Probabilistic Mapping of Deep Brain Stimulation: Insights from 15 Years of Therapy.

Deep brain stimulation (DBS) depends on precise delivery of electrical current to target tissues. However, the specific brain structures responsible for best outcome are still debated. We applied probabilistic stimulation mapping to a retrospective, multidisorder DBS dataset assembled over 15 years at our institution (ntotal = 482 patients; nParkinson disease = 303; ndystonia = 64; ntremor = 39; ntreatment-resistant depression/anorexia nervosa = 76) to identify the neuroanatomical substrates of optimal clinical response. Using high-resolution structural magnetic resonance imaging and activation volume modeling, probabilistic stimulation maps (PSMs) that delineated areas of above-mean and below-mean response for each patient cohort were generated and defined in terms of their relationships with surrounding anatomical structures. Our results show that overlap between PSMs and individual patients' activation volumes can serve as a guide to predict clinical outcomes, but that this is not the sole determinant of response. In the future, individualized models that incorporate advancements in mapping techniques with patient-specific clinical variables will likely contribute to the optimization of DBS target selection and improved outcomes for patients. ANN NEUROL 2021;89:426-443.

Ipsilateral and axial tremor response to focused ultrasound thalamotomy for essential tremor: clinical outcomes and probabilistic mapping.

BACKGROUND: MR-guided focused ultrasound (MRgFUS) thalamotomy has been shown to be a safe and effective treatment for essential tremor (ET). OBJECTIVE: To investigate the effects of MRgFUS in patients with ET with an emphasis on ipsilateral-hand and axial tremor subscores. METHODS: Tremor scores and adverse effects of 100 patients treated between 2012 and 2018 were assessed at 1 week, 3, 12, and 24 months. A subgroup analysis of ipsilateral-hand tremor responders (defined as patients with ≥30% improvement at any time point) and non-responders was performed. Correlations and predictive factors for improvement were analysed. Weighted probabilistic maps of improvement were generated. RESULTS: Significant improvement in axial, contralateral-hand and total tremor scores was observed at all study visits from baseline (p<0.0001). There was no significant improvement in ipsilateral subscores. A subset of patients (n=20) exhibited group-level ipsilateral-hand improvement that remained significant through all follow-ups (p<0.001). Multivariate regression analysis revealed that higher baseline scores predict better improvement in ipsilateral-hand and axial tremor. Probabilistic maps demonstrated that the lesion hotspot for axial improvement was situated more medially than that for contralateral improvement. CONCLUSION: MRgFUS significantly improved axial, contralateral-hand and total tremor scores. In a subset of patients, a consistent group-level treatment effect was observed for ipsilateral-hand tremor. While ipsilateral improvement seemed to be less directly related to lesion location, a spatial relationship between lesion location and axial and contralateral improvement was observed that proved consistent with the somatotopic organisation of the ventral intermediate nucleus. TRIAL REGISTRATION NUMBERS: NCT01932463, NCT01827904, and NCT02252380.

Deep brain stimulation of the brainstem.

Deep brain stimulation (DBS) of the subthalamic nucleus, pallidum, and thalamus is an established therapy for various movement disorders. Limbic targets have also been increasingly explored for their application to neuropsychiatric and cognitive disorders. The brainstem constitutes another DBS substrate, although the existing literature on the indications for and the effects of brainstem stimulation remains comparatively sparse. The objective of this review was to provide a comprehensive overview of the pertinent anatomy, indications, and reported stimulation-induced acute and long-term effects of existing white and grey matter brainstem DBS targets. We systematically searched the published literature, reviewing clinical trial articles pertaining to DBS brainstem targets. Overall, 164 studies describing brainstem DBS were identified. These studies encompassed 10 discrete structures: periaqueductal/periventricular grey (n = 63), pedunculopontine nucleus (n = 48), ventral tegmental area (n = 22), substantia nigra (n = 9), mesencephalic reticular formation (n = 7), medial forebrain bundle (n = 8), superior cerebellar peduncles (n = 3), red nucleus (n = 3), parabrachial complex (n = 2), and locus coeruleus (n = 1). Indications for brainstem DBS varied widely and included central neuropathic pain, axial symptoms of movement disorders, headache, depression, and vegetative state. The most promising results for brainstem DBS have come from targeting the pedunculopontine nucleus for relief of axial motor deficits, periaqueductal/periventricular grey for the management of central neuropathic pain, and ventral tegmental area for treatment of cluster headaches. Brainstem DBS has also acutely elicited numerous motor, limbic, and autonomic effects. Further work involving larger, controlled trials is necessary to better establish the therapeutic potential of DBS in this complex area.

Microelectrode Recording and Radiofrequency Thalamotomy following Focused Ultrasound Thalamotomy.

Magnetic resonance imaging-guided focused ultrasound (MRgFUS) is a novel method for stereotactic brain lesioning and has primarily been applied for thalamotomies to treat essential tremor (ET). The electrophysiological properties of previously MRgFUS-sonicated thalamic neurons have not yet been described. We report on an ET patient who underwent an MRgFUS thalamotomy but experienced tremor recurrence. We expanded the MRgFUS-induced thalamic cavity using radiofrequency (RF), with good effect on the tremor but transient sensorimotor deficits and permanent ataxia. This is the first report of a patient undergoing RF thalamotomy after an unsuccessful MRgFUS thalamotomy. As we used microelectrode recording to guide the RF thalamotomy, we could also study for the first time the electrophysiological properties of previously sonicated thalamic neurons bordering the MRgFUS-induced cavity. These neurons displayed electrophysiological characteristics identical to those recorded from nonsonicated thalamic cells in ET patients. Hence, our findings support the widespread assumption that sonication below the necrotic threshold does not permanently alter neuronal function.

Neuronal Activity and Synaptic Plasticity in a Reimplanted STN-DBS Patient with Parkinson's Disease: Recordings from Two Surgeries.

The authors report the case of an elderly male in his 60s who, after 5 months of efficacious treatment with chronic deep brain stimulation of the subthalamic nucleus (STN-DBS), developed a hardware-related erosion necessitating removal of the complete DBS system. One and a half years following the first implantation, a new STN-DBS system was implanted along an immediately adjacent trajectory, and reproduction of clinical efficacy was reported. Additionally, 2 microstimulation protocols were compared between the 2 surgeries, i.e., one to assess the stimulation frequency response of STN neurons and another to assess inhibitory synaptic plasticity in the substantia nigra pars reticulata (SNr). The spontaneous neuronal firing rates of STN neurons in each hemisphere were also compared between the 2 surgeries. The results suggest that the frequency-sensitivity of STN neurons may have been reduced (i.e., more resistant to neuronal suppression), while the spontaneous baseline firing rates of STN neurons and the plasticity measured in the SNr remained unchanged (2 factors that may be indicative of neurodegenerative processes).

Structural mapping with fiber tractography of the human cuneate fasciculus at microscopic resolution in cervical region.

Human spinal white matter tract anatomy has been mapped using post mortem histological information with the help of molecular tracing studies in animal models. This study used 7 Tesla diffusion MR tractography on a human cadaver that was harvested 24 hours post mortem to evaluate cuneate fasciculus anatomy in cervical spinal cord. Based on this method, for the first time much more nuanced tractographic anatomy was used to investigate possible new routes for cuneate fasciculus in the posterior and lateral funiculus. Additionally, current molecular tracing studies were reviewed, and confirmatory data was presented along with our radiological results. Both studies confirm that upon entry to the spinal cord, upper cervical level tracts (C1-2-3) travel inside lateral funiculus and lower level tracts travel medially inside the posterior funiculus after entry at posterolateral sulcus which is different than traditional knowledge of having cuneate fasciculus tracts concentrated in the lateral part of posterior funiculus.

Modulation of inhibitory plasticity in basal ganglia output nuclei of patients with Parkinson's disease.

Deep brain stimulation of certain target structures within the basal ganglia is an effective therapy for the management of the motor symptoms of Parkinson's disease. However, its mechanisms, as well as the pathophysiology of Parkinson's disease, are varied and complex. The classical model of Parkinson's disease states that symptoms may arise as a result of increased neuronal activity in the basal ganglia output nuclei due to downregulated GABAergic striato-nigral/-pallidal projections. We sought to investigate the stimulation and levodopa induced effects on inhibitory synaptic plasticity in these basal ganglia output nuclei, and to determine the clinical relevance of altered plasticity with respect to patients' symptoms. Two closely spaced microelectrodes were advanced into the substantia nigra pars reticulata (potential novel therapeutic target for axial motor symptoms) or globus pallidus internus (conventional therapeutic target) in each of 28 Parkinson's disease patients undergoing subthalamic or pallidal deep brain stimulation surgery. Sets of 1 Hz test-pulses were delivered at different cathodal pulse widths (25, 50, 100, 150, 250 µs) in randomized order, before and after a train of continuous high frequency stimulation at 100 Hz. Increasing the pulse width led to progressive increases in both the amplitudes of extracellular focally evoked inhibitory field potentials and durations of neuronal silent periods. Both of these effects were augmented after a train of continuous high frequency stimulation. Additionally, reductions in the baseline neuronal firing rate persisted beyond 1 min after high frequency stimulation. We found greater enhancements of plasticity in the globus pallidus internus compared to the substantia nigra pars reticulata, and that intraoperative levodopa administration had a potent effect on the enhancement of nigral plasticity. We also found that lower levels of nigral plasticity were associated with higher severity motor symptoms. The findings of this study demonstrate that the efficacy of inhibitory synaptic transmission may be involved in the pathophysiology of Parkinson's disease, and furthermore may have implications for the development of novel stimulation protocols, and advancement of DBS technologies.

Functional MRI Safety and Artifacts during Deep Brain Stimulation: Experience in 102 Patients.

BackgroundWith growing numbers of patients receiving deep brain stimulation (DBS), radiologists are encountering these neuromodulation devices at an increasing rate. Current MRI safety guidelines, however, limit MRI access in these patients.PurposeTo describe an MRI (1.5 T and 3 T) experience and safety profile in a large cohort of participants with active DBS systems and characterize the hardware-related artifacts on images from functional MRI.Materials and MethodsIn this prospective study, study participants receiving active DBS underwent 1.5- or 3-T MRI (T1-weighted imaging and gradient-recalled echo [GRE]-echo-planar imaging [EPI]) between June 2017 and October 2018. Short- and long-term adverse events were tracked. The authors quantified DBS hardware-related artifacts on images from GRE-EPI (functional MRI) at the cranial coil wire and electrode contacts. Segmented artifacts were then transformed into standard space to define the brain areas affected by signal loss. Two-sample t tests were used to assess the difference in artifact size between 1.5- and 3-T MRI.ResultsA total of 102 participants (mean age ± standard deviation, 60 years ± 11; 65 men) were evaluated. No MRI-related short- and long-term adverse events or acute changes were observed. DBS artifacts were most prominent near the electrode contacts and over the frontoparietal cortical area where the redundancy of the extension wire is placed subcutaneously. The mean electrode contact artifact diameter was 9.3 mm ± 1.6, and 1.9% ± 0.8 of the brain was obscured by the coil artifact. The coil artifacts were larger at 3 T than at 1.5 T, obscuring 2.1% ± 0.7 and 1.4% ± 0.7 of intracranial volume, respectively (P < .001). The superficial frontoparietal cortex and deep structures neighboring the electrode contacts were most commonly obscured.ConclusionWith a priori local safety testing, patients receiving deep brain stimulation may safely undergo 1.5- and 3-T MRI. Deep brain stimulation hardware-related artifacts only affect a small proportion of the brain.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Martin in this issue.

Neuroimaging Technological Advancements for Targeting in Functional Neurosurgery.

PURPOSE OF REVIEW: Ablations and particularly deep brain stimulation (DBS) of a variety of CNS targets are established therapeutic tools for movement disorders. Accurate targeting of the intended structure is crucial for optimal clinical outcomes. However, most targets used in functional neurosurgery are sub-optimally visualized on routine MRI. This article reviews recent neuroimaging advancements for targeting in movement disorders. RECENT FINDINGS: Dedicated MRI sequences can often visualize to some degree anatomical structures commonly targeted during DBS surgery, including at 1.5-T field strengths. Due to recent technological advancements, MR images using ultra-high magnetic field strengths and new acquisition parameters allow for markedly improved visualization of common movement disorder targets. In addition, novel neuroimaging techniques have enabled group-level analysis of DBS patients and delineation of areas associated with clinical benefits. These areas might diverge from the conventionally targeted nuclei and may instead correspond to white matter tracts or hubs of functional networks. Neuroimaging advancements have enabled improved direct visualization-based targeting as well as optimization and adjustment of conventionally targeted structures.

The Incidence of Spinal Cord Injury in Implantation of Percutaneous and Paddle Electrodes for Spinal Cord Stimulation.

OBJECTIVE: Spinal cord stimulation (SCS) has been proven effective for multiple chronic pain syndromes. Over the past 40 years of use, the complication rates of SCS have been well defined in the literature; however, the incidence of one of the most devastating complications, spinal cord injury (SCI), remains largely unknown. The goal of the study was to quantify the incidence of SCI in both percutaneous and paddle electrode implantation. METHODS: We conducted a retrospective review of the Thomson Reuter's MarketScan database of all patients that underwent percutaneous or paddle SCS implantation from 2000 to 2009. The main outcome measures of the study were the incidence of SCI and spinal hematoma within 30 days following operation. RESULTS: Overall 8326 patients met inclusion criteria for the study (percutaneous: 5458 vs. paddle: 2868). The overall incidence of SCI was 177 (2.13%) (percutaneous: 128 (2.35%) vs. paddle: 49 (1.71%), p = 0.0556). The overall incidence of spinal hematoma was 59 (0.71%) (percutaneous: 41 (0.75%) vs. paddle: 18 (0.63%), p = 0.5230). CONCLUSION: Our study shows that the overall incidence of SCI in SCS is low (2.13%), supporting that SCS is a safe procedure. No significant difference was found in the rates of SCI or spinal hematoma between the percutaneous and paddle groups. Further studies are needed to characterize the mechanisms of SCI in SCS and long-term outcomes in these patients.

Effect of overground training augmented by mental practice on gait velocity in chronic, incomplete spinal cord injury.

OBJECTIVE: To compare the efficacy of a regimen combining mental practice (MP) with overground training (OT) with the efficacy of a regimen consisting of OT only on gait velocity and lower extremity motor outcomes in individuals with chronic (>12mo postinjury), incomplete spinal cord injury (SCI). DESIGN: Randomized, controlled, single-blinded study. SETTING: Outpatient rehabilitation laboratories. PARTICIPANTS: Subjects with chronic, incomplete SCI (N=18). INTERVENTIONS: Subjects were randomly assigned to receive (1) OT only, occurring 3d/wk for 8 weeks; or (2) OT augmented by MP (MP + OT), during which randomly assigned subjects listened to an MP audio recording directly after OT sessions. MAIN OUTCOME MEASURES: Subjects were administered a test of gait velocity as well as the Tinetti Performance Oriented Mobility Assessment, Spinal Cord Injury Independence Measure, and Satisfaction With Life Scale on 2 occasions before intervention, 1 week after intervention, and 12 weeks after intervention. RESULTS: A significant increase in gait velocity was exhibited across subjects at both 1 week posttherapy (P=.005) and at 12 weeks posttherapy (P=.006). However, no differences were seen in intervention response at either 1 or 12 weeks postintervention among subjects in the MP + OT group versus the OT-only group. CONCLUSIONS: OT was associated with significant gains in gait velocity, and these gains were not augmented by further addition of MP.

Clinical Utility of Near-Infrared Device in Detecting Traumatic Intracranial Hemorrhage: A Pilot Study Toward Application as an Emergent Diagnostic Modality in a Low-Resource Setting.

Limited computed tomography (CT) availability in low- and middle-income countries frequently impedes life-saving neurosurgical decompression for traumatic brain injury. A reliable, accessible, cost-effective solution is necessary to detect and localize bleeds. We report the largest study to date using a near-infrared device (NIRD) to detect traumatic intracranial bleeds. Patients with confirmed or suspected head trauma who received a head CT scan were included. Within 30 min of the initial head CT scan, a blinded examiner scanned each patient's cranium with a NIRD, interrogating bilaterally the frontal, parietal, temporal, and occipital quadrants Sensitivity, specificity, accuracy, and precision were investigated. We recruited 500 consecutive patients; 104 patients had intracranial bleeding. For all patients with CT-proven bleeds, irrespective of size, initial NIRD scans localized the bleed to the appropriate quadrant with a sensitivity of 86% and specificity of 96% compared with CT. For extra-axial bleeds >3.5mL, sensitivity and specificity were 94% and 96%, respectively. For longitudinal serial rescans with the NIRD, sensitivity was 89% (< 4 days from injury: sensitivity: 99%), and specificity was 96%. For all patients who required craniectomy or craniotomy, the device demonstrated 100% sensitivity. NIRD is highly sensitive, specific, and reproducible over time in diagnosing intracranial bleeds. NIRD may inform neurosurgical decision making in settings where CT scanning is unavailable or impractical.

A Nationwide Analysis of Aneurysmal Subarachnoid Hemorrhage Mortality, Complications, and Health Economics in the USA.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological condition. Endovascular coiling or surgical clipping have equivocal success rates, but relatively little is known regarding the health economics and complications of these procedures at the population level. We aimed to analyze the complication profiles and healthcare resource utilization (HRCU) associated with the treatment of aSAH in the USA. We performed a retrospective analysis utilizing the IBM MarketScan database between 2008 and 2015. Primary outcomes included economic analysis stratified by post-operative complication; determination of the effect of several factors on total cost by multivariable regression; and analysis of the incidence, timing, and associated HCRU of aSAH-related post-operative complications. Of the 2374 patients meeting inclusion criteria for economic analysis, 1783 (75.1%) patients had at least one of the ten complications. The most common complications included hydrocephalus (43.8%), transient cerebral ischemia (including vasospasm) (30.6%), ischemic stroke (29.1%), syndrome of inappropriate antidiuretic hormone (SIADH)/hyposmolarity/hyponatremia (22.1%), and seizures (14.9%). Patients who experienced complications had higher median 90-day total costs [$161,127 (Q1 to Q3, $101,411 to $257,662)] than those who did not [$97,376 (Q1 to Q3, $55,692 to $147,447)]. Length of stay was longest for those with pulmonary embolism and pneumonia (27 days) and shortest for those with SIADH/hyposmolarity/hyponatremia (16 days). Brain compression/herniation had the highest mortality rate (19.5%). In total, 14.6% of all patients experienced a readmission within 30 days. In conclusion, patients with aSAH have high post-operative complication rates and costs. Development of novel interventions to reduce complications and improve outcomes is crucial.

Dysgeusia induced and resolved by focused ultrasound thalamotomy: case report.

Dysgeusia, or distorted taste, has recently been acknowledged as a complication of thalamic ablation or thalamic deep brain stimulation as a treatment of tremor. In a unique patient, left-sided MR-guided focused ultrasound thalamotomy improved right-sided essential tremor but also induced severe dysgeusia. Although dysgeusia persisted and caused substantial weight loss, tremor slowly relapsed. Therefore, 19 months after the first procedure, the patient underwent a second focused ultrasound thalamotomy procedure, which again improved tremor but also completely resolved the dysgeusia. On the basis of normative and patient-specific whole-brain tractography, the authors determined the relationship between the thalamotomy lesions and the medial border of the medial lemniscus-a surrogate for the solitariothalamic gustatory fibers-after the first and second focused ultrasound thalamotomy procedures. Both tractography methods suggested partial and complete disruption of the solitariothalamic gustatory fibers after the first and second thalamotomy procedures, respectively. The tractography findings in this unique patient demonstrate that incomplete and complete disruption of a neural pathway can induce and resolve symptoms, respectively, and serve as the rationale for ablative procedures for neurological and psychiatric disorders.

Predicting the Individual Treatment Effect of Neurosurgery for Patients with Traumatic Brain Injury in the Low-Resource Setting: A Machine Learning Approach in Uganda.

Traumatic brain injury (TBI) disproportionately affects low- and middle-income countries (LMICs). In these low-resource settings, effective triage of patients with TBI-including the decision of whether or not to perform neurosurgery-is critical in optimizing patient outcomes and healthcare resource utilization. Machine learning may allow for effective predictions of patient outcomes both with and without surgery. Data from patients with TBI was collected prospectively at Mulago National Referral Hospital in Kampala, Uganda, from 2016 to 2019. One linear and six non-linear machine learning models were designed to predict good versus poor outcome near hospital discharge and internally validated using nested five-fold cross-validation. The 13 predictors included clinical variables easily acquired on admission and whether or not the patient received surgery. Using an elastic-net regularized logistic regression model (GLMnet), with predictions calibrated using Platt scaling, the probability of poor outcome was calculated for each patient both with and without surgery (with the difference quantifying the "individual treatment effect," ITE). Relative ITE represents the percent reduction in chance of poor outcome, equaling this ITE divided by the probability of poor outcome with no surgery. Ultimately, 1766 patients were included. Areas under the receiver operating characteristic curve (AUROCs) ranged from 83.1% (single C5.0 ruleset) to 88.5% (random forest), with the GLMnet at 87.5%. The two variables promoting good outcomes in the GLMnet model were high Glasgow Coma Scale score and receiving surgery. For the subgroup not receiving surgery, the median relative ITE was 42.9% (interquartile range [IQR], 32.7% to 53.5%); similarly, in those receiving surgery, it was 43.2% (IQR, 32.9% to 54.3%). We provide the first machine learning-based model to predict TBI outcomes with and without surgery in LMICs, thus enabling more effective surgical decision making in the resource-limited setting. Predicted ITE similarity between surgical and non-surgical groups suggests that, currently, patients are not being chosen optimally for neurosurgical intervention. Our clinical decision aid has the potential to improve outcomes.

Impact of Mesial Temporal Lobe Resection on Brain Structure in Medically Refractory Epilepsy.

OBJECTIVE: Surgical resection can decrease seizure frequency in medically intractable temporal lobe epilepsy. However, the functional and structural consequences of this intervention on brain circuitry are poorly understood. We investigated structural changes that occur in brain circuits after mesial temporal lobe resection for refractory epilepsy. Specifically, we used neuroimaging techniques to evaluate changes in 1) contralesional hippocampal and bilateral mammillary body volume and 2) brain-wide cortical thickness. METHODS: Serial T1-weighted brain magnetic resonance images were acquired before and after surgery (1.6 ± 0.5 year interval) in 21 patients with temporal lobe epilepsy (9 women, 12 men; mean age, 39.4 ± 11.5 years) who had undergone unilateral temporal lobe resection (14 anterior temporal lobectomy; 7 selective amygdalohippocampectomy). Blinded manual segmentation of the unresected hippocampal formation and bilateral mammillary bodies was performed using the Pruessner and Copenhaver protocols, respectively. Brain-wide cortical thickness estimates were computed using the CIVET pipeline. RESULTS: Surgical resection was associated with a 5% reduction in contralesional hippocampal volume (P < 0.01) and a 9.5% reduction in mammillary body volume (P = 0.03). In addition, significant changes in cortical thickness were observed in contralesional anterior and middle cingulate gyrus and insula (Pfalse discovery rate < 0.01) as well as in other temporal, frontal, and occipital regions (Pfalse discovery rate < 0.05). Postoperative verbal memory function was significantly associated with cortical thickness change in contralesional inferior temporal gyrus (R2 = 0.39; P = 0.03). CONCLUSIONS: These results indicate that mesial temporal lobe resection is associated with both volume loss in spared Papez circuitry and changes in cortical thickness across the brain.

Longitudinal Changes After Amygdala Surgery for Intractable Aggressive Behavior: Clinical, Imaging Genetics, and Deformation-Based Morphometry Study-A Case Series.

BACKGROUND: Intractable aggressive behavior (iAB) is a devastating behavioral disorder that may affect psychiatric patients. These patients have reduced quality of life, are more challenging to treat as they impose a high caregiver burden and require specialized care. Neuromodulatory interventions targeting the amygdala, a key hub in the circuitry of aggressive behavior (AB), may provide symptom alleviation. OBJECTIVE: To Report clinical and imaging findings from a case series of iAB patients treated with bilateral amygdala ablation. METHODS: This series included 4 cases (3 males, 19-32 years old) who underwent bilateral amygdala radiofrequency ablation for iAB hallmarked by life-threatening self-injury and social aggression. Pre- and postassessments involved full clinical, psychiatric, and neurosurgical evaluations, including scales quantifying AB, general agitation, quality of life, and magnetic resonance imaging (MRI). RESULTS: Postsurgery assessments revealed decreased aggression and agitation and improved quality of life. AB was correlated with testosterone levels and testosterone/cortisol ratio in males. No clinically significant side effects were observed. Imaging analyses showed preoperative amygdala volumes within normal populational range and confirmed lesion locations. The reductions in aggressive symptoms were accompanied by significant postsurgical volumetric reductions in brain areas classically associated with AB and increases in regions related to somatosensation. The local volumetric reductions are found in areas that in a normal brain show high expression levels of genes related to AB (eg, aminergic transmission) using gene expression data provided by the Allen brain atlas. CONCLUSION: These findings provide new insight into the whole brain neurocircuitry of aggression and suggest a role of altered somatosensation and possible novel neuromodulation targets.

Predicting optimal deep brain stimulation parameters for Parkinson's disease using functional MRI and machine learning.

Commonly used for Parkinson's disease (PD), deep brain stimulation (DBS) produces marked clinical benefits when optimized. However, assessing the large number of possible stimulation settings (i.e., programming) requires numerous clinic visits. Here, we examine whether functional magnetic resonance imaging (fMRI) can be used to predict optimal stimulation settings for individual patients. We analyze 3 T fMRI data prospectively acquired as part of an observational trial in 67 PD patients using optimal and non-optimal stimulation settings. Clinically optimal stimulation produces a characteristic fMRI brain response pattern marked by preferential engagement of the motor circuit. Then, we build a machine learning model predicting optimal vs. non-optimal settings using the fMRI patterns of 39 PD patients with a priori clinically optimized DBS (88% accuracy). The model predicts optimal stimulation settings in unseen datasets: a priori clinically optimized and stimulation-naïve PD patients. We propose that fMRI brain responses to DBS stimulation in PD patients could represent an objective biomarker of clinical response. Upon further validation with additional studies, these findings may open the door to functional imaging-assisted DBS programming.

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.