Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall of stimulus features and categories.

Objective: Here, we demonstrate the first successful use of static neural stimulation patterns for specific information content. These static patterns were derived by a model that was applied to a subject's own hippocampal spatiotemporal neural codes for memory. Approach: We constructed a new model of processes by which the hippocampus encodes specific memory items via spatiotemporal firing of neural ensembles that underlie the successful encoding of targeted content into short-term memory. A memory decoding model (MDM) of hippocampal CA3 and CA1 neural firing was computed which derives a stimulation pattern for CA1 and CA3 neurons to be applied during the encoding (sample) phase of a delayed match-to-sample (DMS) human short-term memory task. Main results: MDM electrical stimulation delivered to the CA1 and CA3 locations in the hippocampus during the sample phase of DMS trials facilitated memory of images from the DMS task during a delayed recognition (DR) task that also included control images that were not from the DMS task. Across all subjects, the stimulated trials exhibited significant changes in performance in 22.4% of patient and category combinations. Changes in performance were a combination of both increased memory performance and decreased memory performance, with increases in performance occurring at almost 2 to 1 relative to decreases in performance. Across patients with impaired memory that received bilateral stimulation, significant changes in over 37.9% of patient and category combinations was seen with the changes in memory performance show a ratio of increased to decreased performance of over 4 to 1. Modification of memory performance was dependent on whether memory function was intact or impaired, and if stimulation was applied bilaterally or unilaterally, with nearly all increase in performance seen in subjects with impaired memory receiving bilateral stimulation. Significance: These results demonstrate that memory encoding in patients with impaired memory function can be facilitated for specific memory content, which offers a stimulation method for a future implantable neural prosthetic to improve human memory.

No Delayed Ruptures on Long-Term Follow-Up of a Case Series of Persistently Filling Saccular Internal Carotid Artery Aneurysms After Flow Diversion With the Pipeline Embolization Device.

BACKGROUND AND OBJECTIVES: Flow diversion of intracranial aneurysms results in high occlusion rates. However, 10% to 20% remain persistently filling at 1 year. Often, these are retreated, but benefits of retreatment are not well established. A better understanding of the long-term rupture risk of persistently filling aneurysms after flow diversion is needed. METHODS: Our institutional database of 974 flow diversion cases was queried for persistently filling saccular aneurysms of the clinoidal, ophthalmic, and communicating segments of the internal carotid artery treated with the pipeline embolization device (PED, Medtronic). Persistent filling was defined as continued flow into the aneurysm on 1 year catheter angiogram. The clinical record was queried for retreatments and delayed ruptures. Clinical follow-up was required for at least 2 years. RESULTS: Ninety-four persistent aneurysms were identified. The average untreated aneurysm size was 5.6 mm. A branch vessel originated separately in 55% of cases from the body of the aneurysm in 10.6% of cases and from the neck in 34% of cases. Eighteen percent of aneurysms demonstrated >95% filling at 1 year, and 61% were filling 5% to 95% of their original size. The mean follow-up time was 4.9 years, including 41 cases with >5 years. No retreatment was undertaken in 91.5% of aneurysms. There were no cases of delayed subarachnoid hemorrhage. CONCLUSION: Among saccular internal carotid artery aneurysms treated with PED that demonstrated persistent aneurysm filling at 1 year, there were no instances of delayed rupture on long-term follow-up. These data suggest that observation may be appropriate for continued aneurysm filling at least in the first several years after PED placement.

A Case for Electron-Astrophysics.

The smallest characteristic scales, at which electron dynamics determines the plasma behaviour, are the next frontier in space and astrophysical plasma research. The analysis of astrophysical processes at these scales lies at the heart of the research theme of electron-astrophysics. Electron scales are the ultimate bottleneck for dissipation of plasma turbulence, which is a fundamental process not understood in the electron-kinetic regime. In addition, plasma electrons often play an important role for the spatial transfer of thermal energy due to the high heat flux associated with their velocity distribution. The regulation of this electron heat flux is likewise not understood. By focussing on these and other fundamental electron processes, the research theme of electron-astrophysics links outstanding science questions of great importance to the fields of space physics, astrophysics, and laboratory plasma physics. In this White Paper, submitted to ESA in response to the Voyage 2050 call, we review a selection of these outstanding questions, discuss their importance, and present a roadmap for answering them through novel space-mission concepts.

Determining the Bulk Parameters of Plasma Electrons from Pitch-Angle Distribution Measurements.

Electrostatic analysers measure the flux of plasma particles in velocity space and determine their velocity distribution function. There are occasions when science objectives require high time-resolution measurements, and the instrument operates in short measurement cycles, sampling only a portion of the velocity distribution function. One such high-resolution measurement strategy consists of sampling the two-dimensional pitch-angle distributions of the plasma particles, which describes the velocities of the particles with respect to the local magnetic field direction. Here, we investigate the accuracy of plasma bulk parameters from such high-resolution measurements. We simulate electron observations from the Solar Wind Analyser's (SWA) Electron Analyser System (EAS) on board Solar Orbiter. We show that fitting analysis of the synthetic datasets determines the plasma temperature and kappa index of the distribution within 10% of their actual values, even at large heliocentric distances where the expected solar wind flux is very low. Interestingly, we show that although measurement points with zero counts are not statistically significant, they provide information about the particle distribution function which becomes important when the particle flux is low. We also examine the convergence of the fitting algorithm for expected plasma conditions and discuss the sources of statistical and systematic uncertainties.

On the Determination of Kappa Distribution Functions from Space Plasma Observations.

The velocities of space plasma particles, often follow kappa distribution functions. The kappa index, which labels and governs these distributions, is an important parameter in understanding the plasma dynamics. Space science missions often carry plasma instruments on board which observe the plasma particles and construct their velocity distribution functions. A proper analysis of the velocity distribution functions derives the plasma bulk parameters, such as the plasma density, speed, temperature, and kappa index. Commonly, the plasma bulk density, velocity, and temperature are determined from the velocity moments of the observed distribution function. Interestingly, recent studies demonstrated the calculation of the kappa index from the speed (kinetic energy) moments of the distribution function. Such a novel calculation could be very useful in future analyses and applications. This study examines the accuracy of the specific method using synthetic plasma proton observations by a typical electrostatic analyzer. We analyze the modeled observations in order to derive the plasma bulk parameters, which we compare with the parameters we used to model the observations in the first place. Through this comparison, we quantify the systematic and statistical errors in the derived moments, and we discuss their possible sources.

Author Correction: Multicellular 3D Neurovascular Unit Model for Assessing Hypoxia and Neuroinflammation Induced Blood-Brain Barrier Dysfunction.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Community economic factors influence outcomes for patients with primary malignant glioma.

BACKGROUND: Community economics and other social health determinants influence outcomes in oncologic patient populations. We sought to explore their impact on presentation, treatment, and survival in glioma patients. METHODS: A retrospective cohort of patients with glioma (World Health Organization grades III-IV) diagnosed between 1999 and 2017 was assembled with data abstracted from medical record review. Patient factors included race, primary care provider (PCP) identified, marital status, insurance status, and employment status. Median household income based on zip code was used to classify patients as residing in high-income communities (HICs; ie, above the median state income) or low-income communities (LICs; ie, below the median state income). The Kaplan-Meier method was used to assess overall survival (OS); Cox proportional hazards regression was used to explore associations with OS. RESULTS: Included were 312 patients, 73% from LICs. Survivors residing in LICs and HICs did not differ by age, sex, race, tumor grade, having a PCP, employment status, insurance, time to presentation, or baseline performance status. Median OS was 4.1 months shorter for LIC patients (19.7 vs 15.6 mo; hazard ratio [HR], 0.75; 95% CI: 0.56-0.98, P = 0.04); this difference persisted with 1-year survival of 66% for HICs versus 61% for LICs at 1 year, 34% versus 24% at 3 years, and 29% versus 17% at 5 years. Multivariable analysis controlling for age, grade, and chemotherapy treatment showed a 25% lower risk of death for HIC patients (HR, 0.75; 95% CI: 0.57-0.99, P < 0.05). CONCLUSIONS: The economic status of a glioma patient's community may influence survival. Future efforts should investigate potential mechanisms such as health care access, stress, treatment adherence, and social support.

Hippocampal CA1 and CA3 neural recording in the human brain: validation of depth electrode placement through high-resolution imaging and electrophysiology.

OBJECTIVE: Intracranial human brain recordings typically utilize recording systems that do not distinguish individual neuron action potentials. In such cases, individual neurons are not identified by location within functional circuits. In this paper, verified localization of singly recorded hippocampal neurons within the CA3 and CA1 cell fields is demonstrated. METHODS: Macro-micro depth electrodes were implanted in 23 human patients undergoing invasive monitoring for identification of epileptic seizure foci. Individual neurons were isolated and identified via extracellular action potential waveforms recorded via macro-micro depth electrodes localized within the hippocampus. A morphometric survey was performed using 3T MRI scans of hippocampi from the 23 implanted patients, as well as 46 normal (i.e., nonepileptic) patients and 26 patients with a history of epilepsy but no history of depth electrode placement, which provided average dimensions of the hippocampus along typical implantation tracks. Localization within CA3 and CA1 cell fields was tentatively assigned on the basis of recording electrode site, stereotactic positioning of the depth electrode in comparison with the morphometric survey, and postsurgical MRI. Cells were selected as candidate CA3 and CA1 principal neurons on the basis of waveform and firing rate characteristics and confirmed within the CA3-to-CA1 neural projection pathways via measures of functional connectivity. RESULTS: Cross-correlation analysis confirmed that nearly 80% of putative CA3-to-CA1 cell pairs exhibited positive correlations compatible with feed-forward connection between the cells, while only 2.6% exhibited feedback (inverse) connectivity. Even though synchronous and long-latency correlations were excluded, feed-forward correlation between CA3-CA1 pairs was identified in 1071 (26%) of 4070 total pairs, which favorably compares to reports of 20%-25% feed-forward CA3-CA1 correlation noted in published animal studies. CONCLUSIONS: This study demonstrates the ability to record neurons in vivo from specified regions and subfields of the human brain. As brain-machine interface and neural prosthetic research continues to expand, it is necessary to be able to identify recording and stimulation sites within neural circuits of interest.

Multicellular 3D Neurovascular Unit Model for Assessing Hypoxia and Neuroinflammation Induced Blood-Brain Barrier Dysfunction.

The blood-brain barrier (BBB) is a dynamic component of the brain-vascular interface that maintains brain homeostasis and regulates solute permeability into brain tissue. The expression of tight junction proteins between adjacent endothelial cells and the presence of efflux proteins prevents entry of foreign substances into the brain parenchyma. BBB dysfunction, however, is evident in many neurological disorders including ischemic stroke, trauma, and chronic neurodegenerative diseases. Currently, major contributors to BBB dysfunction are not well understood. Here, we employed a multicellular 3D neurovascular unit organoid containing human brain microvascular endothelial cells, pericytes, astrocytes, microglia, oligodendrocytes and neurons to model the effects of hypoxia and neuroinflammation on BBB function. Organoids were cultured in hypoxic chamber with 0.1% O2 for 24 hours. Organoids cultured under this hypoxic condition showed increased permeability, pro-inflammatory cytokine production, and increased oxidative stress. The anti-inflammatory agents, secoisolariciresinol diglucoside and 2-arachidonoyl glycerol, demonstrated protection by reducing inflammatory cytokine levels in the organoids under hypoxic conditions. Through the assessment of a free radical scavenger and an anti-inflammatory endocannabinoid, we hereby report the utility of the model in drug development for drug candidates that may reduce the effects of ROS and inflammation under disease conditions. This 3D organoid model recapitulates characteristics of BBB dysfunction under hypoxic physiological conditions and when exposed to exogenous neuroinflammatory mediators and hence may have potential in disease modeling and therapeutic development.

Drug compound screening in single and integrated multi-organoid body-on-a-chip systems.

Current practices in drug development have led to therapeutic compounds being approved for widespread use in humans, only to be later withdrawn due to unanticipated toxicity. These occurrences are largely the result of erroneous data generated by in vivo and in vitro preclinical models that do not accurately recapitulate human physiology. Herein, a human primary cell- and stem cell-derived 3D organoid technology is employed to screen a panel of drugs that were recalled from market by the FDA. The platform is comprised of multiple tissue organoid types that remain viable for at least 28 days, in vitro. For many of these compounds, the 3D organoid system was able to demonstrate toxicity. Furthermore, organoids exposed to non-toxic compounds remained viable at clinically relevant doses. Additional experiments were performed on integrated multi-organoid systems containing liver, cardiac, lung, vascular, testis, colon, and brain. These integrated systems proved to maintain viability and expressed functional biomarkers, long-term. Examples are provided that demonstrate how multi-organoid 'body-on-a-chip' systems may be used to model the interdependent metabolism and downstream effects of drugs across multiple tissues in a single platform. Such 3D in vitro systems represent a more physiologically relevant model for drug screening and will likely reduce the cost and failure rate associated with the approval of new drugs.

Left Far Lateral Craniotomy for Clipping of a Posterior Inferior Cerebellar Artery Aneurysm.

Objectives The complex anatomical relationships of neurovascular structures at the craniovertebral junction make the clipping of a posterior inferior cerebellar artery (PICA) aneurysm surgically challenging. We demonstrate the clipping of a PICA aneurysm in the video. Design, Setting, and Participant A 65-year-old woman presented with a nonsymptomatic unruptured left PICA aneurysm; follow-up angiography showed an increase in its size. Preoperative angiography demonstrated a PICA aneurysm with the neck close to the origin of the PICA. A daughter sac of the aneurysm was also noted. A left far lateral approach was performed. The vagoaccessory triangle was exposed after opening the arachnoid membrane. The origin of the PICA and the aneurysm were revealed after exploration. The aneurysm neck was identified both proximally and distally. Two fenestrated clips were applied; subsequent indocyanine green (ICG) videoangiography demonstrated that the PICA was obstructed. One clip was adjusted, and repeated ICG videoangiography showed the PICA was patent. An endoscope was used before and after the clip application to better understand the anatomy of the aneurysm and inspect clip positions ( Fig. 1 ). Outcome The patient was neurologically intact postoperatively and was discharged on postoperative day 4. Conclusion PICA aneurysms require careful treatment. Impingement of adjacent structures can cause severe complications. Lower cranial nerve damage can cause dysphagia, and compromised vertebral/PICA circulation can cause brainstem symptoms, such as Wallenberg's syndrome. Intraoperative ICG videoangiography should be used to evaluate vessel patency, and the endoscope should be used to fully inspect the aneurysm and evaluate the clip application. The link to the video can be found at: https://youtu.be/dKxFQTRA89g .

Far Lateral Craniotomy for Resection of Foramen Magnum Meningioma.

Objective Foramen magnum meningiomas present a formidable challenge to resection due to frequent involvement of the lower cranial nerves and vertebrobasilar circulation. The video shows the use of a far lateral craniotomy to resect a foramen magnum meningioma. Design, Setting, and Participant A 49-year-old woman presented with neck pain and was found to have a large foramen magnum meningioma ( Fig. 1A, B ). Drilling of the posterior occipital condyle was required to gain access to the lateral aspect of the brain stem. The amount of occipital condyle resection varies by patient and pathology. Outcome/Result Maximal total resection of the tumor was achieved ( Fig. 1B, C ), and the patient was discharged on postoperative day 4 with no neurologic deficits. The technique for tumor microdissection ( Fig. 2 ) is shown in the video. Conclusion Given the close proximity of foramen magnum meningiomas to vital structures at the craniocervical junction, surgical resection with careful microdissection and preservation of the overlying dura to prevent postoperative pseudomeningocele is necessary to successfully manage this pathology in those patients who are surgical candidates. The link to the video can be found at: https://youtu.be/Mds9N1x2zE0 .

Surgical treatment of falcotentorial meningiomas: a retrospective review of a single-institution experience.

OBJECTIVE: Meningiomas at the falcotentorial junction represent a rare subgroup of complex meningiomas. Debate remains regarding the appropriate treatment strategy for and optimal surgical approach to these tumors, and surgical outcomes have not been well described in the literature. The authors reviewed their single-institution experience in the management, approach selection, and outcomes for patients with falcotentorial meningiomas. METHODS: From the medical records, the authors identified all patients with falcotentorial meningiomas treated with resection at the Barrow Neurological Institute between January 2007 and October 2017. Perioperative clinical, surgical, and radiographic data were retrospectively collected. For patients who underwent the supracerebellar infratentorial approach, the tentorial angle was defined as the angle between the line joining the nasion with the tuberculum sellae and the tentorium in the midsagittal plane. RESULTS: Falcotentorial meningiomas occurred in 0.97% (14/1441) of the patients with meningiomas. Most of the patients (13/14) were female, and the mean patient age was 59.8 ± 11.3 years. Of 17 total surgeries (20 procedures), 11 were single-stage primary surgeries, 3 were two-stage primary surgeries (6 procedures), 2 were reoperations for recurrence, and 1 was a reoperation after surgery had been aborted because of brain edema. Hydrocephalus was present in 5 of 17 cases, 4 of which required additional treatment. Various approaches were used, including the supracerebellar infratentorial (4/17), occipital transtentorial/transfalcine (4/17), anterior interhemispheric transsplenial (3/17), parietal transventricular (1/17), torcular (2/17), and staged supracerebellar infratentorial and occipital transtentorial/transfalcine (3/17) approaches. Of the 17 surgeries, 9 resulted in Simpson grade IV resection, and 3, 1, and 4 surgeries resulted in Simpson grades III, II, and I resection, respectively. The tentorial angle in cases with Simpson grade I resection was significantly smaller than in those with an unfavorable resection grade (43.3° ± 4.67° vs 54.0° ± 3.67°, p = 0.04). Complications occurred in 10 of 22 approaches (17 surgeries) and included visual field defects (6 cases, 2 permanent and 4 transient), hemiparesis (2 cases), hemidysesthesia (1 case), and cerebellar hematoma (1 case). CONCLUSIONS: Falcotentorial meningiomas are challenging lesions. A steep tentorial angle is an unfavorable preoperative radiographic factor for achieving maximal resection with the supracerebellar infratentorial approach. Collectively, the study findings show that versatility is required to treat patients with falcotentorial meningiomas and that treatment goals and surgical approach must be individualized to obtain optimal surgical results.

Mini-pterional approach for clip ligation of ethmoidal dural arteriovenous fistula.

Ethmoidal dural arteriovenous fistulas (DAVFs) have a near-universal association with cortical venous drainage and a malignant clinical course. Endovascular treatment options are often limited due to the high frequency of ophthalmic artery ethmoidal supply. A 64-year-old gentleman presented with syncope and was found to have a right ethmoidal DAVF. Rather than the traditional bicoronal craniotomy, an endoscope-assisted mini-pterional approach for clip ligation is demonstrated. The mini-pterional craniotomy allows a minimally invasive approach to ethmoidal DAVF via a lateral trajectory. The endoscope can help achieve full visualization in the narrow corridor.The video can be found here: https://youtu.be/ZroXp-T35DI.

Two cases of brainstem neurocysticercosis removal: operative video.

Neurocysticercosis is primarily managed with anthelminthic, antiepileptic, and corticosteroid therapies. Surgical removal of the larval cyst is indicated when associated mass effect causes neurological symptoms, as demonstrated in two cases. Cyst resection was achieved via the far lateral approach for a cervicomedullary cyst in one patient and via the subtemporal approach for a mesencephalic cyst in another. The cyst wall should be kept intact, when possible, to avoid dissemination of the inflammation-evoking contents. As the contents are usually semisolid and can be removed via suction, it is not necessary to remove the gliotic capsule or adherent portions of the cyst wall in highly eloquent locations. The video can be found here: https://youtu.be/GqbaJu5sy1o.

Insular cavernous malformation resection through a minipterional, transsylvian approach.

Cavernous malformations of the brain are low-flow vascular lesions that have a propensity to hemorrhage. Extensive surgical approaches are often required for operative cure of deep-seated lesions. A 23-year-old female presented with a cavernous malformation of the left posterior insula with surrounding hematoma measuring up to 3 cm. A minimally invasive (mini-)pterional craniotomy with a transsylvian approach was selected. Endoscopic assistance was utilized to confirm complete resection of the lesion. The minipterional craniotomy is a minimally invasive approach that provides optimal exposure for sylvian fissure dissection and resection of many temporal and insular lesions. The video can be found here: https://youtu.be/9z6_EhU6lxs.

Corpus callosotomy via laser interstitial thermal therapy: a case series.

Corpus callosotomy has been used as a form of surgical palliation for patients suffering from medically refractory generalized seizures, including drop attacks. Callosotomy has traditionally been described as involving a craniotomy with microdissection. MR-guided laser interstitial thermal therapy (MRg-LITT) has recently been used as a minimally invasive method for performing surgical ablation of epileptogenic foci and corpus callosotomy. The authors present 3 cases in which MRg-LITT was used to perform a corpus callosotomy as part of a staged surgical procedure for a patient with multiple seizure types and in instances when further ablation of residual corpus callosum is necessary after a prior open surgical procedure. To the authors' knowledge, this is the first case series of corpus callosotomy performed using the MRg-LITT system with a 3.3-year average follow-up. Although MRg-LITT is not expected to replace the traditional corpus callosotomy in all cases, it is a safe, effective, and durable alternative to the traditional open corpus callosotomy, particularly in the setting of a prior craniotomy.

Candidate Performance and Observable Audience Response: Laughter and Applause-Cheering During the First 2016 Clinton-Trump Presidential Debate.

Raucous audience applause-cheering, laughter, and even booing by a passionately involved electorate marked the 2016 presidential debates from the start of the primary season. While the presence and intensity of these observable audience responses (OARs) can be expected from partisan primary debates, the amount of not just laughter, but also applause-cheering and booing during the first general election debate between Hillary Clinton and Donald Trump was unprecedented. Such norm-violating audience behavior raises questions concerning not just the presence, strength, and timing of these OAR, but also their influence on those watching on television, streaming video, or listening to radio. This report presents findings from three interconnected studies. Study 1 provides a baseline for analysis by systematically coding the studio audience response in terms of utterance type (laughter, applause-cheering, booing, and mixtures), when and how intensely it occurred, and in response to which candidate. Study 2 uses observational analysis of 362 undergraduate students at a large state university in the southern United States who watched the debate on seven different news networks in separate rooms and evaluated the candidates' performance. Study 2 considered co-occurrence of OAR in the studio audience and in the field study rooms, finding laughter predominated and was more likely to co-occur than other OAR types. When standardized cumulative strength of room OAR was compared, findings suggest co-occurring OAR was stronger than that occurring solely in the field study rooms. Analysis of truncated data allowing for consideration of studio audience OAR intensity found that OAR intensity was not related to OAR type occurring in the field study rooms, but had a small effect on standardized cumulative strength. Study 3 considers the results of a continuous response measure (CRM) dial study in which 34 West Texas community members watched and rated the candidates during the first debate. Findings suggest that applause-cheering significantly influenced liking of the speaking candidate, whereas laughter did not. Further, response to applause-cheering was mediated by party identity, although not for laughter. Conclusions from these studies suggest laughter as being more stereotypic and likely to be mimicked whereas applause-cheering may be more socially contagious.

Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall.

OBJECTIVE: We demonstrate here the first successful implementation in humans of a proof-of-concept system for restoring and improving memory function via facilitation of memory encoding using the patient's own hippocampal spatiotemporal neural codes for memory. Memory in humans is subject to disruption by drugs, disease and brain injury, yet previous attempts to restore or rescue memory function in humans typically involved only nonspecific, modulation of brain areas and neural systems related to memory retrieval. APPROACH: We have constructed a model of processes by which the hippocampus encodes memory items via spatiotemporal firing of neural ensembles that underlie the successful encoding of short-term memory. A nonlinear multi-input, multi-output (MIMO) model of hippocampal CA3 and CA1 neural firing is computed that predicts activation patterns of CA1 neurons during the encoding (sample) phase of a delayed match-to-sample (DMS) human short-term memory task. MAIN RESULTS: MIMO model-derived electrical stimulation delivered to the same CA1 locations during the sample phase of DMS trials facilitated short-term/working memory by 37% during the task. Longer term memory retention was also tested in the same human subjects with a delayed recognition (DR) task that utilized images from the DMS task, along with images that were not from the task. Across the subjects, the stimulated trials exhibited significant improvement (35%) in both short-term and long-term retention of visual information. SIGNIFICANCE: These results demonstrate the facilitation of memory encoding which is an important feature for the construction of an implantable neural prosthetic to improve human memory.

Laser Interstitial Thermal Therapy for Mesial Temporal Lobe Epilepsy.

Approximately one-third of patients with epilepsy do not achieve adequate seizure control through medical management alone. Mesial temporal lobe epilepsy (MTLE) is one of the most common forms of medically refractory epilepsy referred for surgical management. Stereotactic laser amygdalohippocampotomy using magnetic resonance-guided laser interstitial thermal therapy (MRg-LITT) is an important emerging therapy for MTLE. Initial published reports support MRg-LITT as a less invasive surgical option with a shorter hospital stay and fewer neurocognitive side effects compared with craniotomy for anterior temporal lobectomy with amygdalohippocampectomy and selective amygdalohippocampectomy. We provide a historical overview of laser interstitial thermal therapy development and the technological advancements that led to the currently available commercial systems. Current applications of MRg-LITT for MTLE, reported outcomes, and technical issues of the surgical procedure are reviewed. Although initial reports indicate that stereotactic laser amygdalohippocampotomy may be a safe and effective therapy for medically refractory MTLE, further research is required to establish its long-term effectiveness and its cost/benefit profile. ABBREVIATIONS: ATLAH, anterior temporal lobectomy with amygdalohippocampectomyLITT, laser interstitial thermal therapyMRg-LITT, magnetic resonance-guided laser interstitial thermal therapyMTLE, mesial temporal lobe epilepsySAH, selective amygdalohippocampectomySLAH, stereotactic laser amygdalohippocampotomy.