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Amygdala activation by emotional arousal during memory formation can prioritize events for long-term memory. Building upon our prior demonstration that brief electrical stimulation to the human amygdala reliably improved long-term recognition memory for images of neutral objects without eliciting an emotional response, our study aims to explore and describe individual differences and stimulation-related factors in amygdala-mediated memory modulation. Thirty-one patients undergoing intracranial monitoring for intractable epilepsy were shown neutral object images paired with direct amygdala stimulation during encoding with recognition memory tested immediately and one day later. Adding to our prior sample, we found an overall memory enhancement effect without subjective emotional arousal at the one-day delay, but not at the immediate delay, for previously stimulated objects compared to not stimulated objects. Importantly, we observed a larger variation in performance across this larger sample than our initial sample, including some participants who showed a memory impairment for stimulated objects. Of the explored individual differences, the factor that most accounted for variability in memory modulation was each participant's pre-operative memory performance. Worse memory performance on standardized neuropsychological tests was associated with a stronger susceptibility to memory modulation in a positive or negative direction. Sex differences and the frequency of interictal epileptiform discharges (IEDs) during testing also accounted for some variance in amygdala-mediated memory modulation. Given the potential and challenges of this memory modulation approach, we discuss additional individual and stimulation factors that we hope will differentiate between memory enhancement and impairment to further optimize the potential of amygdala-mediated memory enhancement for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Stereotactic laser amygdalohippocampotomy (SLAH) is a minimally invasive procedure for mesial temporal lobe epilepsy that preserves more tissue than open procedures. As a result, although patients have better functional outcomes, more patients do not achieve seizure freedom. The rate at which this occurs is evolving with improved surgical practices. However, the risks and benefits of further surgical management for these patients remains a question with limited data to guide decision‐making.We retrospectively reviewed a continuous series (2011–2019) of SLAH operations at our institution to determine trends in surgical management, identifying cases where further surgery was performed. Pre‐operative and follow‐up seizure, cognitive, and functional data, and surgical complications were collated.Of 108 patients undergoing primary SLAH, 21 (19%) underwent further surgery (23 procedures). Stereo‐electroencephalography (SEEG) informed seven procedures (30%). There was a trend for quicker SLAH failure in the earlier patients. Similarly, surgical chronology was associated with progression to repeat surgery (p = .007). At 1‐year follow‐up, 6 of 13 patients (46%) achieved seizure freedom after repeat SLAH and 5 of 8 patients (63%) achieved seizure freedom after anterior temporal lobectomy (ATL), one of whom had failed two SLAHs. Two of three patients undergoing an ablation outside the mesial temporal lobe achieved seizure freedom at 1 year. Neuropsychological sequelae were more prevalent with ATL than SLAH, including decline in visual naming (p = .01) and functional status (p = .007).Repeat SLAH and ATL post‐SLAH are both practicable and can be effective. Surgical experience, risk to cognition, and marginal benefit relative to existing improvement are principal considerations for further surgery. [ABSTRACT FROM AUTHOR]

Many groups have reported lymphatic and glymphatic structures in animal and human brains, but tracer injection into the human brain to demonstrate real-time lymphatic drainage and mapping has not been described. We enrolled patients undergoing standard-of-care resection or stereotactic biopsy for suspected intracranial tumors. Patients received peritumoral injections of 99mTc-tilmanocept followed by planar or tomographic imaging. Fourteen patients with suspected brain tumors were enrolled. One was excluded from analysis because of tracer leakage during injection. There was no drainage of 99mTc-tilmanocept to regional lymph nodes in any of the patients. On average, after correcting for radioactive decay, 70.7% (95% CI: 59.9%, 81.6%) of the tracer in the injection site and 78.1% (95% CI: 71.1%, 85.1%) in the whole-head on the day of surgery remained the morning after, with variable radioactivity in the subarachnoid space. The retained fraction was much greater than expected based on the clearance rate from non-brain injection sites. In this pilot study, the lymphatic tracer 99mTc-tilmanocept was injected into the brain parenchyma, and there was no drainage outside the brain to the cervical lymph nodes. Our work demonstrates an inefficiency of drainage from peritumoral brain parenchyma and highlights a therapeutic opportunity to improve immunosurveillance of the brain. [ABSTRACT FROM AUTHOR]

Demonstrates that orexin-containing neurons of the hypothalamus directly monitor circulating indicators of energy balance and mediate adaptive augmentation of arousal in response to fasting. Electrophysiological activity of isolated enhanced green fluorescent protein-tagged orexin neurons inhibited by glucose, leptin and stimulated by ghrelin; Correlation of orexin expression with changes in blood glucose, leptin and food intake in normal and obese mice.

• This study compared visual confrontation naming and seizure control outcomes of three commonly used epilepsy surgery approaches: subtemporal approach selective amygdalohippocampectomy (subSAH), selective laser amygdalohippocampotomy (SLAH), and traditional anterior temporal lobectomy (ATL). • Group-level analyses revealed significant differences in naming outcome across the three groups: ATLs = worst naming outcome, subSAH = intermediate naming outcome, SLAH = best naming outcome. • Individual-level analyses revealed that no patient who underwent selective laser amygdalohippocampotomy (SLAH) showed significant naming decline after surgery and 36% showed improvement. • In contrast, 36% of subSAH and 82% of ATL patients showed significant postsurgical naming decline. • There were no significant differences across the three groups regarding postoperative seizure control. The purpose of this study was to systematically examine three different surgical approaches in treating left medial temporal lobe epilepsy (mTLE) (viz., subtemporal selective amygdalohippocampectomy [subSAH], stereotactic laser amygdalohippocampotomy [SLAH], and anterior temporal lobectomy [ATL]), to determine which procedures are most favorable in terms of visual confrontation naming and seizure relief outcome. This was a retrospective study of 33 adults with intractable mTLE who underwent left temporal lobe surgery at three different epilepsy surgery centers who also underwent pre-, and at least 6-month post-surgical neuropsychological testing. Measures included the Boston Naming Test (BNT) and the Engel Epilepsy Surgery Outcome Scale. Fisher's exact tests revealed a statistically significant decline in naming in ATLs compared to SLAHs, but no other significant group differences. 82% of ATL and 36% of subSAH patients showed a significant naming decline whereas no SLAH patient (0%) had a significant naming decline. Significant postoperative naming improvement was seen in 36% of SLAH patients in contrast to 9% improvement in subSAH patients and 0% improvement in ATLs. Finally, there were no statistically significant differences between surgical approaches with regard to seizure freedom outcome, although there was a trend towards better seizure relief outcome among the ATL patients. Results support a possible benefit of SLAH in preserving visual confrontation naming after left TLE surgery. While result interpretation is limited by the small sample size, findings suggest outcome is likely to differ by surgical approach, and that further research on cognitive and seizure freedom outcomes is needed to inform patients and providers of potential risks and benefits with each. [ABSTRACT FROM AUTHOR]

Background: Awake neurosurgery requires patients to converse and respond to visual or verbal prompts to identify and protect brain tissue supporting essential functions such as language, primary sensory modalities, and motor function. These procedures can be poorly tolerated because of patient anxiety, yet acute anxiolytic medications typically cause sedation and impair cortical function.Methods: In this study, direct electrical stimulation of the left dorsal anterior cingulum bundle was discovered to reliably evoke positive affect and anxiolysis without sedation in a patient with epilepsy undergoing research testing during standard inpatient intracranial electrode monitoring. These effects were quantified using subjective and objective behavioral measures, and stimulation was found to evoke robust changes in local and distant neural activity.Results: The index patient ultimately required an awake craniotomy procedure to confirm safe resection margins in the treatment of her epilepsy. During the procedure, cingulum bundle stimulation enhanced positive affect and reduced the patient's anxiety to the point that intravenous anesthetic/anxiolytic medications were discontinued and cognitive testing was completed. Behavioral responses were subsequently replicated in 2 patients with anatomically similar electrode placements localized to an approximately 1-cm span along the anterior dorsal cingulum bundle above genu of the corpus callosum.Conclusions: The current study demonstrates a robust anxiolytic response to cingulum bundle stimulation in 3 patients with epilepsy.Trial Registration: The current study was not affiliated with any formal clinical trial.Funding: This project was supported by the American Foundation for Suicide Prevention and the NIH. [ABSTRACT FROM AUTHOR]

A monosynaptic projection from the cortex to the subthalamic nucleus is thought to have an important role in basal ganglia function and in the mechanism of therapeutic subthalamic deep-brain stimulation, but in humans the evidence for its existence is limited. We sought physiological confirmation of the cortico-subthalamic hyperdirect pathway using invasive recording techniques in patients with Parkinson's disease (9 men, 1 woman). We measured sensorimotor cortical evoked potentials using a temporary subdural strip electrode in response to low-frequency deep-brain stimulation in patients undergoing awake subthalamic or pallidal lead implantations. Evoked potentials were grouped into very short latency (<2 ms), short latency (2-10 ms), and long latency (10-100 ms) from the onset of the stimulus pulse. Subthalamic and pallidal stimulation resulted in very short-latency evoked potentials at 1.5 ms in the primary motor cortex accompanied by EMG-evoked potentials consistent with corticospinal tract activation. Subthalamic, but not pallidal stimulation, resulted in three short-latency evoked potentials at 2.8,5.8, and 7.7 ms in a widespread cortical distribution, consistent with antidromic activation of the hyperdirect pathway. Long-latency potentials were evoked by both targets, with subthalamic responses lagging pallidal responses by 10-20 ms, consistent with orthodromic activation of the thalamocortical pathway. The amplitude of the first short-latency evoked potential was predictive of the chronic therapeutic stimulation contact. [ABSTRACT FROM AUTHOR]

• The burden of psychiatric symptoms (i.e., depression, anxiety) was significantly reduced following left or right stereotactic laser amygdalohippocampotomy in patients with temporal lobe epilepsy. • Findings appear comparable to published literature on patients undergoing anterior temporal lobectomy, including rates of symptom remission and de novo symptom occurrence. • Findings suggest a multifactorial contribution to mental health outcome (e.g., non-surgical life changes, surgical side effects, disease-related variables), and suggest that large datasets are required to truly understand contributory factors. Stereotactic laser amygdalohippocampotomy (SLAH) is a minimally invasive surgical treatment for drug-resistant temporal lobe epilepsy (TLE) that has comparable rates of seizure freedom to traditional open resective TLE surgery. The objective of this study was to determine psychiatric outcome (i.e., depression and anxiety changes, psychosis) after SLAH, to explore possible contributory factors to these changes, and to determine the prevalence of de novo psychopathology. We explored mood and anxiety in 37 adult patients with TLE undergoing SLAH using the Beck psychiatric symptoms scales (i.e., Beck Depression Inventory-II [BDI-II] and Beck Anxiety Inventory [BAI]) preoperatively and 6 months following surgery. Multivariable regression analysis was conducted to identify predictors of worse depression or anxiety symptoms following SLAH. The prevalence of de novo psychopathology following SLAH was also determined. We found a significant decrease in BDI-II (mean decline from 16.3 to 10.9, p = 0.004) and BAI (mean decline from 13.3 to 9.0, p = 0.045) scores following SLAH at the group level. While the rate of resolution of depression (from 62% to 49%) did not achieve statistical significance (p = 0.13, McNemar's), the rate of resolution of anxiety (from 57% to 35%) was statistically significant (p = 0.03, McNemar's). The de novo rate of psychopathology (i.e., new onset depression or anxiety) following SLAH was 1 of 7 (14%). Using a metric of meaningful change rather than complete symptom resolution, 16 of 37 (43%) patients experienced improvement in depression and 6 of 37 (16%) experienced worsening. For anxiety, 14 of 37 (38%) experienced meaningful improvement and 8 of 37 (22%) experienced worsening. Baseline performance on the Beck Scales was the only factor contributing to outcome status. In one of the first studies to evaluate psychiatric outcomes after SLAH, we found promising overall trends toward stability or significant improvement in symptom burden at the group level for both depression and anxiety. There was also a significant improvement in clinical anxiety, though the decrease in clinical depression was not significant, likely owing to the limitations of sample size. SLAH may improve overall psychiatric symptoms, similarly to traditional resective TLE surgery, but de novo psychopathology and postoperative psychiatric morbidity remain significant issues, and larger samples are necessary to determine causal contributory factors. [ABSTRACT FROM AUTHOR]