Magnetic resonance-guided focused ultrasound in the treatment of refractory essential tremor: a systematic review and meta-analysis.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging treatment for medication-refractory essential tremor (ET). The objective of this study was to evaluate long-term (up to 5 years) safety and efficacy of unilateral MRgFUS in the treatment of ET. METHODS: The authors performed a systematic search through 4 databases to find relevant clinical studies. Binary outcomes were analyzed and reported as odds ratios and 95% confidence intervals, while continuous outcomes were analyzed and reported as standardized mean differences (SMDs) and 95% confidence intervals. Furthermore, a univariable meta-regression was performed to evaluate the association between various covariates and the outcomes including the mean difference in the Clinical Rating Scale for Tremor (CRST) score and hand tremor scores. Sensitivity analysis was performed to address any heterogeneity. RESULTS: A total of 43 studies comprising 1818 patients with ET who underwent MRgFUS were identified. Of the 1539 patients with data on sex, 1095 (71.2%) were male. The mean follow-up duration ranged from 3 months to 8.4 years among the studies. The mean total CRST score significantly decreased at 3, 6, and 12 months post-MRgFUS (SMD -4.5, p = 0.0069; SMD -4.9, p = 0.0045; and SMD -2.95, p = 0.0039, respectively). The mean hand tremor scores significantly mitigated at 3, 6, 12, 24, and 36 months post-MRgFUS (SMD -3.99, p = 0.05; SMD -4.5, p = 0.05; SMD -1.99, p < 0.0001; SMD - 2.07, p = 0.0002; and SMD -2.1, p < 0.0001, respectively). Furthermore, the mean Quality of Life in Essential Tremor Questionnaire scores were improved at 3 months (SMD -2.8, p = 0.0025), 6 months (SMD -4.1, p = 0.04), 12 months (SMD -1.57, p = 0.0004), 2 years (SMD -1.64, p = 0.0003), and 3 years (SMD -1.14, p = 0.08). Our meta-regression findings showed that sex (p = 0.03), unlike age, handedness, symptom duration, and peak energy levels at 3 months, was associated with a significantly higher mean difference in tremor severity. CONCLUSIONS: This meta-analysis provides strong evidence supporting the efficacy and safety of unilateral MRgFUS for the treatment of ET in terms of tremor severity and quality of life with acceptable adverse events.

Differential cortical layer engagement during seizure initiation and spread in humans.

Despite decades of research, we still do not understand how spontaneous human seizures start and spread - especially at the level of neuronal microcircuits. In this study, we used laminar arrays of micro-electrodes to simultaneously record the local field potentials and multi-unit neural activities across the six layers of the neocortex during focal seizures in humans. We found that, within the ictal onset zone, the discharges generated during a seizure consisted of current sinks and sources only within the infra-granular and granular layers. Outside of the seizure onset zone, ictal discharges reflected current flow in the supra-granular layers. Interestingly, these patterns of current flow evolved during the course of the seizure - especially outside the seizure onset zone where superficial sinks and sources extended into the deeper layers. Based on these observations, a framework describing cortical-cortical dynamics of seizures is proposed with implications for seizure localization, surgical targeting, and neuromodulation techniques to block the generation and propagation of seizures.

Aberrant fast spiking interneuronal activity precedes seizure transitions in humans.

There is active debate regarding how GABAergic function changes during seizure initiation and propagation, and whether interneuronal activity drives or impedes the pathophysiology. Here, we track cell-type specific firing during spontaneous human seizures to identify neocortical mechanisms of inhibitory failure. Fast-spiking interneuron activity was maximal over 1 second before equivalent excitatory increases, and showed transitions to out-of-phase firing prior to local tissue becoming incorporated into the seizure-driving territory. Using computational modeling, we linked this observation to transient saturation block as a precursor to seizure invasion, as supported by multiple lines of evidence in the patient data. We propose that transient blocking of inhibitory firing due to selective fast-spiking interneuron saturation-resulting from intense excitatory synaptic drive-is a novel mechanism that contributes to inhibitory failure, allowing seizure propagation.

A pharmacological and toxicological biochemical study of cardiovascular regulatory effects of hibiscus, corn silk, marjoram, and chamomile.

Hypertension is one of the most typical causes of morbidity and mortality. The present study investigated the possible antihypertensive cardiovascular effects of an herbal mixture extract of Hibiscus, Corn silk, Marjoram, and Chamomile. HPLC analysis of the water extract prepared from the aerial parts of four plants and their mixture was done to detect the most predominant compounds. A safety study was done prior to the efficacy study to determine the dose and ensure the extract's safety in female rats. Hypertension was induced in ovariectomized and non-ovariectomized rats by oral administration of 50 mg/kg of LName for 30 days; the hypertensive rats were classified into non-ovariectomized and ovariectomized untreated groups, treated groups with high and low doses of the mixture(150,300 mg/kg) given to ovariectomized and non-ovariectomized hypertensive groups and a standard group treated with angiotensin-converting enzyme inhibitor. The untreated group showed significant elevation of blood pressure, heart rate, cholesterol, triglycerides, malondialdehyde, cyclic adenosine monophosphate, angiotensin-converting enzyme, C-reactive protein, and significantly lowered reduced glutathione, high-density lipoprotein, and endothelial nitric oxide synthase. Treatment significantly counteracted the effects of L Name. The mixture provides a promising natural cardiovascular regulating supplement owing to its high contents of flavonoids.

Steam catalytic cracking and lump kinetics of naphtha to light olefins over nanocrystalline ZSM-5 zeolite.

This study investigates the reaction pathways and kinetics to comprehend the catalytic cracking of dodecane, a heavy naphtha model compound, over the nanocrystalline ZSM-5 catalyst in the presence and absence of steam with the aim of increasing olefin production. The nanocrystalline zeolite was characterized using XRD and BET, and the surface acidity was measured by NH3-TPD and Py-FTIR. The steam treated ZSM-5 contributed to an increase in pore volume with extra-framework alumina, resulting in highly catalytic active sites and hence higher olefin selectivity. The high conversion of dodecane (>90%) was achieved during catalytic cracking in the presence and absence of steam. In the presence of steam, the short pores of nano ZSM-5 led to an increase in the naphtha-to-olefin conversion with lesser dry gas and coke formation. The activation energies of primary cracking in the presence and absence of steam were slightly different. Lower activation energies through secondary cracking routes and higher reaction rate constants were obtained via assisted-steam catalytic cracking, promoted the selectivity towards light olefin products. Meanwhile the hydrogenation and alkylation reactions toward LPG and C5+ were favored in the absence of steam. Moreover, the ZSM-5 nano zeolite pores promoted more ß-scission reactions, resulting in higher selectivity towards ethylene and dry gas.

The mathematical catalyst deactivation models: a mini review.

Catalyst deactivation is a complex phenomenon and identifying an appropriate deactivation model is a key effort in the catalytic industry and plays a significant role in catalyst design. Accurate determination of the catalyst deactivation model is essential for optimizing the catalytic process. Different mechanisms of catalyst deactivation by coke and metal deposition lead to different deactivation models for catalyst activity decay. In the rigorous mathematical models of the reactors, the reaction kinetics were coupled with the deactivation kinetic equation to evaluate the product distribution with respect to conversion time. Finally, selective and nonselective deactivation kinetic models were designed to identify catalyst deactivation through the propagation of heterogeneous chemical reactions. Therefore, the present review discusses the catalyst deactivation models designed for CO2 hydrogenation, Fischer-Tropsch, biofuels and fossil fuels, which can facilitate the efforts to better represent the catalyst activities in various catalytic systems.

Characterizing brain dynamics during ketamine-induced dissociation and subsequent interactions with propofol using human intracranial neurophysiology.

Ketamine produces antidepressant effects in patients with treatment-resistant depression, but its usefulness is limited by its psychotropic side effects. Ketamine is thought to act via NMDA receptors and HCN1 channels to produce brain oscillations that are related to these effects. Using human intracranial recordings, we found that ketamine produces gamma oscillations in prefrontal cortex and hippocampus, structures previously implicated in ketamine's antidepressant effects, and a 3 Hz oscillation in posteromedial cortex, previously proposed as a mechanism for its dissociative effects. We analyzed oscillatory changes after subsequent propofol administration, whose GABAergic activity antagonizes ketamine's NMDA-mediated disinhibition, alongside a shared HCN1 inhibitory effect, to identify dynamics attributable to NMDA-mediated disinhibition versus HCN1 inhibition. Our results suggest that ketamine engages different neural circuits in distinct frequency-dependent patterns of activity to produce its antidepressant and dissociative sensory effects. These insights may help guide the development of brain dynamic biomarkers and novel therapeutics for depression.

Propofol disrupts alpha dynamics in functionally distinct thalamocortical networks during loss of consciousness.

During propofol-induced general anesthesia, alpha rhythms measured using electroencephalography undergo a striking shift from posterior to anterior, termed anteriorization, where the ubiquitous waking alpha is lost and a frontal alpha emerges. The functional significance of alpha anteriorization and the precise brain regions contributing to the phenomenon are a mystery. While posterior alpha is thought to be generated by thalamocortical circuits connecting nuclei of the sensory thalamus with their cortical partners, the thalamic origins of the propofol-induced alpha remain poorly understood. Here, we used human intracranial recordings to identify regions in sensory cortices where propofol attenuates a coherent alpha network, distinct from those in the frontal cortex where it amplifies coherent alpha and beta activities. We then performed diffusion tractography between these identified regions and individual thalamic nuclei to show that the opposing dynamics of anteriorization occur within two distinct thalamocortical networks. We found that propofol disrupted a posterior alpha network structurally connected with nuclei in the sensory and sensory associational regions of the thalamus. At the same time, propofol induced a coherent alpha oscillation within prefrontal cortical areas that were connected with thalamic nuclei involved in cognition, such as the mediodorsal nucleus. The cortical and thalamic anatomy involved, as well as their known functional roles, suggests multiple means by which propofol dismantles sensory and cognitive processes to achieve loss of consciousness.

Spatiotemporal spike-centered averaging reveals symmetry of temporal and spatial components of the spike-LFP relationship during human focal seizures.

The electrographic manifestation of neural activity can reflect the relationship between the faster action potentials of individual neurons and the slower fluctuations of the local field potential (LFP). This relationship is typically examined in the temporal domain using the spike-triggered average. In this study, we add a spatial component to this relationship. Here we first derive a theoretical model of the spike-LFP relationship across a macroelectrode. This mathematical derivation showed a special symmetry in the spike-LFP relationship wherein a sinc function in the temporal domain predicts a sinc function in the spatial domain. We show that this theoretical result is observed in a real-world system by characterizing the spike-LFP relationship using microelectrode array (MEA) recordings of human focal seizures. To do this, we present a approach, termed the spatiotemporal spike-centered average (st-SCA), that allows for visualization of the spike-LFP relationship in both the temporal and spatial domains. We applied this method to 25 MEA recordings obtained from seven patients with pharmacoresistant focal epilepsy. Of the five patients with MEAs implanted in recruited territory, three exhibited spatiotemporal patterns consistent with a sinc function, and two exhibited spatiotemporal patterns resembling deep wells of excitation. These results suggest that in some cases characterization of the spike-LFP relationship in the temporal domain is sufficient to predict the underlying spatial pattern. Finally, we discuss the biological interpretation of these findings and propose that the sinc function may reflect the role of mid-range excitatory connections during seizure activity.

Interim Safety Profile From the Feasibility Study of the BrainGate Neural Interface System.

BACKGROUND AND OBJECTIVES: Brain-computer interfaces (BCIs) are being developed to restore mobility, communication, and functional independence to people with paralysis. Though supported by decades of preclinical data, the safety of chronically implanted microelectrode array BCIs in humans is unknown. We report safety results from the prospective, open-label, nonrandomized BrainGate feasibility study (NCT00912041), the largest and longest-running clinical trial of an implanted BCI. METHODS: Adults aged 18-75 years with quadriparesis from spinal cord injury, brainstem stroke, or motor neuron disease were enrolled through 7 clinical sites in the United States. Participants underwent surgical implantation of 1 or 2 microelectrode arrays in the motor cortex of the dominant cerebral hemisphere. The primary safety outcome was device-related serious adverse events (SAEs) requiring device explantation or resulting in death or permanently increased disability during the 1-year postimplant evaluation period. The secondary outcomes included the type and frequency of other adverse events and the feasibility of the BrainGate system for controlling a computer or other assistive technologies. RESULTS: From 2004 to 2021, 14 adults enrolled in the BrainGate trial had devices surgically implanted. The average duration of device implantation was 872 days, yielding 12,203 days of safety experience. There were 68 device-related adverse events, including 6 device-related SAEs. The most common device-related adverse event was skin irritation around the percutaneous pedestal. There were no safety events that required device explantation, no unanticipated adverse device events, no intracranial infections, and no participant deaths or adverse events resulting in permanently increased disability related to the investigational device. DISCUSSION: The BrainGate Neural Interface system has a safety record comparable with other chronically implanted medical devices. Given rapid recent advances in this technology and continued performance gains, these data suggest a favorable risk/benefit ratio in appropriately selected individuals to support ongoing research and development. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT00912041. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the neurosurgically placed BrainGate Neural Interface system is associated with a low rate of SAEs defined as those requiring device explantation, resulting in death, or resulting in permanently increased disability during the 1-year postimplant period.

Closed-loop enhancement and neural decoding of cognitive control in humans.

Deficits in cognitive control-that is, in the ability to withhold a default pre-potent response in favour of a more adaptive choice-are common in depression, anxiety, addiction and other mental disorders. Here we report proof-of-concept evidence that, in participants undergoing intracranial epilepsy monitoring, closed-loop direct stimulation of the internal capsule or striatum, especially the dorsal sites, enhances the participants' cognitive control during a conflict task. We also show that closed-loop stimulation upon the detection of lapses in cognitive control produced larger behavioural changes than open-loop stimulation, and that task performance for single trials can be directly decoded from the activity of a small number of electrodes via neural features that are compatible with existing closed-loop brain implants. Closed-loop enhancement of cognitive control might remediate underlying cognitive deficits and aid the treatment of severe mental disorders.

Catalytic conversion of heavy naphtha to reformate over the phosphorus-ZSM-5 catalyst at a lower reforming temperature.

Naphtha reforming to aromatics, naphthenes, and iso-paraffins is an essential process to increase the octane number of gasoline through the utilization of middle naphtha (whole). A ZSM-5 zeolite catalyst with modified medium pores was developed to comprehend the existing limitation of catalytic reforming to the unutilized refinery feedstock of heavy naphtha. The study applied a lower reforming conversion temperature (350 °C) than a conventional reformer without noble metal addition in an effort to lower the carbon footprint of the process and catalyst cost. The modified zeolite catalyst was impregnated with phosphorus oxide and spray-dried, followed by a hydrothermal treatment with steam. The parent and modified catalysts were characterized by NH3-TPD, SEM, XRD, NMR, FTIR, and N2 physisorption. Steam treatment was conducted to reduce the original zeolite acidity, mainly in the form of Brønsted acid sites, which resulted in the formation of phosphorus-aluminum species in the framework. The modified catalyst consisting of 40% ZSM-5 and 60% binder delivered high conversion of dodecane, and the reforming reaction selectivity favored the formation of carbonium ions through ß-scission. Therefore, monomolecular cracking took place, resulting in the production of olefins and paraffin alongside iso-paraffins, aromatics, and naphthenes, which are associated with the bimolecular pathway. The reforming of heavy naphtha was different; the free radicals from ß-scission were affected by the surrounding molecules of feedstock, and the bimolecular reactions were more dominant through zeolite pores. The study demonstrated that the addition of 10% steam during the reaction of heavy naphtha suppressed coke formation. Furthermore, high conversion and steady selectivity were maintained during the reaction, which resulted in gasoline reformate with a high research octane number (RON).

Steam Catalytic Cracking of n-Dodecane to Light Olefins over Phosphorous- and Metal-Modified Nanozeolite Y.

Nanozeolite Y was synthesized without a template and modified with phosphorous (P) and metals. P was introduced via impregnation with different weight loadings (0.5, 1, and 2 wt %), while ion exchange was developed to introduce zirconium (Zr) and cobalt (Co). The physicochemical properties of the catalysts were characterized with X-ray diffraction (XRD), N2 adsorption-desorption, temperature-programmed desorption of ammonia (NH3-TPD), and 27Al and 31P solid-state nuclear magnetic resonance (NMR). The parent nanozeolite Y showed an identical XRD pattern to that of a previous study, and the modified nanozeolite Y showed a lower crystallinity. The introduction of P altered tetrahedral Al to an octahedral coordination, which affected the catalyst acidity. Then, the catalyst was evaluated to produce olefins from n-dodecane at 550, 575, and 600 °C. The conversion, gas yield, and olefin yield increased with increasing temperature. The maximum olefin yield (63%) was achieved with the introduction of 1 wt % P with the highest selectivity to ethylene. The Co-modified nanozeolite altered the zeolite structure and exhibited similar activity to the P-modified one. Meanwhile, Zr-modified nanozeolite Y caused excessive metal distribution, blocked the porous structure of the zeolite, and then reduced the catalytic activity.

Cortical Ripples during NREM Sleep and Waking in Humans.

Hippocampal ripples index the reconstruction of spatiotemporal neuronal firing patterns essential for the consolidation of memories in the cortex during non-rapid eye movement sleep (NREM). Recently, cortical ripples in humans have been shown to enfold the replay of neuron firing patterns during cued recall. Here, using intracranial recordings from 18 patients (12 female), we show that cortical ripples also occur during NREM in humans, with similar density, oscillation frequency (∼90 Hz), duration, and amplitude to waking. Ripples occurred in all cortical regions with similar characteristics, unrelated to putative hippocampal connectivity, and were less dense and robust in higher association areas. Putative pyramidal and interneuron spiking phase-locked to cortical ripples during NREM, with phase delays consistent with ripple generation through pyramidal-interneuron feedback. Cortical ripples were smaller in amplitude than hippocampal ripples but were similar in density, frequency, and duration. Cortical ripples during NREM typically occurred just before the upstate peak, often during spindles. Upstates and spindles have previously been associated with memory consolidation, and we found that cortical ripples grouped cofiring between units within the window of spike timing-dependent plasticity. Thus, human NREM cortical ripples are as follows: ubiquitous and stereotyped with a tightly focused oscillation frequency; similar to hippocampal ripples; associated with upstates and spindles; and associated with unit cofiring. These properties are consistent with cortical ripples possibly contributing to memory consolidation and other functions during NREM in humans.SIGNIFICANCE STATEMENT In rodents, hippocampal ripples organize replay during sleep to promote memory consolidation in the cortex, where ripples also occur. However, evidence for cortical ripples in human sleep is limited, and their anatomic distribution and physiological properties are unexplored. Here, using human intracranial recordings, we demonstrate that ripples occur throughout the cortex during waking and sleep with highly stereotyped characteristics. During sleep, cortical ripples tend to occur during spindles on the down-to-upstate transition, and thus participate in a sequence of sleep waves that is important for consolidation. Furthermore, cortical ripples organize single-unit spiking with timing optimal to facilitate plasticity. Therefore, cortical ripples in humans possess essential physiological properties to support memory and other cognitive functions.

Responsive Thalamic Neurostimulation: A Systematic Review of a Promising Approach for Refractory Epilepsy.

Introduction: Responsive neurostimulation is an evolving therapeutic option for patients with treatment-refractory epilepsy. Open-loop, continuous stimulation of the anterior thalamic nuclei is the only approved modality, yet chronic stimulation rarely induces complete seizure remission and is associated with neuropsychiatric adverse effects. Accounts of off-label responsive stimulation in thalamic nuclei describe significant improvements in patients who have failed multiple drug regimens, vagal nerve stimulation, and other invasive measures. This systematic review surveys the currently available data supporting the use of responsive thalamic neurostimulation in primary and secondary generalized, treatment-refractory epilepsy. Materials and Methods: A systematic review was performed using the following combination of keywords and controlled vocabulary: ("Seizures"[Mesh] AND "Thalamus"[Mesh] AND "Deep Brain Stimulation"[Mesh]) OR (responsive neurostim* AND (thalamus[MeSH])) OR [responsive neurostimulation AND thalamus AND (epilepsy OR seizures)]. In addition, a search of the publications listed under the PubMed "cited by" tab was performed for all publications that passed title/abstract screening in addition to manually searching their reference lists. Results: Ten publications were identified describing a total of 29 subjects with a broad range of epilepsy disorders treated with closed-loop thalamic neurostimulation. The median age of subjects was 31 years old (range 10-65 years). Of the 29 subjects, 15 were stimulated in the anterior, 11 in the centromedian, and 3 in the pulvinar nuclei. Excluding 5 subjects who were treated for 1 month or less, median time on stimulation was 19 months (range 2.4-54 months). Of these subjects, 17/24 experienced greater than or equal to 50%, 11/24 least 75%, and 9/24 at least 90% reduction in seizures. Although a minority of patients did not exhibit significant clinical improvement by follow-up, there was a general trend of increasing treatment efficacy with longer periods on closed-loop thalamic stimulation. Conclusion: The data supporting off-label closed-loop thalamic stimulation for refractory epilepsy is limited to 29 adult and pediatric patients, many of whom experienced significant improvement in seizure duration and frequency. This encouraging progress must be verified in larger studies.

Acidity modifications of nanozeolite-Y for enhanced selectivity to olefins from the steam catalytic cracking of dodecane.

Nanozeolite-Y was synthesized in the absence of a templating agent with several modification methods. The parent nanozeolite-Y was prepared with different sodium (Na) contents and crystallization conditions. Then, the parent nanozeolite-Y was modified by ion exchange, calcination, and steam treatment. The treatment caused insignificant changes to the ratio of alumina and silica but altered the zeolite acid sites. The Lewis and Brønsted acidity changed after the treatment depending on the modification approach, as indicated by the FTIR spectroscopy of pyridine. The ammonia temperature programmed desorption (NH3-TPD) confirmed that the acid sites consisted of weak and medium sites, which decreased after modifications. Moreover, the solid-state nuclear magnetic resonance (NMR) spectroscopy revealed that the position of Al shifted from tetrahedral to a combined octahedral and pentahedral framework. The catalytic evaluation for dodecane cracking at 550 °C shows the gas yield as the main product with naphtha as a side product. The gas yield consisted of 50% light olefins from ethylene to butene. However, the process yielded 9% of coke that led to faster catalyst deactivation because of nanozeolite-Y evolution and product transformation.

Widespread ripples synchronize human cortical activity during sleep, waking, and memory recall.

Declarative memory encoding, consolidation, and retrieval require the integration of elements encoded in widespread cortical locations. The mechanism whereby such "binding" of different components of mental events into unified representations occurs is unknown. The "binding-by-synchrony" theory proposes that distributed encoding areas are bound by synchronous oscillations enabling enhanced communication. However, evidence for such oscillations is sparse. Brief high-frequency oscillations ("ripples") occur in the hippocampus and cortex and help organize memory recall and consolidation. Here, using intracranial recordings in humans, we report that these ∼70-ms-duration, 90-Hz ripples often couple (within ±500 ms), co-occur (≥ 25-ms overlap), and, crucially, phase-lock (have consistent phase lags) between widely distributed focal cortical locations during both sleep and waking, even between hemispheres. Cortical ripple co-occurrence is facilitated through activation across multiple sites, and phase locking increases with more cortical sites corippling. Ripples in all cortical areas co-occur with hippocampal ripples but do not phase-lock with them, further suggesting that cortico-cortical synchrony is mediated by cortico-cortical connections. Ripple phase lags vary across sleep nights, consistent with participation in different networks. During waking, we show that hippocampo-cortical and cortico-cortical coripples increase preceding successful delayed memory recall, when binding between the cue and response is essential. Ripples increase and phase-modulate unit firing, and coripples increase high-frequency correlations between areas, suggesting synchronized unit spiking facilitating information exchange. co-occurrence, phase synchrony, and high-frequency correlation are maintained with little decrement over very long distances (25 cm). Hippocampo-cortico-cortical coripples appear to possess the essential properties necessary to support binding by synchrony during memory retrieval and perhaps generally in cognition.

Phasic stimulation in the nucleus accumbens enhances learning after traumatic brain injury.

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality worldwide. Despite improvements in survival, treatments that improve functional outcome remain lacking. There is, therefore, a pressing need to develop novel treatments to improve functional recovery. Here, we investigated task-matched deep-brain stimulation of the nucleus accumbens (NAc) to augment reinforcement learning in a rodent model of TBI. We demonstrate that task-matched deep brain stimulation (DBS) of the NAc can enhance learning following TBI. We further demonstrate that animals receiving DBS exhibited greater behavioral improvement and enhanced neural proliferation. Treated animals recovered to an uninjured behavioral baseline and showed retention of improved performance even after stimulation was stopped. These results provide encouraging early evidence for the potential of NAc DBS to improve functional outcomes following TBI and that its effects may be broad, with alterations in neurogenesis and synaptogenesis.