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.

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.

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.

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.

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.


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.

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.

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.

Radiological identification of the globus pallidus motor subregion in Parkinson’s disease

J Neurosurg 137:175–183, 2022

Globus pallidus (GP) lesioning improves motor symptoms of Parkinson’s disease (PD) and is occasionally associated with nonmotor side effects. Although these variable clinical effects were shown to be site-specific within the GP, the motor and nonmotor subregions have not been distinguished radiologically in patients with PD. The GP was recently found to have a distinct radiological signature on diffusion MRI (dMRI), potentially related to its unique cellular content and organization (or tissue architecture). In this study, the authors hypothesize that the magnitude of water diffusivity, a surrogate for tissue architecture, will radiologically distinguish motor from nonmotor GP subregions in patients with PD. They also hypothesize that the therapeutic focused ultrasound pallidotomy lesions will preferentially overlap the motor subregion.

METHODS Diffusion MRI from healthy subjects (n = 45, test-retest S1200 cohort) and PD patients (n = 33) was parcellated based on the magnitude of water diffusivity in the GP, as measured orientation distribution function (ODF). A clustering algorithm was used to identify GP parcels with distinct ODF magnitude. The individual parcels were used as seeds for tractography to distinguish motor from nonmotor subregions. The locations of focused ultrasound lesions relative to the GP parcels were also analyzed in 11 patients with PD.

RESULTS Radiologically, three distinct parcels were identified within the GP in healthy controls and PD patients: posterior, central, and anterior. The posterior and central parcels comprised the motor subregion and the anterior parcel was classified as a nonmotor subregion based on their tractography connections. The focused ultrasound lesions preferentially overlapped with the motor subregion (posterior more than central). The hotspots for motor improvement were localized in the posterior GP parcel.

CONCLUSIONS Using a data-driven approach of ODF-based parcellation, the authors radiologically distinguished GP motor subregions in patients with PD. This method can aid stereotactic targeting in patients with PD undergoing surgical treatments, especially focused ultrasound ablation.

Tractography-Based Surgical Targeting for Thalamic Deep Brain Stimulation: A Comparison of Probabilistic vs Deterministic Fiber Tracking of the Dentato-Rubro-Thalamic Tract

Neurosurgery 90:419–425, 2022

The ventral intermediate (VIM) thalamic nucleus is the main target for the surgical treatment of refractory tremor. Initial targeting traditionally relies on atlas-based stereotactic targeting formulas, which only minimally account for individual anatomy. Al- ternative approaches have been proposed, including direct targeting of the dentato-rubro- thalamic tract (DRTT), which, in clinical settings, is generally reconstructed with deterministic tracking. Whether more advanced probabilistic techniques are feasible on clinical-grade magnetic resonance acquisitions and lead to enhanced reconstructions is poorly understood.

OBJECTIVE: To compare DRTT reconstructed with deterministic vs probabilistic tracking. METHODS: Thisisaretrospectivestudyof19patientswithessentialtremorwhounderwentdeep brain stimulation (DBS) with intraoperative neurophysiology and stimulation testing. We assessed the proximity of the DRTT to the DBS lead and to the active contact chosen based on clinical response.

RESULTS: In the commissural plane, the deterministic DRTT was anterior (P<104)and  < 104) to the DBS lead. By contrast, although the probabilistic DRTT was also anterior to the lead (P < 104), there was no difference in the mediolateral dimension (P = .5). Moreover, the 3- dimensional Euclidean distance from the active contact to the probabilistic DRTT was smaller vs the distance to the deterministic DRTT (3.32 ± 1.70 mm vs 5.01 ± 2.12 mm; P < 104).

CONCLUSION: DRTT reconstructed with probabilistic fiber tracking was superior in spatial proximity to the physiology-guided DBS lead and to the empirically chosen active contact. These data inform strategies for surgical targeting of the VIM.

Direct targeting of the ventral intermediate nucleus of the thalamus in deep brain stimulation for essential tremor

J Neurosurg 136:662–671, 2022

The ventral intermediate nucleus of the thalamus (VIM) is an effective target for deep brain stimulation (DBS) to control symptoms related to essential tremor. The VIM is typically targeted using indirect methods, although studies have reported visualization of the VIM on proton density–weighted MRI. This study compares the outcomes between patients who underwent VIM DBS with direct and indirect targeting.

METHODS Between August 2013 and December 2019, 230 patients underwent VIM DBS at the senior author’s institution. Of these patients, 92 had direct targeting (direct visualization on proton density 3-T MRI). The remaining 138 patients had indirect targeting (relative to the third ventricle and anterior commissure–posterior commissure line).

RESULTS Coordinates of electrodes placed with direct targeting were significantly more lateral (p < 0.001) and anterior (p < 0.001) than those placed with indirect targeting. The optimal stimulation amplitude for devices measured in voltage was lower for those who underwent direct targeting than for those who underwent indirect targeting (p < 0.001). Patients undergoing direct targeting had a greater improvement only in their Quality of Life in Essential Tremor Questionnaire hobby score versus those undergoing indirect targeting (p = 0.04). The direct targeting group had substantially more symptomatic hemorrhages than the indirect targeting group (p = 0.04). All patients who experienced a postoperative hemorrhage after DBS recovered without intervention.

CONCLUSIONS Patients who underwent direct VIM targeting for DBS treatment of essential tremor had similar clinical outcomes to those who underwent indirect targeting. Direct VIM targeting is safe and effective.

Distinct approaches to language pathway tractography

J Neurosurg 136:589–600, 2022

Visualization of subcortical language pathways by means of diffusion tensor imaging–fiber tracking (DTIFT) is evolving as an important tool for surgical planning and decision making in patients with language-suspect brain tumors. Repetitive navigated transcranial magnetic stimulation (rTMS) cortical language mapping noninvasively provides additional functional information. Efforts to incorporate rTMS data into DTI-FT are promising, but the lack of established protocols makes it hard to assess clinical utility. The authors performed DTI-FT of important language pathways by using five distinct approaches in an effort to evaluate the respective clinical usefulness of each approach.

METHODS Thirty patients with left-hemispheric perisylvian lesions underwent preoperative rTMS language mapping and DTI. FT of the principal language tracts was conducted according to different strategies: Ia, anatomical landmark based; Ib, lesion-focused landmark based; IIa, rTMS based; IIb, rTMS based with postprocessing; and III, rTMS enhanced (based on a combination of structural and functional data). The authors analyzed the respective success of each method in revealing streamlines and conducted a multinational survey with expert clinicians to evaluate aspects of clinical utility.

RESULTS The authors observed high usefulness and accuracy ratings for anatomy-based approaches (Ia and Ib). Postprocessing of rTMS-based tractograms (IIb) led to more balanced perceived information content but did not improve the usefulness for surgical planning and risk assessment. Landmark-based tractography (Ia and Ib) was most successful in delineating major language tracts (98% success), whereas rTMS-based tractography (IIa and IIb) frequently failed to reveal streamlines and provided less complete tractograms than the landmark-based approach (p < 0.001). The lesionfocused landmark-based (Ib) and the rTMS-enhanced (III) approaches were the most preferred methods.

CONCLUSIONS The lesion-focused landmark-based approach (Ib) achieved the best ratings and enabled visualization of the principal language tracts in almost all cases. The rTMS-enhanced approach (III) was positively evaluated by the experts because it can reveal cortico-subcortical connections, but the functional relevance of these connections is still unclear. The use of regions of interest derived solely from cortical rTMS mapping (IIa and IIb) leads to cluttered images that are of limited use in clinical practice.

Brain Structural Changes in Carpal Tunnel Syndrome Patients

Neurosurgery 89:978–986, 2021

Carpal tunnel syndrome (CTS) is a common peripheral entrapment neuropathy. However, CTS-related changes of brain structural covariance and structural covariance networks (SCNs) patterns have not been clearly studied. OBJECTIVE: To explore CTS-related brain changes from perspectives of structural connectivity and SCNs.

METHODS: Brain structural magnetic resonance images were acquired from 27 CTS patients and 19 healthy controls (HCs). Structural covariance and SCNs were constructed based on gray matter volume. The global network properties including clustering coefficient (Cp), characteristic path length (Lp), small-worldness index, global efficiency (Eglob), and local efficiency (Eloc) and regional network properties including degree, betweenness centrality (BC), and Eloc of a given node were calculated with graph theoretical analysis.

RESULTS: Compared with HCs, the strength of structural connectivity between the dorsal anterior insula and medial prefrontal thalamus decreased (P < .001) in CTS patients. There was no intergroup difference of area under the curve for Cp, Lp¸Eglob, and Eloc (all P>.05). The real-world SCN of CTS patients showed a small-world topology ranging from 2% to 32%. CTS patients showed lower nodal degrees of the dorsal anterior insula and medial prefrontal thalamus, and higher Eloc of a given node and BC in the lateral occipital cortex (P < .001) and the dorsolateral middle temporal gyrus (P < .001) than HCs, respectively.

CONCLUSION: CTS had a profound impact on brain structures from perspectives of structural connectivity and SCNs.

Central Nervous System Plasticity Influences Language and Cognitive Recovery in Adult Glioma

Neurosurgery 89:539–548, 2021

Gliomas exist within the framework of complex neuronal circuitry in which network dynamics influence both tumor biology and cognition. The generalized impairment of cognition or loss of language function is a common occurrence for glioma patients.

The interface between intrinsic brain tumors such as gliomas and functional cognitive networks are poorly understood. The ability to communicate effectively is critically important for receiving oncological therapies and maintaining a high quality of life.

Although the propensity of gliomas to infiltrate cortical and subcortical structures and disrupt key anatomic language pathways is well documented, there is new evidence offering insight into the network and cellular mechanisms underpinning glioma-related aphasia and aphasia recovery.

In this review, we will outline the current understanding of the mechanisms of cognitive dysfunction and recovery, using aphasia as an illustrative model.

Fields of Forel Brain Stimulation Improves Levodopa-Unresponsive Gait and Balance Disorders in Parkinson’s Disease

Neurosurgery 89:450–459, 2021

Gait and balance disturbance are challenging symptoms in advanced Parkinson’s disease (PD). Anatomic and clinical data suggest that the fields of Forel may be a potential surgical target to treat these symptoms.

OBJECTIVE: To test whether bilateral stimulation centered at the fields of Forel improves levodopa unresponsive freezing of gait (FOG), balance problems, postural instability, and falls in PD.

METHODS: A total of 13 patients with levodopa-unresponsive gait disturbance (Hoehn and Yahr stage ≥3) were included. Patients were evaluated before (on-medication condition) and 1 yr after surgery (on-medication-on-stimulation condition). Motor symptoms and quality of life were assessed with the Unified Parkinson’s Disease Rating scale (UPDRS III) and Quality of Life scale (PDQ-39). Clinical and instrumented analyses assessed gait, balance, postural instability, and falls.

RESULTS: Surgery improved balance by 43% (95% confidence interval [CI]: 21.2-36.4 to 35.2-47.1; P = .0012), reduced FOG by 35% (95% CI: 15.1-20.3 to 8.1-15.3; P = .0021), and the monthly number of falls by 82.2% (95% CI: 2.2-6.9 to −0.2-1.7; P = .0039). Anticipatory postural adjustments, velocity to turn, and postural sway measurements also improved 1 yr after deep brain stimulation (DBS). UPDRS III motor scores were reduced by 27.2% postoperatively (95% CI: 42.6-54.3 to 30.2-40.5; P < .0001). Quality of life improved 27.5% (95% CI: 34.6-48.8 to 22.4-37.9; P = .0100).

CONCLUSION: Our results suggest that DBS of the fields of Forel improved motor symptoms in PD, as well as the FOG, falls, balance, postural instability, and quality of life.

Stereotactic posterior midline approach under direct microscopic view for biopsy of medulla oblongata tumors: technical considerations

Acta Neurochirurgica (2021) 163:1965–1968

Open and stereotactic transfrontal or transcerebellar approaches have been used to biopsy brainstem lesions.

Method In this report, a stereotactic posterior and midline approach to the distal medulla oblongata under microscopic view is described. The potential advantages and limitations are discussed, especially bilateral damage of the X nerve nuclei.

Conclusion This approach should be considered for biopsy of distal and posterior lesions. We strongly recommend the use of direct microscopic view to identify the medullary vessels, confirm the midline entry point, and avoid potential shift of the medulla. Further experience is needed to confirm safety and success rate of this approach.

Neurostimulation for treatment-resistant posttraumatic stress disorder

J Neurosurg 134:1715–1723, 2021

Posttraumatic stress disorder (PTSD) is a widespread and often devastating psychiatric condition. Core symptoms include intrusive and distressing thoughts, heightened reactivity, mood changes, cognitive impairments, and consequent avoidance of trauma-related stimuli. Symptoms of PTSD are often refractory to standard treatments, and neuromodulatory techniques have therefore drawn significant interest among the most treatment-resistant patients.

Transcranial magnetic stimulation has demonstrated minimal efficacy, and deep brain stimulation trials are currently ongoing.

PTSD is a disorder of neural circuitry; the current understanding includes involvement of the amygdala (basolateral and central nuclei), the prefrontal cortex (ventral medial and dorsolateral regions), and the hippocampus. Neuroimaging and optogenetic studies have improved the understanding of large-scale neural networks and the effects of microcircuitry manipulation, respectively.

This review discusses the current PTSD literature and ongoing neurostimulation trials, and it highlights the current understanding of neuronal circuit dysfunction in PTSD. The authors emphasize the anatomical correlations of PTSD’s hallmark symptoms, offer another potential deep brain stimulation target for PTSD, and note the need for continued research to identify useful biomarkers for the development of closed-loop therapies. Although there is hope that neuromodulation will become a viable treatment modality for PTSD, this concept remains theoretical, and further research should involve institutional review board–approved controlled prospective clinical studies.


Magnetic Resonance Imaging-Guided Laser Thermal Ventral Capsulotomy for Intractable Obsessive-Compulsive Disorder

Neurosurgery 88:1128–1135, 2021

Obsessive-compulsive disorder (OCD) is a disabling condition characterized by intrusive thoughts and repetitive behaviors. A subset of individuals have severe, treatment-resistant illness and are nonresponsive to medication or behavioral therapies. Without response to conventional therapeutic options, surgical intervention becomes an appropriate consideration.

OBJECTIVE: To report clinical outcomes and the safety profile of bilateral ventral anterior capsulotomy for OCD using magnetic resonance (MR)-guided laser interstitial thermal therapy (LITT) in 10 patients followed for 6 to 24 mo.

METHODS: A total of 10 patients underwent LITT for severe OCD; 1 patient withdrew prior to follow-up. LITT is a minimally invasive ablative technique performed with precise targeting and use of thermography under MR guidance. Lesions of the ventral anterior limb of the internal capsule by other techniques have been shown to be efficacious in prior studies.

RESULTS: A total of 7 of the 9 patients were considered full responders (77.8%; Yale- Brown Obsessive-Compulsive Scale change ≥35%). Adverse effects included transient apathy/amotivation postsurgery (2 patients). One patient had a small tract hemorrhage where the laser fiber traversed the cerebral cortex as well as persistent insomnia postsurgery. One individual died after a drug overdose 7 mo postsurgery, which was judged unrelated to the surgery.

CONCLUSION: LITT ventral capsulotomy was generally well tolerated, with promising evidence of effectiveness in the largest such series to date. Results were comparable to those after gamma knife ventral capsulotomy, as well as ventral anterior limb deep brain stimulation.


Electrocorticography During Deep Brain Stimulation Surgery

Neurosurgery 88:E420–E426, 2021

Intraoperative research during deep brain stimulation (DBS) surgery has enabled major advances in understanding movement disorders pathophysiology and potential mechanisms for therapeutic benefit. In particular, over the last decade, recording electrocorticography (ECoG) from the cortical surface, simultaneously with subcortical recordings, has become an important research tool for assessing basal gangliathalamocortical circuit physiology.

OBJECTIVE: To provide confirmation of the safety of performing ECoG duringDBS surgery, using data fromcenters involved in 2 BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative-funded basic human neuroscience projects. METHODS: Datawere collected separately at 4 centers. The primary endpoint was complication rate, defined as any intraoperative event, infection, or postoperative magnetic resonance imaging abnormality requiring clinical follow-up. Complication rates for explanatory variables were compared using point biserial correlations and Fisher exact tests.

RESULTS: A total of 367 DBS surgeries involving ECoG were reviewed. No cortical hemorrhages were observed. Seven complications occurred: 4 intraparenchymal hemorrhages and 3 infections (complication rate of 1.91%; CI=0.77%-3.89%). The placement of 2 separate ECoG research electrodes through a single burr hole (84 cases) did not result in a significantly different rate of complications, compared to placement of a single electrode (3.6% vs 1.5%; P = .4). Research data were obtained successfully in 350 surgeries (95.4%).

CONCLUSION: Combined with the single report previously available, which described no ECoG-related complications in a single-center cohort of 200 cases, these findings suggest that research ECOG during DBS surgery did not significantly alter complication rates.

Brain connectomics applied to oncological neuroscience: from a traditional surgical strategy focusing on glioma topography to a meta-network approach

Acta Neurochirurgica (2021) 163:905–917

The classical way for surgical selection and planning in cerebral glioma mainly focused on tumor topography. The emerging science of connectomics, which aims of mapping brain connectivity, resulted in a paradigmatic shift from a modular account of cerebral organization to a meta-network perspective. Adaptive behavior is actually mediated by constant changes in interactions within and across large-scale delocalized neural systems underlying conation, cognition, and emotion.

Here, to optimize the onco-functional balance of glioma surgery, the purpose is to switch toward a connectome-based resection taking account of both relationships between the tumor and critical distributed circuits (especially subcortical pathways) as well as the perpetual instability of the meta-network. Such dynamic in the neural spatiotemporal integration permits functional reallocation leading to neurological recovery after massive resection in structures traditionally thought as “inoperable.” This better understanding of connectome increases benefit/risk ratio of surgery (i) by selecting resection in areas deemed “eloquent” according to a localizationist dogma; (ii), conversely, by refining intraoperative awake cognitive mapping and monitoring in so-called non-eloquent areas; (iii) by improving preoperative information, enabling an optimal selection of intrasurgical tasks tailored to the patient’s wishes; (iv) by developing an “oncological disconnection surgery”; (v) by defining a personalized multistep surgical strategy adapted to individual brain reshaping potential; and (vi) ultimately by preserving environmentally and socially appropriate behavior, including return to work, while increasing the extent of (possibly repeated) resection(s).

Such a holistic vision of neural processing can enhance reliability of connectomal surgery in oncological neuroscience and may also be applied to restorative neurosurgery.