Category: Functional

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Mapping the Functional Boundaries of the Speech Articulation Network Using Positive and Negative Direct Electrical Stimulation With Resting-State Functional MRI

Neurosurgery 98:577–587, 2026

This clinical research integrates positive and negative direct electrical stimulation (DES) with presurgical resting-state fMRI to refine the speech articulation network (SAN) atlas in glioma patients. Analyzing 25 patients, the study maps DES-positive and DES-negative seed-based connectivity, compares anticorrelated networks, and evaluates sensitivity and specificity across group-frequency thresholds.

Key findings show DES-positive sites robustly identify bilateral SAN regions (rolandic operculum, inferior frontal and superior temporal gyri), while DES-negative points delineate functional borders and improve atlas specificity; a 41% SAN-positive threshold yields approximately 80% sensitivity and specificity for clinical use.

Resting-state fMRI and DES: Resting-state functional MRI (rs-fMRI) is a noninvasive tool for mapping brain networks, while direct electrical stimulation (DES) during awake surgery (AwS) is the gold standard for causally identifying functional brain regions, especially for speech articulation mapping in glioma patients.

Inclusion of DES-negative points: Incorporating both DES-positive (eliciting function) and DES-negative (no function elicited) points enables more precise mapping of the speech articulation network (SAN) and its functional borders, improving specificity and sensitivity compared to using only positive points.

Comprehensive SAN atlas: A new SAN atlas was created from 25 glioma patients using 32 DES-positive and 42 DES-negative points, with presurgical rs-fMRI seed-based connectivity analysis, providing a more accurate and clinically relevant definition of the SAN.

Distinct connectivity patterns: DES-positive points consistently mapped the SAN to bilateral rolandic operculum, inferior frontal gyrus, and superior temporal gyrus, while DES-negative points revealed distinct, only partially overlapping connectivity patterns, helping delineate the SAN’s functional borders.

Threshold for clinical use: A 41% frequency threshold for the SAN-positive network achieves approximately 80% sensitivity and specificity, offering a practical balance for clinical application in presurgical planning.

Functional borders and overlap: Minimal overlap between SAN-positive and SAN-negative networks identifies functional borders, especially in the precentral sulcus and inferior frontal gyrus, aiding neurosurgeons in distinguishing critical from non-critical areas during mapping.

Clinical implications: Defining precise SAN borders improves intraoperative decision-making, reduces irrelevant stimulation, shortens mapping time, and enhances safety in both awake and asleep brain surgeries.

Limitations and future directions: The study’s limitations include sample size, heterogeneity, and MRI field strength; future research should use larger, more homogeneous cohorts and higher-resolution imaging to further refine SAN mapping.

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Central thalamic deep brain stimulation for disorders of consciousness: an individual participant data meta-analysis

J Neurosurg 143:1217–1226, 2025

This individual participant data meta-analysis evaluates central thalamic deep brain stimulation (DBS) for chronic disorders of consciousness, pooling 49 patients from seven centers to assess neurological outcomes via the JFK Coma Recovery Scale–Revised. Results show modest mean CRS-R improvement, with age and shorter delay to implantation predicting better gains, but insufficient evidence that DBS alters the natural recovery trajectory.

The report details heterogeneity in targets, stimulation schedules, and methodological limitations—no randomized controls, selection bias, and variable reporting—highlighting the need for matched comparative studies, standardized outcome metrics, and refined targeting (CL vs CM-Pf/DTTm) to determine DBS efficacy and optimize patient selection.

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Multi-institutional recommendations on the use of 7T MRI in deep brain stimulation

J Neurosurg 143:1165–1175, 2025

This multi-institutional review presents consensus recommendations for integrating 7T ultrahigh-field MRI into deep brain stimulation (DBS) workflows, drawing on experience from over 1,000 procedures. It summarizes technical challenges—B1+ heterogeneity, susceptibility and gradient nonlinear distortions—and practical solutions for acquisition, distortion correction, and coregistration to ensure stereotactic accuracy.

The document details optimized sequences and target-specific imaging strategies (STN, GPi, thalamic nuclei, ANT, CM), advanced modalities (DTI/DiMANI, QSM, tractography), and multidisciplinary workflow considerations to improve patient-specific anatomical and connectivity-based DBS targeting and programming.

• 7T MRI Advantages: Ultrahigh-field 7T MRI provides superior spatial resolution, signal-to-noise ratio, and tissue contrast, enabling clearer visualization of deep brain structures critical for deep brain stimulation (DBS) targeting compared to 1.5T and 3T MRI.

• Improved DBS Targeting: 7T MRI enhances direct anatomical and connectivity-based targeting for DBS, supporting more precise, patient-specific electrode placement for Parkinson’s disease, essential tremor, and epilepsy.

• Key Technical Challenges: 7T MRI introduces unique challenges including B1+ transmit field inhomogeneity, increased image distortions (gradient nonlinearity and susceptibility), and chemical shift artifacts, all of which require specialized correction and protocol optimization.

• Distortion Correction and Coregistration: Accurate DBS planning with 7T MRI demands robust correction for gradient and susceptibility distortions, careful coregistration with stereotactic CT, and often manual or nonlinear registration adjustments for optimal anatomical alignment.

• Recommended Imaging Sequences: Specific 7T MRI sequences, such as T2-weighted, FGATIR, MP2RAGE, SWI, QSM, and advanced diffusion imaging (DTI/DiMANI), are recommended for visualizing common DBS targets (STN, GPi, thalamic nuclei), each offering distinct advantages for different structures.

• Connectivity and Tractography: Advanced diffusion MRI at 7T allows submillimetric tractography, enabling functional parcellation of DBS targets (e.g., STN, GPi, DRTT), which can improve patient outcomes by supporting symptom- and network-specific targeting.

• Clinical Impact: Implementation of 7T MRI in over 1000 DBS procedures across multiple centers has demonstrated that, with appropriate workflow and expertise, technical challenges can be managed and targeting accuracy and patient outcomes can be improved.

• Multidisciplinary Collaboration: Effective use of 7T MRI for DBS requires close collaboration between neurosurgeons, MR technicians, physicists, and neuroradiologists to optimize protocols and address the complexity of ultrahigh-field imaging

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Afferent and efferent fiber systems of the human amygdala: anatomical, pathophysiological, and clinical significance

J Neurosurg 143:1202–1216, 2025

This paper presents a comprehensive neuroanatomical and radiological analysis of the human amygdala, detailing its nuclei, major afferent and efferent fiber systems, and spatial relationships using white matter fiber dissection and diffusion tensor tractography. The authors synthesize structural descriptions with functional roles in emotion, memory, olfaction, and seizure propagation, emphasizing clinical relevance for neuroclinicians.

The study maps key pathways—the ansa peduncularis, ventral and dorsal amygdalofugal routes, stria terminalis, medial forebrain bundle, olfactory striae, and stria medullaris thalami—correlating anatomy with neurosurgical applications such as deep brain stimulation and lesion resection. Anatomical findings are supported by illustrative dissections, tractography, and a clinical cavernoma case demonstrating surgical implications.

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A Speech Neuroprosthesis in the Frontal Lobe and Hippocampus: Decoding High-Frequency Activity into Phonemes

Neurosurgery 96:356–364, 2025

Loss of speech due to injury or disease is devastating. Here, we report a novel speech neuroprosthesis that artificially articulates building blocks of speech based on high-frequency activity in brain areas never harnessed for a neuroprosthesis before: anterior cingulate and orbitofrontal cortices, and hippocampus.

METHODS: A 37-year-old male neurosurgical epilepsy patient with intact speech, implanted with depth electrodes for clinical reasons only, silently controlled the neuroprosthesis almost immediately and in a natural way to voluntarily produce 2 vowel sounds.

RESULTS: During the first set of trials, the participant made the neuroprosthesis produce the different vowel sounds artificially with 85% accuracy. In the following trials, performance improved consistently, which may be attributed to neuroplasticity. We show that a neuroprosthesis trained on overt speech data may be controlled silently.

CONCLUSION: This may open the way for a novel strategy of neuroprosthesis implantation at earlier disease stages (eg, amyotrophic lateral sclerosis), while speech is intact, for improved training that still allows silent control at later stages. The results demonstrate clinical feasibility of direct decoding of high-frequency activity that includes spiking activity in the aforementioned areas for silent production of phonemes that may serve as a part of a neuroprosthesis for replacing lost speech control pathways.

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Subtemporal Approach for the Treatment of Ruptured and Unruptured Distal Basilar Artery Aneurysms: Is There a Contemporary Use?

Operative Neurosurgery 27:581–596, 2024

Distal basilar artery aneurysms (DBAs) are high-risk lesions for which endovascular treatment is preferred because of their deep location, yet indications for open clipping nonetheless remain. The subtemporal approach allows for early proximal control and direct visualization of critical posterior perforating arteries, especially for posterior-projecting aneurysms. Our objective was to describe our clinical experience with the subtemporal approach for clipping DBAs in the evolving endovascular era.

METHODS: This was a retrospective, single-institution case series of patients with DBAs treated with microsurgery over a 21-year period (2002-2023). Demographic, clinical, and surgical data were collected for analysis.

RESULTS: Twenty-seven patients underwent clipping of 11 ruptured and 16 unruptured DBAs with a subtemporal approach (24 female; mean age 53 years). Ten patients had expanded craniotomies for treatment of additional aneurysms. The aneurysm occlusion rate was 100%. Good neurological outcomes as defined by the modified Rankin Scale score ≤2 and Glasgow Outcome Scale score ≥4 were achieved in 21/27 patients (78%). Two patients died before hospital discharge, one from vasospasm-induced strokes and another from an intraoperative myocardial infarction.

CONCLUSION: These results demonstrate that microsurgical clip ligation of DBAs using the subtemporal approach remains a viable option for complex lesions not amenable to endovascular management.

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How Accurate Is Frameless Fiducial—Free Deep Brain Stimulation?

Operative Neurosurgery 27:431–439, 2024

Frameless deep brain stimulation (DBS) offers advantages in terms of patient comfort and reduced operative time. However, the need for bony fiducial markers for localization remains a drawback due to the time-consuming and uncomfortable procedure. An alternative localization method involves the direct tracking of an intraoperative 3-dimensional scanner. This study aims to assess the accuracy of the NexFrame frameless DBS system in conjunction with the O-Arm (Medtronic Inc.), both with and without fiducial markers.

METHODS: The locations of 100 DBS leads were determined, with 50 cases using fiducial-free localization and 50 involving fiducial markers. The coordinates were compared with the expected intraoperative targets. Absolute errors in the X, Y, and Z coordinates (ΔX, ΔY, and ΔZ) were calculated, along with the vector error (Euclidean) (vector error square root Δx 2 + Δy 2 + Δz 2 ).

RESULTS: The vector error averaged 1.61 ± 0.49 mm (right) and 1.52 ± 0.60 mm (left) for the group without fiducial bone markers and 1.66 ± 0.69 (right) and 1.44 ± 0.65 mm (left) for the other cohort (P = .76 right; P = .67 left). Absolute errors in the X, Y, and Z coordinates for the fiducial-free group were 0.88 ± 0.55, 0.79 ± 0.45, and 0.79 ± 0.57 mm (right) and 0.72 ± 0.37, 0.78 ± 0.56, and 0.77 ± 0.71 mm (left). For the group with fiducial markers, these errors were 0.87 ± 0.72, 0.92 ± 0.39, and 0.86 ± 0.50 mm (right) and 0.75 ± 0.33, 0.80 ± 0.51, and 0.73 ± 0.64 mm (left) with no statistically significant difference.

CONCLUSION: Our analysis of the accuracy of NexFrame DBS, both with and without fiducial markers, using an intraoperative navigable cone-beam computed tomography, demonstrates that both techniques provide sufficient and equivalent 3-dimensional accuracy.

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

J Neurosurg 141:394–405, 2024

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.

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Ventral amygdalofugal pathway as an integrated surgically important network

J Neurosurg 141:540–554, 2024

The ventral amygdalofugal pathway (VAFP) provides afferent and efferent connections to the amygdala and spans along some of the frequently traversed intra-axial surgical corridors as a dominant fiber bundle. This study aimed to reveal the frequently overlooked VAFP fibers by examining their courses and connections to the basal forebrain, septal region, hypothalamus, thalamus, tegmentum, and brainstem.

METHODS Ten postmortem human brains were used to display the characteristics of the VAFP, and fiber dissection results were compared with those of tractography.

RESULTS From anterior to posterior, the VAFP was separated into 5 different portions: 1) amygdala–substantia innominata; 2) amygdaloseptal (diagonal band of Broca); 3) amygdalo-thalamic; 4) amygdalo-hypothalamic, intermingling with the medial forebrain bundle and extending to the bed nucleus of stria terminalis; and 5) amygdalotegmental. The results of fiber dissections were confirmed with findings obtained from diffusion tensor tractography.

CONCLUSIONS This study supports the concept that interconnected forebrain, diencephalic, mesencephalic, and brainstem connections of the VAFP form an integrated surgically important network. The fiber dissection findings also provide the neuroanatomical basis for VAFP segmentation, which may help neurosurgeons better appreciate the complex microsurgical anatomy of the amygdalar connections. Amygdala–substantia innominata and amygdalotegmental connections are demonstrated for the first time and clarified within the structure of the VAFP.

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Topographical anatomy of the subthalamic region with special interest in the human medial forebrain bundle

J Neurosurg 141:570–580, 2024

The medial forebrain bundle (MFB) is a novel promising deep brain stimulation (DBS) target in severe affective disorders that courses through the subthalamic region according to tractography studies. Its potential therapeutic role arose in connection with the development of hypomania during stimulation of the subthalamic nucleus (STN) in Parkinson’s disease, offering an alternative explanation for the occurrence of this side effect. However, until now its course exclusively described by tractography had not yet been confirmed by any anatomical method. The aim of this study was to fill this gap as well as to provide a detailed description of the fiber tracts surrounding the STN to facilitate a better understanding of the background of side effects occurring during STN DBS.

METHODS Ten human cadaveric brains (20 hemispheres) and 100 healthy subjects (200 hemispheres) from the S500 Release of the Human Connectome Project were involved in this study. Nineteen hemispheres were dissected according to Klingler’s method. One additional hemisphere was prepared for histological examinations to validate the macroscopical results and stained with neurofibril silver impregnation according to Krutsay. The authors also aimed to reconstruct the MFB using tractography and correlated the results with their dissections and histological findings.

RESULTS The white matter connections coursing through the subthalamic region were successfully dissected. The ansa lenticularis, lenticular fasciculus, thalamic fasciculus, ipsi- and contralateral cerebellar fibers, and medial lemniscus were revealed as closely related fiber tracts to the STN. However, the existence of a distinct fiber bundle corresponding to the MFB described by tractography could not be identified. Using tractography, the authors showed that the depiction of the streamlines representing the MFB was also strongly dependent on the threshold parameters.

CONCLUSIONS According to this study’s findings, the streamlines of the MFB described by tractography arise from the limitations of the diffusion-weighted MRI fiber tracking method and actually correspond to subthalamic fiber bundles, especially the ansa lenticularis and lenticular fasciculus, which erroneously continue in the anterior limb of the internal capsule, toward the prefrontal cortex.

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Percutaneous thermal radiofrequency rhizotomy of L2–S1 spinal nerve roots in children with cerebral palsy

Neurosurg Focus 56(6):E7, 2024

This study presents the results of an evaluation of the effectiveness of percutaneous thermal radiofrequency (RF) ablation of spinal nerve roots to reduce spasticity and improve motor function in children with cerebral palsy (CP).

METHODS A retrospective analysis was conducted on the surgical treatment outcomes of 26 pediatric patients with severe CP (Gross Motor Function Classification System levels IV–V). The assessment protocol included muscle tone assessment using the modified Ashworth scale (MAS), evaluation of passive and active range of motion, gait video recording, and locomotor status evaluation using the Gross Motor Function Measure (GMFM)–88 scale. Thermal RF rhizotomy (ablation of spinal nerve roots) was performed on all patients at the L2–S1 levels at 70°C for 90 seconds. The statistical data analysis was conducted using the t-test and Mann-Whitney U-test. A p value < 0.05 was considered statistically significant.

RESULTS Before the operation, the average level of spasticity in the lower-limb muscles of all patients was 3.0 ± 0.2 according to the MAS. In the early postoperative period, the spasticity level in all examined muscle groups significantly decreased to a mean of 1.14 ± 0.15 (p < 0.001). In the long-term postoperative period, the spasticity level in the examined muscle groups averaged 1.49 ± 0.17 points on the MAS (p < 0.001 compared to baseline, p = 0.0416 compared to the early postoperative period). Despite the marked reduction of spasticity in the lower limbs, no significant change in locomotor status according to the GMFM-88 scale was observed in the selected category of patients. In the long-term period, during the control examination of patients, the GMFM-88 level increased on average by 3.6% ± 1.4% (from 22.2% ± 3.1% to 25.8% ± 3.6%).

CONCLUSIONS The findings of this study offer preliminary yet compelling evidence that RF ablation of spinal nerve roots can lead to a significant and enduring decrease in muscle tone among children with severe spastic CP. Further studies and longer-term data of the impact on functionality and quality of life of patients with CP after spinal root RF ablation are needed.

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Neuroprotective Effects of Artificial Cerebrospinal Fluid: Analysis of Brainstem Auditory–Evoked Potential Monitoring During Microvascular Decompression in 117 Consecutive Patients

Neurosurgery 94:1088–1094, 2024

BACKGROUND AND OBJECTIVES: To study the efficacy of irrigation with artificial cerebrospinal fluid (aCSF) for protection of cranial nerves during surgery; the time required for recovery of brainstem auditory–evoked potentials (BAEPs) that would reflect cochlear function was analyzed in comparison with that for saline irrigation.

METHODS: This retrospective study included 117 consecutive patients (95 women, mean age 51.5 ± 11.4 year) who underwent microvascular decompression for hemifacial spasm. During surgery, BAEPs were monitored to avoid damage to the auditory pathways. When a delayed latency of >1 ms or a decrease in amplitude of >50% was detected in BAEP wave V, surgical maneuvers were halted, and the operative field was irrigated with saline or aCSF. Saline was used for irrigation in 58 patients and aCSF in the other 59. The time required for BAEP recovery at the first halt in each patient was analyzed, and the results were compared between the groups.

RESULTS: Surgical procedures were interrupted because of BAEP latency delays or decreases in amplitude in 51 of the patients in the saline group and 54 in the aCSF group. In both groups, the latencies and amplitudes recovered significantly with time and both recovered earlier after aCSF irrigation than after saline irrigation. Hearing outcome was not significantly different between 2 groups.

CONCLUSION: aCSF is effective for protection of cochlear nerve and promotes recovery from transient dysfunction during surgery. The protective effect may be attributed to multiple factors including conditioned pH, electrolyte composition, glucose, and microelements, such as magnesium and phosphate.

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Nonenhancing motor eloquent gliomas: navigated transcranial magnetic stimulation oncobiological signature

J Neurosurg 140:909–919, 2024

Preoperative grading of nonenhancing motor eloquent gliomas is hampered by a lack of specific imaging surrogates. Tumor grading is crucial for the informed consent discussion before tumor resection. In this paper, the authors hypothesized that navigated transcranial magnetic stimulation (nTMS)–derived metrics could provide significant information to distinguish between high- and low-grade motor eloquent gliomas that present as nonenhancing tumors and therefore contribute to improving patient counseling, timing of treatment, preoperative planning, and intraoperative strategies.

METHODS The authors conducted a retrospective single-center cohort study of patients admitted for tumor surgery between January 2018 and April 2022 with a nonenhancing motor eloquent glioma and preoperative bilateral nTMS mapping. nTMS data including resting motor threshold (RMT), interhemispheric RMT ratio (iRMTr), Cortical Excitability Score (CES), area and volume of cortical activation, and motor evoked potential (MEP) characteristics were obtained and integrated with demographic and clinical data.

RESULTS Thirty patients met the inclusion criteria, and 10 healthy participants were recruited for comparison. Seizures were the most common presenting symptom (25 patients) and WHO grade 3 the most common tumor grade (21 patients). The area and volume of functional cortical activation of both the abductor pollicis brevis and first dorsal interosseous muscles were decreased in healthy participants compared with patients with WHO grade 3 glioma (p < 0.05). An abnormal iRMTr for the lower limbs (16.7% [1/6] WHO grade 2, 76.2% [16/21] WHO grade 3, 100% [3/3] WHO grade 4; p = 0.015) and a higher CES (maximal abnormal CES: 0% [0/6] WHO grade 2, 38% [8/21] WHO grade 3, 66.7% [2/3] WHO grade 4; p = 0.010) were associated with the prediction of high-grade lesions. A total of 7280 MEPs were analyzed. A significant increase in the amplitude and a significant decrease in latency in the MEPs for the first dorsal interosseous and abductor digiti minimi muscles (p < 0.0001) were identified in healthy participants compared with WHO grade 3 glioma patients.

CONCLUSIONS Nonenhancing motor eloquent gliomas have a different impact on both anatomical and functional reorganization of motor areas according to their WHO grading.

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Neuronal Encoding of Speech Features in the Human Thalamus in Parkinson’s Disease and Essential Tremor Patients

Neurosurgery 94:307–316, 2024

The human thalamus is known, from stimulation studies and functional imaging, to participate in high-level language tasks. The goal of this study is to find whether and how speech features, in particular, vowel phonemes, are encoded in the neuronal activity of the thalamus, and specifically of the left ventralis intermediate nucleus (Vim), during speech production, perception, and imagery.

METHODS: In this cross-sectional study, we intraoperatively recorded single neuron activity in the left Vim of eight neurosurgical patients with Parkinson’s disease (PD) (n = 4) or essential tremor (n = 4) undergoing implantation of deep brain stimulation (n = 3) or radiofrequency lesioning (n = 5) while patients articulated the five monophthongal vowel sounds.

RESULTS: In this article, we report that single neurons in the left Vim encode individual vowel phonemes mainly during speech production but also during perception and imagery. They mainly use one of two encoding schemes: broad or sharp tuning, with a similar percentage of units each. Sinusoidal tuning has been demonstrated in almost half of the broadly tuned units. Patients with PD had a lower percentage of speech-related units in each aspect of speech (production, perception, and imagery), a significantly lower percentage of broadly tuned units, and significantly lower median firing rates during speech production and perception, but significantly higher rates during imagery, than patients with essential tremor.

CONCLUSION: The results suggest that the left Vim uses mixed encoding schemes for speech features. Our findings explain, at the single neuron level, why deep brain stimulation and radiofrequency lesioning of the left Vim are likely to cause speech side effects. Moreover, they may indicate that speech-related units in the left Vim of patients with PD may be degraded even in the subclinical phase.

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Use of differential stimulation of the nucleus accumbens and anterior limb of the internal capsule to improve outcomes of obsessive-compulsive disorder

J Neurosurg 139:1376–1385, 2023

Personalized stimulation is key to optimizing the outcomes of deep brain stimulation (DBS) for refractory obsessive-compulsive disorder (OCD). However, the contacts in a single conventional electrode cannot be programmed independently, which may affect the therapeutic efficacy of DBS for OCD. Therefore, a novel designed electrode and implantable pulse generator (IPG) that could achieve differential stimulation parameters for different contacts was implanted into the nucleus accumbens (NAc) and anterior limb of the internal capsule (ALIC) of a cohort of patients with OCD.

METHODS Thirteen consecutive patients underwent bilateral DBS of the NAc-ALIC between January 2016 and May 2021. Differential stimulation of the NAc-ALIC was applied at initial activation. Primary effectiveness was assessed on the basis of change in scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from baseline to 6-month follow-up. Full-response was defined as a 35% decrease in Y-BOCS score. Secondary effectiveness measures were the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The local field potential of bilateral NAcALIC was recorded in 4 patients who were reimplanted with a sensing IPG after battery depletion of the previous IPG.

RESULTS The Y-BOCS, HAMA, and HAMD scores decreased remarkably during the first 6 months of DBS. Ten of 13 patients were categorized as responders (76.9%). Differential stimulation of the NAc-ALIC was favorable to optimization of the stimulation parameters by increasing the parameter configurations. Power spectral density analysis revealed pronounced delta-alpha frequency activity in the NAc-ALIC. Phase-amplitude coupling of the NAc-ALIC showed that strong coupling is present between the phase of delta-theta and broadband gamma amplitude.

CONCLUSIONS These preliminary findings indicate that differential stimulation of the NAc-ALIC can improve the efficacy of DBS for OCD.

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Stereotactic robot‑assisted MRI‑guided laser interstitial thermal therapy thalamotomy for medically intractable Parkinson’s disease tremor

Acta Neurochirurgica (2023) 165:1453–1460

Medically intractable Parkinson’s disease (PD) tremor is a common difficult clinical situation with major impact on patient’s quality of life (QOL). Deep brain stimulation (DBS) is an effective therapy but is not an option for many patients. Less invasive lesional brain surgery procedures, such as thalamotomy, have proven to be effective in these indications. Here, we describe the technical nuances and advantages of stereotactic robot-assisted MRI-guided laser interstitial thermal therapy (MRIg-LITT) thalamotomy for medically intractable PD tremor.

Method We describe 2 patients with medically intractable PD tremor treated with stereotactic robot-assisted MRIg-LITT thalamotomy performed under general anesthesia with intraoperative electrophysiological testing. Pre and postoperative tremor scores were assessed using the Fahn-Tolosa-Marin tremor rating scale (TRS).

Results At 3-month follow-up, both patients demonstrated significant improvement in tremor symptoms subjectively and according to the TRS (75% for both). Patients also had substantial improvements in their QOL (32.54% and 38%) according to the 39-item PD questionnaire. Both patients underwent uncomplicated MRIg-LITT thalamotomy.

Conclusions In patients with medically intractable PD tremor who are unsuitable candidates for DBS, thalamotomy utilizing a stereotactic robot, intraoperative electrophysiological testing, and laser ablation with real-time MRI guidance may be a viable treatment option. However, further studies with larger sample sizes and longer follow-up periods are necessary to confirm these preliminary results.

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Dissociation of Broca’s area from Broca’s aphasia in patients undergoing neurosurgical resections

J Neurosurg 138:847–857, 2023

Broca’s aphasia is a syndrome of impaired fluency with retained comprehension. The authors used an unbiased algorithm to examine which neuroanatomical areas are most likely to result in Broca’s aphasia following surgical lesions.

METHODS Patients were prospectively evaluated with standardized language batteries before and after surgery. Broca’s area was defined anatomically as the pars opercularis and triangularis of the inferior frontal gyrus. Broca’s aphasia was defined by the Western Aphasia Battery language assessment. Resections were outlined from MRI scans to construct 3D volumes of interest. These were aligned using a nonlinear transformation to Montreal Neurological Institute brain space. A voxel-based lesion-symptom mapping (VLSM) algorithm was used to test for areas statistically associated with Broca’s aphasia when incorporated into a resection, as well as areas associated with deficits in fluency independent of Western Aphasia Battery classification. Postoperative MRI scans were reviewed in blinded fashion to estimate the percentage resection of Broca’s area compared to areas identified using the VLSM algorithm.

RESULTS A total of 289 patients had early language evaluations, of whom 19 had postoperative Broca’s aphasia. VLSM analysis revealed an area that was highly correlated (p < 0.001) with Broca’s aphasia, spanning ventral sensorimotor cortex and supramarginal gyri, as well as extending into subcortical white matter tracts. Reduced fluency scores were significantly associated with an overlapping region of interest. The fluency score was negatively correlated with fraction of resected precentral, postcentral, and supramarginal components of the VLSM area.

CONCLUSIONS Broca’s aphasia does not typically arise from neurosurgical resections in Broca’s area. When Broca’s aphasia does occur after surgery, it is typically in the early postoperative period, improves by 1 month, and is associated with resections of ventral sensorimotor cortex and supramarginal gyri.

 

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Nucleus accumbens: a systematic review of neural circuitry and clinical studies in healthy and pathological states

J Neurosurg 138:337–346, 2023

The nucleus accumbens (NAcc) of the ventral striatum is critically involved in goal- and reward-based behavior. Structural and functional abnormalities of the NAcc or its associated neural systems are involved in neurological and psychiatric disorders. Studies of neural circuitry have shed light on the subtleties of the structural and functional derangements of the NAcc across various diseases. In this systematic review, the authors sought to identify human studies involving the NAcc and provide a synthesis of the literature on the known circuity of the NAcc in healthy and diseased states, as well as the clinical outcomes following neuromodulation.

METHODS A systematic review was conducted using the PubMed, Embase, and Scopus databases. Neuroimaging studies that reported on neural circuitry related to the human NAcc with sample sizes greater than 5 patients were included. Demographic data, aim, design and duration, participants, and clinical and neurocircuitry details and outcomes of the studies were extracted.

RESULTS Of 3591 resultant articles, 123 were included. The NAcc and its corticolimbic connections to other brain regions, such as the prefrontal cortex, are largely involved in reward and pain processes, with distinct functional circuitry between the shell and core in healthy patients. There is heterogeneity between clinical studies with regard to the NAcc indirect targeting coordinates, methods for postoperative confirmation, and blinded trial design. Neuromodulation studies provided promising clinical results in the context of addiction and substance misuse, obsessive-compulsive disorder, and mood disorders. The most common complications were impaired memory or concentration, and a notable serious complication was hypomania.

CONCLUSIONS The functional diversity of the NAcc highlights the importance of studying the NAcc in healthy and pathological states. The results of this review suggest that NAcc neuromodulation has been attempted in the management of diverse psychiatric indications. There is promising, emerging evidence that the NAcc may be an effective target for specific reward- or pain-based pathologies with a reasonable risk profile.

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Long-Term Outcomes of Bilateral Subthalamic Nucleus Deep Brain Stimulation for Patients With Parkinson’s Disease: 10 Years and Beyond

Neurosurgery 91:726–733, 2022

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents an effective treatment for severe Parkinson’s disease (PD), but little is known about the long-term benefit.

OBJECTIVE: To investigate the survival rate and long-term outcome of DBS.

METHODS: We investigated all 81 patients including 37 males and 44 females who underwent bilateral STN DBS from March 2005 to March 2008 at a single institution. The current survival status of the patients was investigated. Preoperative and postoperative follow-up assessments were analyzed.

RESULTS: The mean age at the time of surgery was 62 (range 27-82) years, and the median clinical follow-up duration was 145 months. Thirty-five patients (43%) died during the follow-up period. The mean duration from DBS surgery to death was 110.46 ± 40.8 (range 0-155) months. The cumulative survival rate is as follows: 98.8 ± 1.2% (1 year), 95.1 ± 2.4% (5 years), and 79.0 ± 4.5% (10 years). Of the 81 patients, 33 (40%) were ambulatory up to more than 11 years. The Unified Parkinson’s Disease Rating Scale (UPDRS) score was significantly improved until 5 years after surgery although it showed a tendency to increase again after 10 years. The patient group with both electrodes located within the STN showed a higher rate of survival and maintained ambulation.

CONCLUSION: STN DBS is a safe and effective treatment for patients with advanced PD. This study based on the long-term follow-up of large patient populations can be used to elucidate the long-term fate of patients who underwent bilateral STN DBS for PD.

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A population-normalized tractographic fiber atlas of the anterior limb of the internal capsule: relevance to surgical neuromodulation

J Neurosurg 137:1278–1288, 2022

The anterior limb of the internal capsule (ALIC) is a white matter highway that connects several subcortical structures to the prefrontal cortex. Although surgical interventions in the ALIC have been used to treat a number of psychiatric illnesses, there is significant debate regarding what fibers are targeted for intervention. This debate is partially due to an incomplete understanding of connectivity in the region.

METHODS To better understand this complex structure, the authors employed a novel tractography-based approach to examine how fibers from the thalamus and subthalamic nucleus (STN) traverse the ALIC. Furthermore, the authors analyzed connections from the medial dorsal nucleus, anterior nucleus, and ventral anterior nucleus of the thalamus.

RESULTS The results showed that there is an organizational gradient of thalamic fibers medially and STN fibers laterally in the ALIC that fades more anteriorly. These findings, in combination with the known corticotopic organization described by previous studies, allow for a more thorough understanding of the organization of the white matter fibers in the ALIC.

CONCLUSIONS These results are important for understanding and targeting of neuromodulatory therapies in the ALIC and may help explain why differences in therapeutic effect are observed for different areas of the ALIC.

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