Lesions to both somatic and affective pain pathways lead to decreased salience network connectivity.

Human pain is a salient stimulus composed of two main components: a sensory/somatic component, carrying peripheral nociceptive sensation via the spinothalamic tract and brainstem nuclei to the thalamus and then to sensory cortical regions, and an affective (suffering) component, where information from central thalamic nuclei is carried to the anterior insula, dorsal anterior cingulate cortex and other regions. While the sensory component processes information about stimulus location and intensity, the affective component processes information regarding pain-related expectations, motivation to reduce pain and pain unpleasantness. Unlike investigations of acute pain that are based on the introduction of real-time stimulus during brain recordings, chronic pain investigations are usually based on longitudinal and case-control studies, which are limited in their ability to infer the functional network topology of chronic pain. In the current study, we utilized the unique opportunity to target the CNS's pain pathways in two different hierarchical locations to establish causality between pain relief and specific connectivity changes seen within the salience and sensorimotor networks. We examined how lesions to the affective and somatic pain pathways affect resting-state network topology in cancer patients suffering from severe intractable pain. Two procedures have been employed: percutaneous cervical cordotomy (n = 15), hypothesized to disrupt the transmission of the sensory component of pain along the spinothalamic tract, or stereotactic cingulotomy (n = 7), which refers to bilateral intracranial ablation of an area in the dorsal anterior cingulate cortex and is known to ameliorate the affective component of pain. Both procedures led to immediate significant alleviation of experienced pain and decreased functional connectivity within the salience network. However, only the sensory procedure (cordotomy) led to decreased connectivity within the sensorimotor network. Thus, our results support the existence of two converging systems relaying experienced pain, showing that pain-related suffering can be either directly influenced by interfering with the affective pathway or indirectly influenced by interfering with the ascending spinothalamic tract.

Laser interstitial thermal therapy (LITT) for pediatric low-grade glioma-case presentations and lessons learned.

BACKGROUND: The surgical treatment of brain tumors has developed over time, offering customized strategies for patients and their specific lesions. One of the most recent advances in pediatric neuro-oncological surgery is laser interstitial thermal therapy (LITT). However, its effectiveness and indications are still being evaluated. The aim of this work is to review the current literature on LITT for pediatric low-grade gliomas (pLGG) and evaluate our initial results in this context. METHODS: We retrospectively reviewed our pediatric neurosurgery database for patients who received LITT treatment between November 2019 and December 2023. We collected data on the indications for LITT, technical issues during the procedure, and clinical and radiological follow-up. RESULTS: Three patients underwent 5 LITT procedures for pLGG. The lesion was thalamo-peduncular in one patient, cingulate in one, and deep parietal in one patient. Two patients had a previous open resection done and were diagnosed with pLGG. One patient underwent a stereotaxic biopsy during the LITT procedure that was non-diagnostic. The same patient underwent a later open resection of the tumor in the cingulate gyrus. There were no surgical complications and all patients were discharged home on the first post-operative day. The follow-up period was between 20 and 40 months. Radiological follow-up showed a progressive reduction of the tumor in patients with LGG. CONCLUSION: Laser interstitial thermal therapy is a minimally invasive treatment that shows promise in treating deep-seated pLGG in children. The treatment has demonstrated a reduction in tumor volume, and the positive results continue over time. LITT can be used as an alternative treatment for tumors located in areas that are difficult to access surgically or in cases where other standard treatment options have failed.

Anesthesia-induced loss of consciousness disrupts auditory responses beyond primary cortex.

Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial electroencephalogram (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.

[LASER INTERSTITIAL THERMAL THERAPY (LITT) IN NEUROSURGERY].

INTRODUCTION: Laser interstitial thermal therapy (LITT) has emerged as a new treatment option for various conditions within the neurosurgery world, not only due to its minimal invasiveness but also because it has been shown to be safe and effective. Combined with magnetic resonance thermography, LITT gives surgeons the ability to estimate damage in real time and precisely ablate the target tissue while minimizing thermal damage to adjacent structures. In recent years, LITT has become a reality in epilepsy surgery and in neuro-oncology and is emerging as an option in other fields in neurosurgery.

[EPILEPSY SURGERY IN CHILDREN: A SUMMARY OF A DECADE AT THE SOURASKY TEL AVIV MEDICAL CENTER].

INTRODUCTION: Drug-resistant epilepsy in children is associated with morbidity, developmental regression and mortality. Over recent years, there is an increase in awareness regarding the role of surgery in the treatment of refractory epilepsy, both in the diagnostic phase and for treatment, reducing the number and magnitude of seizures. Technological advancements have enabled a minimalization of surgery, with reduction in surgical associated morbidity. METHODS: In this retrospective study, we review our experience with cranial surgery for epilepsy between the years 2011-2020. Collected data included information regarding the epileptic disorder, surgery, surgical-related complications and epilepsy outcome. RESULTS: A total of 93 children underwent 110 cranial surgeries over a decade. The main etiologies included cortical dysplasia (29), Rasmussen encephalitis (10), genetic disorders (9), tumors (7) and tuberous sclerosis (7). The main surgeries included lobectomies (32), focal resections (26), hemispherotomies (25), and callosotomies (16). Two children underwent MRI-guided laser interstitial thermal treatment (LITT). The most significant improvements following surgery were following hemispherotomy or tumor resection (100% of children, each). Following resections for cortical dysplasia led to a significant improvement in 70%. In 83% of children undergoing callosotomy, there were no additional drop seizures; 14% of the entire group underwent additional epilepsy surgery; 23% of children had an unexpected complication, in the vast majority with no permanent sequela. There was not mortality. CONCLUSIONS: Epilepsy surgery may lead to significant improvement and even cure of epilepsy. There is a wide span of epilepsy surgical procedures. Ealy referral of children with refractory epilepsy for surgical evaluation may significantly reduce the developmental injury, and improve functional outcomes.

Asleep DBS under ketamine sedation: Proof of concept.

BACKGROUND: Deep brain stimulation (DBS) is commonly and safely performed for selective Parkinson's disease patients. Many centers perform DBS lead positioning exclusively under local anesthesia, to optimize brain microelectrode recordings (MER) and testing of stimulation-related therapeutic and side effects. These measures enable physiological identification of the DBS borders and subdomains based on electrophysiological properties like firing rates and patterns, intra-operative evaluation of therapeutic window, and improvement of lead placement accuracy. Nevertheless, due to the challenges of awake surgery, some centers use sedation or general anesthesia, despite the distortion of discharge properties and interference with clinical testing, resulting in potential impact on surgical outcomes. Thus, there is a need for a novel anesthesia regimen that enables sedation without compromising intra-operative monitoring. OBJECTIVE: This open-label study investigates the use of low-dose ketamine for conscious sedation during microelectrode recordings and lead positioning in subthalamic nucleus (STN) DBS for Parkinson's disease patients. METHODS: Three anesthetic regimens were retrospectively compared in 38 surgeries (74 MER trajectories, 5962 recording sites) across three DBS centers: 1) Interleaved propofol-ketamine (PK), 2) Interleaved propofol-awake (PA), and 3) Fully awake (AA). RESULTS: All anesthesia regimens achieved satisfactory MER. Detection of STN borders and subdomains by expert electrophysiologist was similar between the groups. Electrophysiological signature of the STN under ketamine was not inferior to either control group. All patients completed stimulation testing. CONCLUSIONS: This study supports a low-dose ketamine anesthesia regimen for DBS which allows microelectrode recordings and stimulation testing that are not inferior to those conducted under awake and propofol-awake regimens and may optimize patient experience. A prospective double-blind study that would also compare patients' satisfaction level and clinical outcome should be performed to confirm these findings.

Adopting MR-guided stereotactic laser ablations for epileptic lesions: initial clinical experience and lessons learned.

OBJECTIVE: MR-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive technique for ablating brain lesions under real-time MRI feedback and control of the ablation process. The Medtronic Visualase system was recently approved for use in Europe and Israel. We report our initial technical experience using the system in the first 16 cases in which the system was used to ablate focal epileptogenic lesions. METHODS: We included all consecutive patients with intractable epilepsy who underwent MRgLITT procedures between 2018 and 2020. We reviewed medical charts and imaging studies of patients. Post-ablation MRIs were used to calculate ablation volumes. RESULTS: Seventeen MRgLITT procedures were performed in 16 patients. One cooling catheter/laser fiber assemblies were placed per patient. Indications for surgery were intractable epilepsy due to TLE (n = 7), suspected low-grade glioma (n = 4), radiological cortical dysplasia (n = 1), hypothalamic hamartoma (n = 1), and MR-negative foci (n = 3). Ablations were made using 30 to 70% of the maximal energy of the Visualase system. We used serial ablations as needed along the tract of the catheter by pulling back the optic fiber; the length of the lesion ranged between 7.4 and 38.1 mm. Ablation volume ranged between 0.27 and 6.78 mm3. Immediate post-ablation MRI demonstrated good ablation of the epileptic lesion in 16/17 cases. In one case with mesial temporal sclerosis, no ablation was performed due to suboptimal position of the catheter. That patient was successfully reoperated at a later date. Mean follow-up was 14.9 months (± 11.6 months). Eleven patients had follow-up longer than 12 months. Good seizure control (Engel I, A) was achieved in 7/11 patients (63%) and 1/11 (9%) had significant improvement in seizure frequency (Angle IIIa). Three patients (27%) did not experience improvement in their seizure frequency (Engel IV, B), and one of these patients died during the follow-up period from sudden unexpected death of epilepsy (SUDEP). No immediate or delayed neurological complications were documented in any of the cases during the follow-up period. CONCLUSIONS: MRgLITT is a promising technique and can be used safely as an alternative to open resection in both lesional and non-lesional intractable epilepsy cases. In our local series, the success rate of epilepsy surgery was comparable to recent publications.

Conflict monitoring mechanism at the single-neuron level in the human ventral anterior cingulate cortex.

Life requires monitoring and adjusting behavior in the face of conflicts. The conflict monitoring theory implicates the anterior cingulate cortex (ACC) in these processes; its ventral aspect (vACC) specializes in emotional conflict. To elucidate the underpinning neural mechanism, we recorded vACC extracellular activity from 12 patients with mood disorders or epilepsy who performed the face-emotional Stroop task. Behaviorally, both conflict detection and adaptation to conflict were evident. The firing rate of neurons in the vACC represented current conflict, i.e., current-congruency. The late onset of the effect is compatible with a role in monitoring. Additionally, early responses of some neurons represented the immediate history of conflicts, i.e., previous-trial-congruency. Finally, in some neurons the response to the current-trial was modulated by previous-trial-congruency, laying the ground for adjusting-to-conflicts. Our results uncover a single neuron level mechanism in the vACC that encodes and integrates past and present emotional conflicts, allowing humans to accommodate their responses accordingly.

Neurocognitive evaluation of brain metastases patients treated with post-resection stereotactic radiosurgery: a prospective single arm clinical trial.

PURPOSE: Post-operative radiation therapy for brain metastases (BM) has become standard treatment. Concerns regarding the deleterious cognitive effects of Whole Brain Radiation Therapy spurred a trend to use focal therapies such as stereotactic radiosurgery (SRS). The purpose of this study was to prospectively evaluate the neuropsychological effects following post-resection SRS treatment since limited data exist in this context. METHODS: We conducted a prospective single arm cohort study of patients with 1-2 BM, who underwent resection of a single BM between May 2015 to December 2016. Patients were evaluated for cognitive functions (NeuroTrax computerized neuropsychological battery; Modiin, Israel) and quality of life (QOL; QLQ-30, QLQ-BN20) before and 3 months following post-resection SRS. RESULTS: Twelve out of 14 patients completed pre- and post-SRS neurocognitive assessments. Overall, we did not detect significant neurocognitive or QOL changes 3 months following SRS. In a subgroup analysis among patients younger than 60 years, median global cognitive score increased from a pre-treatment score of 88 (72-102) to 95 (79-108), 3 months following SRS treatment, p = 0.042; Wilcoxon paired non-parametric test. Immediate verbal memory and executive functions scores increased from 86 (72-98) to 98 (92-112) and 86 (60-101) to 100 (80-126), respectively, p = 0.043. No significant cognitive changes were discovered among patients at the age of 60 or older. CONCLUSIONS: Post-resection radiosurgery has a safe neuro-cognitive profile and is associated with preservation of nearly all quality of life parameters. Patients younger than 60 years benefit most and may even regain some cognitive functions within a few months after treatment.

Combined treatment approach to cerebral arteriovenous malformation in pediatric patients: stereotactic radiosurgery to partially Onyx-embolized AVM.

PURPOSE: Treatment of cerebral arteriovenous malformations (AVM)-the most common cause of stroke in the pediatric population-can be challenging due to the complexity of size, morphology, and location. There is a significant risk in comparison to AVM treatment among adults. Thus, AVM treatment in the pediatric population imposes unique challenges. Recent improvements include optimized catheter techniques and better embolization materials, such as Onyx, a non-adhesive liquid embolic agent used in the adult population. These improvements have increased the success rate of total and near-total obliteration of cerebral AVM. However, the use of Onyx causes significant distortion of the MR and CT images, which must be accounted for in any radiation treatment planning predicated on CT and MRI. These image distortions impact on the actual delivered dose to the nidus and behoove heterogeneity correction. Our group has previously shared a solution for heterogeneity correction in the adult population. The purpose of this study is to show our experience in this unique group of pediatric patients. METHODS: This is a retrospective review of pediatric patients, who were undergoing combined endovascular embolization followed by SRS. The cohort consists of 14 patients undergoing SRS treatment in our institute between November 2006 and December 2012 with a mean follow-up of 49.9 months. Within this cohort, we retrospectively reviewed 12 consecutive pediatric patients who underwent a combined endovascular and SRS approach with a mean follow-up of 52.1 months and two patients receiving SRS-only treatment were excluded. RESULTS: In our cohort of 14 patients, 7 (50%) were male, with a mean age of 17.3 years (12.0-22.9) at the time of radiosurgery treatment. Mean age of beginning the combined modality treatment was 15.3 years (8.4-20). The median time from diagnosis to SRS was 24.3 months (11.1-64.4 months) in the complete cohort and 25.6 months (11.1-64.4) in the multimodality group. The overall median follow-up period was 49.9 months (range 12.8-118.8 months) in the complete cohort and 52.1 months (range 12.8-118.8 months) in the multimodality group. Eleven (78.6%) patients had at least one episode of hemorrhage prior to treatment. Spezler-Martin grades at baseline ranged from 2 to 5 (mean 3.2). Fifty percent had grade IV and V. Patients underwent a median of 2 (range 1-5) embolization procedures. The radiosurgical treatment dose to the margin of the angiography-based nidus: median prescription dose of 21.49 Gy (14.39-27.51) with a median max dose of 27.77 Gy (18.93-32.52). The median treatment volume was 0.6 cm3 (0.1-7.3 cm3). The Onyx embolization reduced the nidus target volume by a median of 66.7% (12.0-92.7%). We confirmed 10/14 (71%) complete closures. In 2/14 (14.2%) additional patients, a significant flow reduction was noted. In 1/14 (7.1%) patients, no significant change was noted during the observation period and two (14.2%) patients were without follow-up information. In two patients, post-treatment edema was noted; however, none was clinically significant and resolved without additional intervention or treatment. CONCLUSIONS: This cohort comprises the largest combined Onyx-SRS pediatric experience in the literature. In conjunction with our adult group study, we show that the use of Onyx reduces the SRS treatment target volume significantly. Importantly, we implemented the heterogeneity correction to avoid increased radiation exposure to normal surrounding brain tissue. The combined approach appears to be safe provided that the above-mentioned corrections are implemented.

[NEUROSURGICAL INTERVENTIONS FOR INTRACTABLE ONCOLOGICAL PAIN].

INTRODUCTION: Pain is one of the most common symptoms among cancer patients, and particularly in those who suffer from metastatic or terminal disease. There is great importance in delivering good pain management to these patients in order to alleviate their suffering, improve their functional status and their overall quality of life. In most cases, pain management is based on pharmacotherapy with opioids and other medications. However, there are selected patients for whom pharmacotherapy does not achieve acceptable pain relief or is associated with marked side effects. These patients, who suffer from refractory cancer pain, may benefit from neurosurgical procedures selectively intervening in different locations along the pain signaling pathways. This article summarizes several of these neurosurgical procedures: percutaneous cordotomy for unilateral pain, punctuate midline myelotomy for visceral pain and stereotactic cingulotomy for diffuse pain syndromes. This article demonstrates the use of careful patient selection by an interdisciplinary team which is critical for the success of these procedures. The team consists of palliative care specialists, pain specialists and a neurosurgeon. These neurosurgical interventions are presented through representative clinical cases, followed by a discussion of the clinical considerations that guided the choice of the therapeutic approach for each case.

O-Arm-Guided Percutaneous Radiofrequency Cordotomy.

BACKGROUND: Pain is often one of the most debilitating symptoms in patients with advanced oncological disease. Patients with localized pain due to malignancy refractory to medical treatment can benefit from selective percutaneous cordotomy that disconnects the ascending pain fibers in the spinothalamic tract. OBJECTIVES: Over the past year, we have been performing percutaneous radiofrequency cordotomy with the use of the O-Arm intraoperative imaging system that allows both 2D fluoroscopy and 3D reconstructed computerized tomography imaging. We present our experience using this technique, focusing on technical nuances and complications. METHODS: A retrospective analysis was conducted of all patients who underwent percutaneous cordotomy between March 2016 and March 2017. RESULTS: Nineteen patients underwent percutaneous cordotomy procedures. Two patients developed intraoperative delirium and were unable to tolerate the procedure. In 16 out of 17 completed procedures, we achieved excellent immediate pain relief (94%). At 1 month after operation, 15 of the 17 (88%) patients were pain free, and at 3 months 5 out of 5 patients available for follow-up were still free of their original pain. Mirror pain developed in 6 of the 17 patients (35%), but was mild in 4 of these cases and controlled with medications. We experienced 1 serious complication (6%) of ipsilateral hemiparesis. CONCLUSION: Percutaneous cordotomy using the O-Arm is safe and effective in the treatment of intractable oncological pain.

Double Anterior Stereotactic Cingulotomy for Intractable Oncological Pain.

BACKGROUND: Stereotactic anterior cingulotomy has been used in the treatment of patients suffering from refractory oncological pain due to its effects on pain perception. However, the optimal targets as well as suitable candidates and outcome measures have not been well defined. We report our initial experience in the ablation of 2 cingulotomy targets on each side and the use of the Brief Pain Inventory (BPI) as a perioperative assessment tool. METHODS: A retrospective review of all patients who underwent stereotactic anterior cingulotomy in our Department between November 2015 and February 2017 was performed. All patients had advanced metastatic cancer with limited prognosis and suffered from intractable oncological pain. RESULTS: Thirteen patients (10 women and 3 men) underwent 14 cingulotomy procedures. Their mean age was 54 ± 14 years. All patients reported substantial pain relief immediately after the operation. Out of the 6 preoperatively bedridden patients, 3 started ambulating shortly after. At the 1-month follow-up, the mean preoperative Visual Analogue Scale score decreased from 9 ± 0.9 to 4 ± 2.7 (p = 0.003). Mean BPI pain severity and interference scores decreased from levels of 29 ± 4 and 55 ± 12 to 16 ± 12 (p = 0.028) and 37 ± 15 (p = 0.043), respectively. During the 1- and 3-month follow-up visits, 9/11 patients (82%) and 5/7 patients (71%) available for follow-up reported substantial pain relief. No patient reported worsening of pain during the study period. Neuropsychological analyses of 6 patients showed stable cognitive functions with a mild nonsignificant decline in focused attention and executive functions. Adverse events included transient confusion or mild apathy in 5 patients (38%) lasting 1-4 weeks. CONCLUSIONS: Our initial experience indicates that double stereotactic cingulotomy is safe and effective in alleviating refractory oncological pain.

Spinal Dural Arteriovenous Fistula: A Review.

Spinal dural arteriovenous fistula (SDAVF) is a rare disease, the etiology of which is not entirely clear. It is the most common vascular malformation of the spinal cord, comprising 60-80 % of the cases. The clinical presentation and imaging findings may be nonspecific and misleading, often mistaking it for other entities like demyelinating or degenerative diseases of the spine.This chapter describes the imaging findings, clinical signs, and symptoms of this disease and also the available treatment options according to the current literature.Angiography is still considered the gold standard for diagnosis; however, MRI/MRA is increasingly used as a screening tool. Modern endovascular techniques are becoming increasingly more effective in treating SDAVF offering a less invasive treatment option; however, they still lag behind surgical success rates which approach 100 %. The outcome of both treatment options is similar if complete obliteration of the fistula is obtained and depends mainly on the severity of neurological dysfunction before treatment.Heightened awareness by radiologists and clinicians to this rare entity is essential to make a timely diagnosis of this treatable disease. A multidisciplinary treatment approach is required in order to make appropriate treatment decisions.

Silk flow diverter in the treatment of complex intracranial aneurysms: a single-center experience with 60 patients.

BACKGROUND: Flow diverters are used to treat complex aneurysms that are not amenable to coiling. The aim of the present work was to retrospectively evaluate our experience with the Silk flow diverter. Technical nuances and complications are specifically discussed. METHODS: Retrospectively data was collected on patients treated with Silk between October 2008 and October 2013. RESULTS: Sixty patients harboring 67 aneurysms were treated using the Silk. Fifteen aneurysms were located in the posterior circulation and 52 in the anterior. A good angiographic result was achieved in 88 % (53/60) of the aneurysms available for imaging follow-up. There were ten treatment-related complications, 80 % were ischemic. Risk of complications increased with aneurysm size and in aneurysms of the posterior circulation. CONCLUSIONS: Silk flow diverters are a good treatment option for aneurysms of the anterior circulation. Additional stents may be required in specific cases due to the Silk's low radial resistance. Treatment of giant fusiform aneurysms of the posterior circulation with Silk flow diverters is associated with a high rate of severe complications.

Younger age predicts greater effectiveness of spinal cord stimulation for chronic pain.

BACKGROUND: Spinal cord stimulation (SCS) is an accepted surgical treatment for neuropathic pain in failed back syndrome or complex regional pain syndrome. However, even in the best selected surgical cases the predictors of adequate pain control are not well defined. The aim of this study was to identify predictors of outcome in patients who underwent SCS in our center. METHODS: We performed a retrospective analysis of our neurosurgical database for patients who underwent SCS over the last 8 years in an attempt to identify factors predictive of outcome. RESULTS: Forty-one patients underwent implantation of epidural electrodes, 34 patients had a successful stimulation trial and received permanent devices. Nine patients experienced a late failure at a median time of 7.8 months (range, 4.5-19 months) after implantation. Age was significantly associated with outcome. Younger patients had a significantly lower rate of treatment failure, and none of the patients above 65 years had a successful long-term outcome. CONCLUSIONS: Our results suggest that younger age is associated with greater long-term effectiveness of spinal cord stimulation and therefore age may influence the success of SCS therapy with older patients having a greater tendency to failure. Earlier intervention may be beneficial in these chronic pain patients.

Age-related changes in diffusion tensor imaging metrics of fornix subregions in healthy humans.

OBJECTIVE: White matter diffusivity measures of the fornix change with aging, which likely relates to changes in memory and cognition in older adults. Subregional variations in forniceal diffusivity may exist, given its heterogeneous anatomy and connectivity; however, these have not been closely examined in vivo. We examined diffusivity parameters (fractional anisotropy, FA; radial diffusivity, RD; axial diffusivity, AD) in forniceal subregions of healthy subjects and correlated them with age and hippocampal volume. METHODS: Diffusion-weighted imaging and streamline tractography of the fornix were performed on 20 healthy, right-handed females (23-66 years). Six anatomical subregions were defined: midline (body, column, precommissural fornix) or lateral (fimbria, crura, postcommissural fornix). Regression analysis was performed comparing diffusivities against age. Hippocampal and ventricular volumes were also compared. RESULTS: Diffusivity values revealed statistical changes with age in both midline and lateralized subregions. The fornix body and left crus showed age-related alterations in all metrics (FA, RD, AD), whereas only right crus FA was altered. There was no significant change in hippocampal volumes, suggesting that forniceal changes may precede hippocampal age-related changes. CONCLUSIONS: Age-related changes in fornix diffusivity measures appear subregion dependent and asymmetrical. Specific subregion diffusivity measures may be a more sensitive aging marker than hippocampal volume change.

Clinical aspects of ballistic peripheral nerve injury: shrapnel versus gunshot.

OBJECTIVES: Ballistic injuries to peripheral nerves pose special challenges in terms of indications, timing and type of surgical intervention. The aim of the present work was to analyze our experience in the surgical treatment of peripheral nerve ballistic injuries with respect to the mechanism of injury (gunshot versus shrapnel), and identify common and dissimilar prognostic factors in both types of injury. METHODS: This study was conducted on 42 patients totaling 58 nerves. Twenty-two patients (32 nerves) were injured by gunshot and 20 patients (26 nerves) by shrapnel. Median postoperative follow-up was 33 months (range 12 months to 14 years). RESULTS: Overall postoperative outcome appears to be more favorable for gunshot-wound (GSW) patients than shrapnel-injured patients, especially in terms of neuropathic pain relief (75 % vs. 58 % respectively, p < 0.05). Presence of foreign particles in shrapnel injured patients has a negative impact on the surgical outcome in terms of rate of pain improvement (28 % compared to 67 % in patients with and without foreign particles, respectively). Nerve graft reconstruction, rather than neurolysis, seems to be the more beneficial treatment for shrapnel-induced neuropathic pain (100 % vs. 47 % in improvement rate, respectively). Early surgical intervention (median 2 months after injury) significantly relieved neuropathic pain in 83 % of shrapnel-injured patients compared to 58 % in patients operated later. CONCLUSIONS: This study suggests that shrapnel injury is more destructive for nerve tissue than gunshot injury. Our impression is that early surgical intervention in shrapnel injuries and split nerve grafting (especially when small fragments are recognized in the nerve) significantly improve the patient's functional activity and quality of life.

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

BACKGROUND AND OBJECTIVES: 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.

Machine learning decoding of single neurons in the thalamus for speech brain-machine interfaces.

Objective. Our goal is to decode firing patterns of single neurons in the left ventralis intermediate nucleus (Vim) of the thalamus, related to speech production, perception, and imagery. For realistic speech brain-machine interfaces (BMIs), we aim to characterize the amount of thalamic neurons necessary for high accuracy decoding.Approach. We intraoperatively recorded single neuron activity in the left Vim of eight neurosurgical patients undergoing implantation of deep brain stimulator or RF lesioning during production, perception and imagery of the five monophthongal vowel sounds. We utilized the Spade decoder, a machine learning algorithm that dynamically learns specific features of firing patterns and is based on sparse decomposition of the high dimensional feature space.Main results. Spade outperformed all algorithms compared with, for all three aspects of speech: production, perception and imagery, and obtained accuracies of 100%, 96%, and 92%, respectively (chance level: 20%) based on pooling together neurons across all patients. The accuracy was logarithmic in the amount of neurons for all three aspects of speech. Regardless of the amount of units employed, production gained highest accuracies, whereas perception and imagery equated with each other.Significance. Our research renders single neuron activity in the left Vim a promising source of inputs to BMIs for restoration of speech faculties for locked-in patients or patients with anarthria or dysarthria to allow them to communicate again. Our characterization of how many neurons are necessary to achieve a certain decoding accuracy is of utmost importance for planning BMI implantation.