for psychiatric disorders. MATERIALS AND METHODS: We performed a PubMed literature search of articles related to psychiatric neurosurgery, DBS, diffusion tensor imaging, probabilistic tractography, functional magnetic resonance imaging (MRI), and blood oxygen level-dependent activation. Relevant articles were included in the review. RESULTS: Recent advances in neuroimaging, namely the use of diffusion tensor imaging, probabilistic tractography, functional MRI, and positron emission tomography have provided higher resolution depictions of structural and functional connectivity between regions of interest. Applying these imaging modalities to DBS has increased understanding of the mechanism of action of DBS from the single structure to network level, allowed for new DBS targets to be discovered, and allowed for individualized DBS targeting for psychiatric indications. CONCLUSIONS: Advanced neuroimaging techniques may be especially important to guide personalized DBS targeting in psychiatric disorders such as treatment-resistant depression and obsessive-compulsive disorder where symptom profiles and underlying disordered circuitry are more heterogeneous. These articles suggest that advanced imaging can help to further individualize and optimize DBS, a promising next step in improving its efficacy.

Caudate stimulation enhances learning.

Neuromodulation is a promising treatment modality for disorders of learning and memory, offering the possibility of precise alteration of disordered neural circuits. Studies to date have failed to identify an optimal target and stimulation paradigm. Six epilepsy patients with depth electrodes implanted for seizure localization participated in our study. We recorded local field potentials from implanted electrodes while subjects participated in an associative learning task requiring them to learn an association between presented images and a button press. Three subjects participated in stimulation sessions during which caudate or putamen stimulation was delivered for some images during feedback after correct responses. Caudate stimulation enhanced learning. Both caudate and dorsolateral prefrontal cortex demonstrated a beta power increase during the feedback period of the learning task that was greater following correct than incorrect trials. In dorsolateral prefrontal cortex, this difference increased with learning and persisted beyond the end of the feedback period. Caudate stimulation was associated with increased dorsolateral prefrontal cortex beta power following feedback. These findings suggest that temporally specific caudate stimulation is a promising neuromodulation strategy to improve learning in disorders of learning and memory.

Vagus Nerve Stimulation versus Responsive Neurostimulator System in Patients with Temporal Lobe Epilepsy.

INTRODUCTION: Patients with medically refractory temporal lobe epilepsy (TLE) are candidates for neuromodulation procedures. While vagus nerve stimulation (VNS) was historically the procedure of choice for this condition, the responsive neurostimulation system (RNS) has come into favor for its more targeted approach. While both VNS and RNS have been reported as efficacious treatments for TLE, the outcomes of these 2 procedures have not been directly compared. This study aims to compare outcomes following VNS versus RNS for TLE. METHODS: We retrospectively reviewed the records of all patients with TLE who underwent VNS or RNS placement at our institution from 2003 to 2018. The primary outcome was change in seizure frequency. Other outcomes included Engel score, change in anti-epileptic medications, and complications. RESULTS: Twenty-three patients met inclusion criteria; 11 underwent VNS and 12 underwent RNS. At baseline, the 2 groups were statistically similar regarding age at surgery, epilepsy duration, and preoperative seizure frequency. At last follow-up, both groups displayed reduced seizure frequency (mean reduction of 46.3% for the VNS group and 58.1% for the RNS group, p = 0.49). Responder rate, Engel score, and change in medications were statistically similar between groups. Compared to 0.0% of the VNS group, 13.3% of the RNS group experienced infection requiring re-operation. CONCLUSION: Despite their different mechanisms, VNS and RNS resulted in similar response rates for patients with TLE. We suggest that VNS should not be excluded as a treatment for patients with medically refractory TLE who are not candidates for resective or ablative procedures.

Subthalamic Nucleus Deep Brain Stimulation Alters Prefrontal Correlates of Emotion Induction.

OBJECTIVES: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in advanced Parkinson's disease. STN DBS may also affect emotion, possibly by impacting a parallel limbic cortico-striatal circuit. The objective of this study was to investigate changes in prefrontal cortical activity related to DBS during an emotion induction task. MATERIALS AND METHODS: We used near infrared spectroscopy to monitor prefrontal cortex hemodynamic changes during an emotion induction task. Seven DBS patients were tested sequentially in the stimulation-on and stimulation-off states while on dopaminergic medication. Patients watched a series of positive, negative, and neutral videos. The general linear model was used to compare prefrontal oxygenated hemoglobin concentration between DBS states. RESULTS: Deep brain stimulation was correlated with prefrontal oxygenated hemoglobin changes relative to the stimulation off state in response to both positive and negative videos. These changes were specific to emotional stimuli and were not seen during neutral stimuli. CONCLUSIONS: These results suggest that STN stimulation influences the prefrontal cortical representation of positive and negative emotion induction.

Neuromodulation for restoring memory.

Disorders of learning and memory have a large social and economic impact in today's society. Unfortunately, existing medical treatments have shown limited clinical efficacy or potential for modification of the disease course. Deep brain stimulation is a successful treatment for movement disorders and has shown promise in a variety of other diseases including psychiatric disorders. The authors review the potential of neuromodulation for the treatment of disorders of learning and memory. They briefly discuss learning circuitry and its involvement in Alzheimer disease and traumatic brain injury. They then review the literature supporting various targets for neuromodulation to improve memory in animals and humans. Multiple targets including entorhinal cortex, fornix, nucleus basalis of Meynert, basal ganglia, and pedunculopontine nucleus have shown a promising potential for improving dysfunctional memory by mechanisms such as altering firing patterns in neuronal networks underlying memory and increasing synaptic plasticity and neurogenesis. Significant work remains to be done to translate these findings into durable clinical therapies.

Anterior Temporal Lobectomy for Refractory Status Epilepticus in Herpes Simplex Encephalitis.

BACKGROUND: Herpes simplex virus (HSV) is a common cause of viral encephalitis that can lead to refractory seizures. The primary treatment of HSV encephalitis is with acyclovir; however, surgery sometimes plays a role in obtaining tissue diagnosis or decompression in cases with severe mass effect. We report a unique case in which anterior temporal lobectomy was successfully used to treat refractory status epilepticus in HSV encephalitis. METHODS: Case report and review of the literature. RESULTS: We report a case of a 60-year-old man with HSV encephalitis, who presented with seizures originating from the right temporal lobe refractory to maximal medical management. Right anterior temporal lobectomy was performed for the purpose of treatment of refractory status epilepticus and obtaining tissue diagnosis, with ultimate resolution of seizures and excellent functional outcome. CONCLUSIONS: We suggest that anterior temporal lobectomy should be considered in cases of HSV encephalitis with refractory status epilepticus with clear unilateral origin.

The association between motor and non-motor symptoms in essential tremor patients being evaluated for deep brain stimulation surgery.

BACKGROUND: Non-motor symptoms, including depression and cognitive impairment, are common in essential tremor (ET), but associations between these symptoms and tremor are poorly understood. METHODS: A retrospective, single-institution, cohort study evaluated 140 patients with ET undergoing evaluation for deep brain stimulation (DBS) surgery. The Fahn-Tolosa-Marin (FTM) or Washington Heights-Inwood Genetic Study of ET (WHIGET) scale was used to grade tremor. Tremor scores were divided into quartiles. Patients underwent clinical neuropsychological evaluations that included a comprehensive cognitive test battery and Beck Depression Inventory-II (BDI-II). Subgroup analysis was performed with groups who met criteria for depression (BDI-II > 14) or overall cognitive impairment (<9th percentile on at least two dissimilar cognitive tests). Independent samples t-tests were used for continuous variables and chi square tests for categorical variables. Univariable and multivariable regressions were used to determine relationships between tremor and non-motor scores. RESULTS: Tremor quartile was correlated with language domain performance (p = 0.044) but not depression scores. FTM score was associated with BDI-II (ß = 0.940, p = 0.010), language (ß = -0.936, p = 0.012), and visuospatial domain (ß = -0.836, p = 0.025) scores, such that worse tremor was associated with more depression and worse language and visuospatial function. WHIGET score was not associated with any neuropsychological scores on multivariable regression. CONCLUSION: FTM score was associated with language, visuospatial, and mood symptoms, suggesting a relationship between the severity of these symptom types. Different tremor scores capture different motor symptoms and relationships with nonmotor symptoms.

Brain-wide human oscillatory local field potential activity during visual working memory.

Oscillatory activity in the local field potential (LFP) is thought to be a marker of cognitive processes. To understand how it differentiates tasks and brain areas in humans, we recorded LFPs in 15 adults with intracranial depth electrodes, as they performed visual-spatial and shape working memory tasks. Stimulus appearance produced widespread, broad-band activation, including in occipital, parietal, temporal, insular, and prefrontal cortex, and the amygdala and hippocampus. Occipital cortex was characterized by most elevated power in the high-gamma (100-150 Hz) range during the visual stimulus presentation. The most consistent feature of the delay period was a systematic pattern of modulation in the beta frequency (16-40 Hz), which included a decrease in power of variable timing across areas, and rebound during the delay period. These results reveal the widespread nature of oscillatory activity across a broad brain network and region-specific signatures of oscillatory processes associated with visual working memory.

Electrode position and cognitive outcome following deep brain stimulation surgery.

OBJECTIVE: Subthalamic nucleus (STN) and globus pallidus internus (GPI) deep brain stimulation (DBS) effectively treat motor symptoms in Parkinson's disease (PD) but may be associated with cognitive and psychiatric changes in some patients. Evaluation of changes in cognitive and psychiatric symptoms following DBS is complicated by changes in these symptoms that occur as part of the natural disease course. The aim of this study was to evaluate whether electrode position was associated with changes in neurocognitive symptoms in patients who underwent STN and GPI DBS. METHODS: A single-institution retrospective cohort study was conducted on patients with PD who underwent DBS from 2008 to 2019. Cognitive and psychiatric outcomes included Beck Depression Inventory II (BDI-II) score, presence of impulsive-compulsive behavior (ICB), Mini-Mental State Examination (MMSE) score, and overall cognitive status grade determined by comprehensive neuropsychology testing (normal, mild impairment, moderate impairment, and dementia). Pre- and postoperative comparisons were performed using a Wilcoxon signed-rank test or paired t-test. Patients with and without cognitive decline were compared using a Mann-Whitney U-test or unpaired t-test. A chi-square test was used for categorical comparisons. RESULTS: One hundred thirty patients were included (mean age 62.5 ± 7.9 years). At a mean postoperative follow-up from DBS of 13.0 ± 12.7 (range 6-66) months, there was an improvement in ICB (26.3% preoperatively vs 15.0% postoperatively, p = 0.017), but a decline in MMSE score (28.6 ± 1.6 vs 27.6 ± 2.0, p < 0.001) and overall cognitive status (normal: 66.2% vs 39.2%; mild: 12.3% vs 17.7%; moderate: 21.5% vs 33.1%; dementia: 0.0% vs 10.0%; p < 0.001). Patients undergoing STN DBS had a worse decline in overall cognitive status than patients who underwent GPI DBS (p = 0.006). Postoperative cognitive decline was associated with a more medial electrode position only for patients who underwent STN DBS. CONCLUSIONS: Cognitive change was observed in some patients with PD who underwent both GPI and STN DBS, likely due partly to underlying disease progression. Compared with GPI DBS, STN DBS was associated with a greater likelihood of cognitive decline. In STN but not GPI DBS, cognitive decline was associated with medialized electrode position, suggesting modulation of nonmotor STN divisions may contribute to cognitive changes following STN DBS.

Reward Circuit Local Field Potential Modulations Precede Risk Taking.

Risk taking behavior is a symptom of multiple neuropsychiatric disorders and often lacks effective treatments. Reward circuitry regions including the amygdala, orbitofrontal cortex, insula, and anterior cingulate have been implicated in risk-taking by neuroimaging studies. Electrophysiological activity associated with risk taking in these regions is not well understood in humans. Further characterizing the neural signalling that underlies risk-taking may provide therapeutic insight into disorders associated with risk-taking. Eleven patients with pharmacoresistant epilepsy who underwent stereotactic electroencephalography with electrodes in the amygdala, orbitofrontal cortex, insula, and/or anterior cingulate participated. Patients participated in a gambling task where they wagered on a visible playing card being higher than a hidden card, betting $5 or $20 on this outcome, while local field potentials were recorded from implanted electrodes. We used cluster-based permutation testing to identify reward prediction error signals by comparing oscillatory power following unexpected and expected rewards. We also used cluster-based permutation testing to compare power preceding high and low bets in high-risk (<50% chance of winning) trials and two-way ANOVA with bet and risk level to identify signals associated with risky, risk averse, and optimized decisions. We used linear mixed effects models to evaluate the relationship between reward prediction error and risky decision signals across trials, and a linear regression model for associations between risky decision signal power and Barratt Impulsiveness Scale scores for each patient. Reward prediction error signals were identified in the amygdala (p=0.0066), anterior cingulate (p=0.0092), and orbitofrontal cortex (p=6.0E-4, p=4.0E-4). Risky decisions were predicted by increased oscillatory power in high-gamma frequency range during card presentation in the orbitofrontal cortex (p=0.0022), and by increased power following bet cue presentation across the theta-to-beta range in the orbitofrontal cortex ( p =0.0022), high-gamma in the anterior cingulate ( p =0.0004), and high-gamma in the insula ( p =0.0014). Risk averse decisions were predicted by decreased orbitofrontal cortex gamma power ( p =2.0E-4). Optimized decisions that maximized earnings were preceded by decreases within the theta to beta range in orbitofrontal cortex ( p =2.0E-4), broad frequencies in amygdala ( p =2.0E-4), and theta to low-gamma in insula ( p =4.0E-4). Insula risky decision power was associated with orbitofrontal cortex high-gamma reward prediction error signal ( p =0.0048) and with patient impulsivity ( p =0.00478). Our findings identify and help characterize reward circuitry activity predictive of risk-taking in humans. These findings may serve as potential biomarkers to inform the development of novel treatment strategies such as closed loop neuromodulation for disorders of risk taking.

Benefits of stereotactic radiosurgical anterior capsulotomy for obsessive-compulsive disorder: a meta-analysis.

OBJECTIVE: Anterior capsulotomy (AC) is a therapeutic option for patients with severe, treatment-resistant obsessive-compulsive disorder (OCD). The procedure can be performed via multiple techniques, with stereotactic radiosurgery (SRS) gaining popularity because of its minimally invasive nature. The risk-benefit profile of AC performed specifically with SRS has not been well characterized. Therefore, the primary objective of this study was to characterize outcomes following stereotactic radiosurgical AC in OCD patients. METHODS: Studies assessing mean Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores before and after stereotactic radiosurgical AC for OCD were included in this analysis. Inverse-variance fixed-effect modeling was used for pooling, and random-effects estimate of the ratio of means and standard mean differences were calculated at 6 months, 12 months, and the last follow-up for Y-BOCS scores, as well as the last follow-up for the Beck Depression Inventory (BDI)/BDI-II scores. A generalized linear mixed model was used to generate fixed- and random-effects models for categorical outcomes. Univariate random-effects meta-regression was used to evaluate associations between postoperative Y-BOCS scores and study covariates. Adverse events were summed across studies. Publication bias was assessed with Begg's test. RESULTS: Eleven studies with 180 patients were eligible for inclusion. The mean Y-BOCS score decreased from 33.28 to 17.45 at the last-follow up (p < 0.001). Sixty percent of patients were classified as responders and 10% as partial responders, 18% experienced remission, and 4% had worsened Y-BOCS scores. The degree of improvement in the Y-BOCS score correlated with time since surgery (p = 0.046). In the random-effects model, the mean BDI at the last follow-up was not significantly different from that preoperatively. However, in an analysis performed with available paired pre- and postoperative BDI/BDI-II scores, there was significant improvement in the BDI/BDI-II scores postoperatively. Adverse events numbered 235, with headaches, weight change, mood changes, worsened depression/anxiety, and apathy occurring most commonly. CONCLUSIONS: Stereotactic radiosurgical AC is an effective technique for treating OCD. Its efficacy is similar to that of AC performed via other lesioning techniques.

Improving Visual Working Memory with Cholinergic Deep Brain Stimulation.

Acetylcholine is a critical modulatory neurotransmitter for cognitive function. Cholinergic drugs improve cognitive performance and enhance neuronal activity in the sensory and association cortices. An alternative means of improving cognitive function is through the use of deep brain stimulation. Prior animal studies have demonstrated that stimulation of the nucleus basalis of Meynert through DBS improves cognitive performance on a visual working memory task to the same degree as cholinesterase inhibitors. Additionally, unlike current pharmacological treatments for neurocognitive disorders, DBS does not lose efficacy over time and adverse effects are rare. These findings suggest that DBS may be a promising alternative for treating cognitive impairments in neurodegenerative disorders such as Alzheimer's disease. Thus, further research and human trials should be considered to assess the potential of DBS as a therapeutic treatment for these disorders.