Cordotomy under general anesthesia for a pediatric palliative patient: illustrative case.

BACKGROUND: Computed tomography (CT)-guided cordotomy has been shown to be a safe and effective method for treating cancer pain in adults in a palliative care setting. Its effectiveness has been rarely reported in children. During cordotomy, patient feedback is considered essential. Unfortunately, in this report, the featured patient's age and demeanor precluded an awake cordotomy. The authors report the first case, to their knowledge, of percutaneous cordotomy with the patient under general anesthesia. OBSERVATIONS: An 11-year-old boy with osteosarcoma of the right pelvis presented with medically refractory unilateral nociceptive pain. The pain prevented ambulation, interfered with sleep, was the focus of his concern, and could not be relieved without sedation. A left percutaneous CT-guided cervical cordotomy while he was under general anesthesia was performed without complication and provided sufficient pain relief to allow ambulation and restorative sleep. Pain was no longer an issue for the patient and his family. LESSONS: CT-guided percutaneous cervical cordotomy can be accomplished in a pediatric patient under general anesthesia. The risks of cordotomy under general anesthesia without patient feedback must be weighed against the opportunity to improve palliative care. https://thejns.org/doi/abs/10.3171/CASE2427.

Non-Motor Effects of Low-Frequency Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease: A Systematic Review.

INTRODUCTION: Deep brain stimulation of the subthalamic nucleus is an effective therapy for the motor symptoms of Parkinson's disease (PD). Typically, stimulation is applied at a high frequency (≥100 Hz) to alleviate motor symptoms. However, the effects on non-motor symptoms can be variable. Low-frequency oscillations are increasingly recognized as playing an important role in the non-motor functions of the subthalamic nucleus. Therefore, it has been hypothesized that low-frequency stimulation of the subthalamic nucleus (<100 Hz) may have a direct effect on these non-motor functions, thereby preferentially impacting non-motor symptoms of PD. Despite important therapeutic implications, the literature on this topic has not been summarized. METHOD: To understand the current state of the field, we performed a comprehensive systematic review of the literature assessing the non-motor effects of low-frequency stimulation of the subthalamic nucleus in PD. We performed a supplementary meta-analysis to assess the effects of low- versus high-frequency stimulation on verbal fluency outcomes. RESULTS: Our search returned 7,009 results, of which we screened 4,199 results. A total of 145 studies were further assessed for eligibility, and a total of 21 studies met our inclusion criteria, representing 297 patients. These studies were a mix of case reports and control trials. The four clinical outcomes measured were sleep, sensory perception, cognition, and mood. A supplementary meta-analysis of six studies investigating the impact of low-frequency stimulation on verbal fluency did not find any significant results when pooling across subgroups. CONCLUSION: LFS of the STN may have benefits on a range of cognitive and affective symptoms in PD. However, current studies in this space are heterogeneous, and the effect sizes are small. Factors that impact outcomes can be divided into stimulation and patient factors. Future work should consider the interactions between stimulation location and stimulation frequency as well as how these interact depending on the specific non-motor phenotype.

Bilateral Anterior Capsulotomy for Treatment-Resistant Obsessive-Compulsive Disorder.

INTRODUCTION: Ablative surgery is an intervention of last resort for treatment-resistant obsessive-compulsive disorder (TROCD). Our center has been using bilateral anterior capsulotomy (BAC) for the past 20 years for patients eligible for limbic surgery. This report details our experience with BAC for TROCD. METHOD: Five patients with OCD met eligibility criteria for BAC. Entry protocols were complex and took around 6 months to complete. Stereotactic radiofrequency was used to produce the capsulotomies. Lesion length varied between 5.7 and 16.9 mm in the coronal plane. Patients were followed between 4 and 20 years. RESULTS: All 5 patients (100%) were responders as defined by the widely accepted criteria of a reduction of ≥35% in Yale-Brown Obsessive Compulsive Scale (YBOCS) score at 18-month follow-up. Four patients remained responders at the 48 months. One patient was lost to follow-up. Responder status when viewed from the perspective of the YBOCS was sustained over the 4- to 20-year follow-up with one relapse 19 years postsurgery when medications were discontinued. Real-world psychiatric outcomes were different as other vulnerabilities surfaced illustrating the multifactorial determinants of mental health. No patient had any significant long-term neurocognitive or physical side effects. CONCLUSION: BAC should remain an option of last resort for patients with severe OCD who remain unresponsive to all other interventions.

Deep Brain Stimulation Improves Symptoms of Spasmodic Dysphonia Through Targeting of Thalamic Sensorimotor Connectivity.

BACKGROUND AND OBJECTIVES: Spasmodic dysphonia is a dystonia of the vocal chords producing difficulty with speech. Current hypotheses are that this is a condition of dysregulated thalamic sensory motor integration. A recent randomized controlled trial of thalamic deep brain stimulation (DBS) demonstrated its safety and efficacy. Our objective was to determine whether the outcome could be predicted by stimulation of thalamic sensorimotor areas and adjacent white matter connectivity as assessed by diffusion tractography. METHODS: A cohort of 6 participants undergoing thalamic DBS for adductor spasmodic dysphonia was studied. Electrodes were localized with the Lead-DBS toolbox. Group-based analyses were performed with atlases, coordinates, and using voxel-based symptom mapping. Diffusion tensor imaging (3 T, 64 directions, 2-mm isotropic) was used to perform individual probabilistic tractography (cerebellothalamic tract and pallidothalamic tract) and segmentation of the thalamus. Monopolar review was performed at 0.5 V and binarised as effective or ineffective. RESULTS: Effective contacts stimulated more of thalamic sensorimotor areas than ineffective contacts (P < .05, false discovery rate corrected). This effect was consistent across analytical and statistical techniques. Group-level and tractography analyses did not identify a specific "sweet spot" suggesting the benefit of DBS is derived from modulating individual thalamic sensorimotor areas. Stimulations at 1 year involved predicted thalamic sensorimotor regions with additional cerebellothalamic tract involvement. CONCLUSION: Stimulation of thalamic sensorimotor areas was associated with improvement in symptoms of spasmodic dysphonia. These data are consistent with DBS acting on pathophysiologically dysregulated thalamic sensorimotor integration in spasmodic dysphonia.

Ventral targeted anterior capsulotomy for treatment-resistant depression and obsessive-compulsive disorder: A treatment method with cases.

BACKGROUND: Ablative surgery using bilateral anterior capsulotomy (BAC) is an option for treatment resistant depression (TRD) and obsessive-compulsive disorder (TROCD). The location and extent of the lesion within anterior limb of the internal capsule (ALIC) remains uncertain. Accumulating evidence has suggested that the lesion should be located ventrally while limiting the dorsal extent. Our center is now targeting specific fiber tracts within the lower half of the ALIC. METHOD: Presurgical diffusion tensor Magnetic Resonance Imaging (MRI) was used to identify individual fibre tracts within the ventral aspect of the ALIC in the last two patients who underwent BAC at our center. One patient had TRD and the other had both TROCD and TRD. Radiofrequency-induced thermal lesions were created in the identified targets with lesion volumes between 20 and 229 mm3 (average 95 mm3). FINDINGS: Both patients were responders with neither experiencing significant side effects including compromised executive functions. LIMITATIONS: The generalizability of our findings is limited because the outcome is based on two subjects. CONCLUSION: This work suggests that BAC can be individually tailored and more limited to the ventral aspect of the ALIC and is effective and safe for TRD and TROCD. Accumulating data also suggests that to be clinically effective the length of the capsulotomy should be about 10mm. BAC's use may increase with the growing utilization and mastery of magnetic resonance guided focused ultrasound.

Mapping the Landscape of Equitable Access to Advanced Neurotechnologies in Canada.

Geographic, social, political, and economic factors shape access to advanced neurotechnologies, yet little previous research has explored the barriers, enablers, and areas of opportunity for equitable and meaningful access for diverse patient communities across Canada. We applied a mixed-mode approach involving semi-structured interviews and rating scale questions to consult with 24 medical experts who are involved in the care of patients who undergo functional neurosurgery targeting the brain. Seven major themes emerged from the qualitative analysis: Health care system, Neurotechnology features, Patient demographics, Target condition features, Ethics, Upstream barriers and enablers, and Areas of opportunity. Descriptive statistics of the Likert-scale responses suggest that interviewees perceive a disparity between the imperative of access to advanced neurotechnologies for people living in rural and remote areas and the likelihood of achieving such access. The results depict a complex picture of access to functional neurosurgery in Canada with pockets of excellence and a motivation to improve the availability of care for vulnerable populations through the expansion of distributed care models, improved health care system efficiencies, increasing funding and support for patient travel, and increasing awareness about and advocacy for advanced neurotechnologies.

The Location of the Parasympathetic Fibres within the Vagus Nerve Rootlets: A Case Report and a Review of the Literature.

The vagus nerve has motor, sensory, and parasympathetic components. Understanding the nerve's internal anatomy, its variations, and relationship to the glossopharyngeal nerve are crucial for neurosurgeons decompressing the lower cranial nerves. We present a case report demonstrating the location of the parasympathetic fibres within the vagus nerve rootlets. A 47-year-old woman presented with a 1-year history of medically refractory left-sided glossopharyngeal neuralgia and a more recent history of left-sided hemi-laryngopharyngeal spasm. magnetic resonance imaging showed her left posterior inferior cerebellar artery distorting the lower cranial nerves on the affected left side. The patient consented to microvascular decompression of the lower cranial nerves with possible sectioning of the glossopharyngeal and upper sensory rootlets of the vagus nerve. During surgery, electrical stimulation of the most caudal rootlet of the vagus nerve triggered profound bradycardia. None of the more rostral rootlets had a similar parasympathetic response. This case is the first demonstration, to our knowledge, of the location of the cardiac parasympathetic fibres within the human vagus nerve rootlets. This new understanding of the vagus nerve rootlets' distribution of pure sensory (most rostral), motor/sensory (more caudal), and parasympathetic (most caudal) fibres may lead to a better understanding and diagnosis of the vagal rhizopathies. Approximately 20% of patients with glossopharyngeal neuralgia also have paroxysmal cough. This could be due to the anatomical juxtaposition of the IXth cranial nerve with the rostral vagal rootlets with pure sensory fibres (which mediate a tickling sensation in the lungs). A subgroup of patients with glossopharyngeal neuralgia have neuralgia-induced syncope. The cause of this rare condition, "vago-glossopharyngeal neuralgia," has been debated since it was first described by Riley in 1942. Our case supports the theory that this neuralgia-induced bradycardia is reflexively mediated through the brainstem with afferent impulses in the IXth and efferent impulses in the Xth cranial nerve. The rarer co-occurrence of glossopharyngeal neuralgia with hemi-laryngopharyngeal spasm (as seen in this case) may be explained by the proximity of the IXth nerve with the more caudal vagus rootlets which have motor (and probably sensory) supply to the throat. Finally, if there is a vagal rhizopathy related to compression of its parasympathetic fibres, one would expect it to be at the most caudal rootlet of the vagus nerve.

Non-contrast-enhancing subdural empyema: illustrative case.

BACKGROUND: Subdural empyema (SDE) is a life-threatening intracranial infection that, without timely surgical intervention and appropriate antibiotic treatment, is inevitably fatal. SDE is classically recognized on brain imaging as a subdural collection surrounded by a contrast-enhancing ring. OBSERVATIONS: The authors describe the case of a 41-year-old male with clinical features consistent with SDE but without any contrast enhancement on multiple computed tomography scans obtained more than 48 hours apart. Given the high clinical suspicion for SDE, a craniotomy was performed that demonstrated frank pus that eventually grew Streptococcus pyogenes. LESSONS: This case demonstrates that SDE may present without ring enhancement on contrast-enhanced imaging. In critically ill patients with a high clinical suspicion for SDE despite lack of contrast enhancement, we demonstrate that exploratory burr holes or craniotomy can provide diagnostic confirmation and source control.

Ablation Surgeries for Treatment-Resistant Depression: A Meta-Analysis and Systematic Review of Reported Case Series.

BACKGROUND AND OBJECTIVES: Ablative lesion procedures remain as the last option in treatment of refractory depression. Contemporary ablative psychosurgeries involve producing lesions in the anterior limb of the internal capsule (bilateral anterior capsulotomy - BAC), the supragenual anterior cingulate gyrus and cingulum (bilateral anterior cingulotomy - BACING), and subgenual anterior cingulate gyrus and subcortical orbitofrontal white matter (bilateral subcaudate tractotomy - BST). A combination of BACING and BST is known as limbic leukotomy (bilateral limbic leukotomy - BLL). All procedures claim some success, but cohorts are small, depression assessment instruments differ, and inclusion and outcome criteria and follow-up duration vary. In some cohorts, more than one type of surgery was performed in several patients, further confounding interpreting the available data. Current evidence is equivocal on which surgical target works best. Method and Aim: This systematic review and meta-analysis using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standard on published cohorts was conducted to review and identify which is the best standalone ablative procedure for treatment-resistant depression (TRD) based on response rate (event rate) and adverse-effect profile using the Comprehensive Meta-Analysis software. RESULTS AND CONCLUSION: As a standalone neurosurgical procedure, we found that BAC appears to be the most effective and safest of all the ablative targets for TRD. A major limitation of this conclusion is the paucity of published case series where sample sizes are small and all are open label.

Sweet spots of standard and directional leads in patients with refractory essential tremor: white matter pathways associated with maximal tremor improvement.

OBJECTIVE: In patients with essential tremor (ET) treated with standard deep brain stimulation (sDBS) whose ET had progressed and who no longer received optimal benefit from sDBS, directional deep brain stimulation (dDBS) may provide better tremor control. Current steering may provide better coverage of subcortical structures related to tremor control in patients with ET and significant progression without optimal response to sDBS. METHODS: This study included 6 patients with ET initially treated with sDBS whose tremor later progressed and who then underwent reimplantation with dDBS to optimize their tremor control. To investigate the differences in the local effects of sDBS and dDBS, the authors generated the volume of tissue activation (VTA) to calculate the sweet spots associated with the best possible tremor control with no side effects. Then, to investigate the anatomical structures associated with maximal tremor control, the white matter pathways of the posterior subthalamic areas (PSAs) were generated and their involvement with the sDBS and dDBS sweet spots was calculated. RESULTS: Tremor improvement was significantly better with dDBS (68.4%) than with sDBS (48.7%) (p = 0.017). The sDBS sweet spot was located within the ventral intermediate nucleus, whereas the sweet spot of the dDBS was mainly located within the PSA. The sweet spots of both sDBS and dDBS involved a similar portion of the cerebellothalamic pathway. However, the dDBS had greater involvement of the pallidofugal pathways than the sDBS. CONCLUSIONS: In patients with ET treated with sDBS who later had ET progression, dDBS provided better tremor control, which was related to directionality and a more ventral position. The involvement of both the cerebellothalamic and pallidofugal pathways obtained with dDBS is associated with additional improvement over the sDBS.

Directional Deep Brain Stimulation Can Target the Thalamic "Sweet Spot" for Improving Neuropathic Dental Pain.

BACKGROUND: Neuropathic dental pain (NDP) is a chronic pain condition that is notoriously difficult to treat. To date, there are no deep brain stimulation (DBS) studies on this specific pain condition and no optimal target or "sweet spot" has ever been defined. OBJECTIVE: To determine the optimal thalamic target for improving this condition by utilizing the steering abilities of a directional DBS electrode (Vercise CartesiaTM Model DB-2202-45, Boston Scientific). METHODS: A literature search and review of our database identified 3 potential thalamic targets. A directional lead was implanted in a patient with NDP and its current steering used to test the effects in each nucleus. The patient reported her pain after 2 wk of stimulation in a prospective randomized blinded trial of one. Quality of life measurements were performed before and after 3 mo on their best setting. RESULTS: We identified 3 potential nuclei: the centromedian (CM), ventral posterior medial (VPM), and anterior pulvinar. The best results were during VPM stimulation (>90% reduction in pain) and CM stimulation (50% reduction). Following 3 mo of VPM-DBS in combination of lateral CM stimulation, their pain disability index dropped (from 25 to 0) and short form 36 improved (from 67.5 to 90). CONCLUSION: VPM stimulation in combination with CM stimulation is a promising target for NDP. DBS electrode directionality can be used to test multiple targets and select a patient specific "sweet spot" for NDP treatment.

Thalamic Deep Brain Stimulation for Spasmodic Dysphonia: A Phase I Prospective Randomized Double-Blind Crossover Trial.

BACKGROUND: Adductor spasmodic dysphonia (SD) is a dystonia of the vocal folds causing difficulty with speech. The current standard of care is repeated botulinum toxin injections to weaken the adductor muscles. We sought to ameliorate the underlying neurological cause of SD with a novel therapy-deep brain stimulation (DBS). OBJECTIVE: To assess the safety of DBS in SD through phase I trial, and to quantify the magnitude of any benefit. METHODS: Six patients had left ventral intermediate nucleus (Vim) thalamic DBS and were randomized to 3 mo blinded-DBS "on" or "off" followed by a crossover. Primary outcomes were quality of life and quality of voice during the blinded phase. Patients continued with open-DBS "on." Secondary outcomes were comparisons of pre- and 1-yr cognitive, mood, and quality of life. This trial was registered with ClinicalTrials.gov (NCT02558634). RESULTS: There were no complications. Every patient reported an improvement in quality of life (P = .07) and had an improvement in quality of their voice (P = .06) when their blinded DBS was "on" versus "off." The trend did not reach statistical significance with the small sample size. Secondary outcomes showed no difference in cognition, an improvement in mood, and quality of life at 1 yr. CONCLUSION: This phase I randomized controlled trial confirmed that DBS can be performed safely in patients with SD. Blinded DBS produced a strong trend toward improved quality of life and objective quality of voice despite the small sample size. The cerebellar circuit, not the pallidal circuit, appears to be crucial for motor control of the vocal folds.

Tractography-Guided Anterior Capsulotomy for Major Depression and Obsessive-Compulsive Disorder: Targeting the Emotion Network.

BACKGROUND: Bilateral anterior capsulotomy (BAC) is an effective surgical option for patients with treatment-resistant major depression (TRMD) and treatment-resistant obsessive-compulsive disorder (TROCD). The size of the lesion and its precise dorsal-ventral location within the anterior limb of the internal capsule (ALIC) remain undefined. OBJECTIVE: To present a method to identify the trajectories of the associative and limbic white matter pathways within the ALIC for targeting in BAC surgery. METHODS: Using high-definition tractography, we prospectively tested the feasibility of this method in 2 patients with TRMD and TROCD to tailor the capsulotomy lesion to their limbic pathway. RESULTS: The trajectories of the associative and limbic pathways were identified in the ALIC of both patients and we targeted the limbic pathways by defining the dorsal limit of the lesion in a way to minimize the damage to the associative pathways. The final lesions were smaller than those that have been previously published. This individualized procedure was associated with long-term benefit in both patients. CONCLUSION: Tractography-guided capsulotomy is feasible and was associated with long-term benefit in patients with TRMD and TROCD.

Tremor and Quality of Life in Patients With Advanced Essential Tremor Before and After Replacing Their Standard Deep Brain Stimulation With a Directional System.

OBJECTIVES: Patients with essential tremor treated with thalamic deep brain stimulation may experience increased tremor with the progression of their disease. Initially, this can be counteracted with increased stimulation. Eventually, this may cause unwanted side-effects as the circumferential stimulation from a standard ring contact spreads into adjacent regions. Directional leads may offer a solution to this clinical problem. We aimed to compare the ability of a standard and a directional system to reduce tremor without side-effects and to improve the quality of life for patients with advanced essential tremor. MATERIALS AND METHODS: Six advanced essential tremor patients with bilateral thalamic deep brain stimulation had their standard system replaced with a directional system. Tremor rating scale scores were prospectively evaluated before and after the replacement surgery. Secondary analyses of quality of life related to tremor, voice, and general health were assessed. RESULTS: There was a significantly greater reduction in tremor without side-effects (p = 0.017) when using the directional system. There were improvements in tremor (p = 0.031) and voice (p = 0.037) related quality of life but not in general health for patients using optimized stimulation settings with the directional system compared to the standard system. CONCLUSIONS: In this cohort of advanced essential tremor patients who no longer had ideal tremor reduction with a standard system, replacing their deep brain stimulation with a directional system significantly improved their tremor and quality of life. Up-front implantation of directional deep brain stimulation leads may provide better tremor control in those patients who progress at a later time point.

Deep Brain Stimulation for Spasmodic Dysphonia: A Blinded Comparison of Unilateral and Bilateral Stimulation in Two Patients.

Deep brain stimulation (DBS) is a promising new therapy for patients with spasmodic dysphonia (SD). The preliminary results from our randomized controlled trial showed good clinical effects with unilateral left thalamic stimulation in 6 right- handed patients. This suggests that the pathological process underpinning SD may have a "hemisphere dominant" pathway. We describe 2 patients with concurrent essential tremor and SD who had previously undergone bilateral thalamic DBS for their limb tremor. Both patients experienced an unanticipated improvement of their SD symptoms. One patient was right-handed, and the other was mixed left-handed. To investigate the amount of SD improvement following DBS therapy in each hemisphere, 4 different settings were tested: both sides on, left side on, right side on, and both sides off. Both patients most improved following bilateral stimulation. There was, however, a powerful unilateral benefit in both patients with only a small additional benefit from bilateral stimulation. The right-handed patient improved most with left-hemisphere stimulation whereas the mixed left-handed patient improved most with right hemisphere stimulation. There was some discrepancy between the two tests applied in the second patient reflecting the known difficulties to evaluate vocal symptom improvement in SD. We discuss the possible correlation of handedness and speech hemisphere dominance as well as the need for more reliable tests to measure SD severity. Ultimately, we recommend a bilateral approach for future studies, using a patient perception test as the primary outcome and functional imaging to further investigate the correlation of handedness and the amount of hemisphere dominance in SD.

Hemi-laryngopharyngeal Spasm (HeLPS): Defining a New Clinical Entity.

OBJECTIVE: Hemi-laryngopharyngeal spasm (HeLPS) has recently been described in the neurosurgical literature as a cause of intermittent laryngopharyngeal spasm and cough due to vascular compression of the vagus nerve at the cerebellopontine angle. We present the diagnostic criteria for this syndrome. METHODS: A retrospective chart review of six patients with HeLPS and three patients misdiagnosed with this condition are presented. All patients were diagnosed and treated at a tertiary care academic centre from July 2013 to July 2017. RESULTS: Patients with HeLPS had five defining characteristics: 1) All patients had symptoms of episodic laryngopharyngeal spasm and coughing. Patients were asymptomatic between episodes and were refractory to speech therapy and reflux management. 2) Laryngoscopy showed hyperactive twitching of the ipsilateral vocal fold in two of the six patients. No other inter-episodic abnormalities were seen. 3) Botulinum toxin A injections into the thyroarytenoid muscle on the affected ipsilateral side reduced laryngopharyngeal spasms. Botulinum toxin injection in the contralateral thyroarytenoid muscle did not improve laryngopharyngeal spasm. 4) Magnetic resonance imaging revealed ipsilateral neurovascular compression of the vagus nerve rootlets by the posterior inferior cerebellar artery. 5) Microvascular decompression (MVD) surgery of the ipsilateral vagus nerve resolved all symptoms (follow-up 2-4 years). CONCLUSION: The diagnostic criteria for hemi-laryngopharyngeal spasm (HeLPS) are proposed. Otolaryngology recognition of this new clinical entity may lead to a surgical cure and avoid the unnecessary therapies associated with misdiagnosis. LEVEL OF EVIDENCE: 4.

Hypoactivity in the Paraterminal Gyrus Following Bilateral Anterior Capsulotomy.

OBJECTIVE: Bilateral anterior capsulotomy (BAC) is one of the ablative neurosurgical procedures used to treat major depressive disorder or obsessive-compulsive disorder when all other therapies fail. Tristolysis, a reduction in sadness, is the most striking clinical effect of BAC and is seen in the first 1 to 2 weeks after surgery. This retrospective study measured regional cerebral blood flow (rCBF) following surgery to identify which cortical regions were impacted and could account for this clinical effect. METHODS: All patients had their capsulotomies done in Vancouver by the same team. Pre- and postoperative single-photon emission computed tomography perfusion scans were analyzed for 10 patients with major depressive disorder and 3 with obsessive-compulsive disorder. rCBF was measured semiquantitatively by calculating the ratio between an identified region of interest and a whole brain reference area. RESULTS: Decreased rCBF was found in the paraterminal gyri. Increased rCBF was found in the dorsolateral prefrontal cortices and in the left lateral temporal lobe. CONCLUSIONS: BAC causes hypoactivity in the paraterminal gyri and is the most likely explanation for its tristolytic effect, suggesting that the paraterminal gyrus is the limbic cortical locus for the emotion of sadness. Increased activity in the dorsolateral prefrontal cortices may be occurring via connectional diaschisis, and suppression by overactive paraterminal gyri during depression may account for some of the neurocognitive deficits observed during depressive episodes.

Modulation of Nigrofugal and Pallidofugal Pathways in Deep Brain Stimulation for Parkinson Disease.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established surgical therapy for patients with Parkinson disease (PD). OBJECTIVE: To define the role of adjacent white matter stimulation in the effectiveness of STN-DBS. METHODS: We retrospectively evaluated 43 patients with PD who received bilateral STN-DBS. The volumes of activated tissue were analyzed to obtain significant stimulation clusters predictive of 4 clinical outcomes: improvements in bradykinesia, rigidity, tremor, and reduction of dopaminergic medication. Tractography of the nigrofugal and pallidofugal pathways was performed. The significant clusters were used to calculate the involvement of the nigrofugal and pallidofugal pathways and the STN. RESULTS: The clusters predictive of rigidity and tremor improvement were dorsal to the STN with most of the clusters outside of the STN. These clusters preferentially involved the pallidofugal pathways. The cluster predictive of bradykinesia improvement was located in the central part of the STN with an extension outside of the STN. The cluster predictive of dopaminergic medication reduction was located ventrolateral and caudal to the STN. These clusters preferentially involved the nigrofugal pathways. CONCLUSION: Improvements in rigidity and tremor mainly involved the pallidofugal pathways dorsal to the STN. Improvement in bradykinesia mainly involved the central part of the STN and the nigrofugal pathways ventrolateral to the STN. Maximal reduction in dopaminergic medication following STN-DBS was associated with an exclusive involvement of the nigrofugal pathways.