Intracranial Directed Connectivity Links Subregions of the Prefrontal Cortex to Major Depression.

Understanding the neural basis of major depressive disorder (MDD) is vital to guiding neuromodulatory treatments. The available evidence supports the hypothesis that MDD is fundamentally a disease of cortical disinhibition, where breakdowns of inhibitory neural systems lead to diminished emotion regulation and intrusive ruminations. Recent research also points towards network changes in the brain, especially within the prefrontal cortex (PFC), as primary sources of MDD etiology. However, due to limitations in spatiotemporal resolution and clinical opportunities for intracranial recordings, this hypothesis has not been directly tested. We recorded intracranial EEG from the dorsolateral (dlPFC), orbitofrontal (OFC), and anterior cingulate cortices (ACC) in neurosurgical patients with MDD. We measured daily fluctuations in self-reported depression severity alongside directed connectivity between these PFC subregions. We focused primarily on delta oscillations (1-3 Hz), which have been linked to GABAergic inhibitory control and intracortical communication. Depression symptoms worsened when connectivity within the left vs. right PFC became imbalanced. In the left hemisphere, all directed connectivity towards the ACC, from the dlPFC and OFC, was positively correlated with depression severity. In the right hemisphere, directed connectivity between the OFC and dlPFC increased with depression severity as well. This is the first evidence that delta oscillations flowing between prefrontal subregions transiently increase intensity when people are experiencing more negative mood. These findings support the overarching hypothesis that MDD worsens with prefrontal disinhibition.

Radiographic abnormalities and their clinical significance in patients with Parkinson disease who receive deep brain stimulation implants.

OBJECTIVE: Preoperative MR images obtained in patients with Parkinson disease (PD) undergoing deep brain stimulation (DBS) often reveal incidental radiographic abnormalities (RAs). These findings range from small changes to gross pathologies. The effect of these findings on patients' clinical outcomes is unknown. The authors characterized RAs in patients with PD who underwent DBS and assessed clinical outcomes. METHODS: Records of patients at the authors' institution with PD who underwent MRI for DBS electrode implantation from 2010 through 2022 were reviewed. RAs were identified from the official preoperative MRI reports. RAs were grouped into four general categories (ischemic changes, atrophy or degenerative changes [ADCs], structural abnormalities, and tumors) and correlated with clinical outcomes (including subjective clinical response, levodopa equivalent dose [LED], and Unified Parkinson's Disease Rating Scale Part III [UPDRS] score) at the 1-year and last available follow-ups. RESULTS: In this review, 160 patients were identified for initial analysis, with 135 presenting with ≥ 1 RAs. Of these 135 patients, 69.4% (111/160) had ischemic vascular changes, 39.4% (63/160) had ADCs, 16.9% (27/160) had structural changes, and 1.9% (3/160) had tumors. No differences in preoperative LED or UPDRS score were observed between these groups. After DBS, no differences in outcomes were observed between patients with RAs and those without RAs for both the 1-year and last follow-up time points, including mortality rates and times. Structural lesions were associated with lower mortality rates (OR 0.1, p = 0.04). ADCs were associated with a worse subjective clinical response at the 1-year (OR 0.50, p = 0.04) and last (OR 0.49, p = 0.03) follow-ups, but subjectively worse responses were not correlated with worse objective outcome measures. CONCLUSIONS: Most RAs have no significant effect on clinical outcomes in PD patients undergoing DBS. Generalized ADCs may be associated with poorer subjective responses and may warrant further discussion with the patient if diagnosed on preoperative MRI.

Beta activity in human anterior cingulate cortex mediates reward biases.

The rewards that we get from our choices and actions can have a major influence on our future behavior. Understanding how reward biasing of behavior is implemented in the brain is important for many reasons, including the fact that diminution in reward biasing is a hallmark of clinical depression. We hypothesized that reward biasing is mediated by the anterior cingulate cortex (ACC), a cortical hub region associated with the integration of reward and executive control and with the etiology of depression. To test this hypothesis, we recorded neural activity during a biased judgment task in patients undergoing intracranial monitoring for either epilepsy or major depressive disorder. We found that beta (12-30 Hz) oscillations in the ACC predicted both associated reward and the size of the choice bias, and also tracked reward receipt, thereby predicting bias on future trials. We found reduced magnitude of bias in depressed patients, in whom the beta-specific effects were correspondingly reduced. Our findings suggest that ACC beta oscillations may orchestrate the learning of reward information to guide adaptive choice, and, more broadly, suggest a potential biomarker for anhedonia and point to future development of interventions to enhance reward impact for therapeutic benefit.

Disruption of neural periodicity predicts clinical response after deep brain stimulation for obsessive-compulsive disorder.

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high degree of predictability. In patients with persistent symptoms (non-responders), predictability of the neural data remained consistently high. On the other hand, in patients who improved symptomatically (responders), predictability of the neural data was significantly diminished. This neural feature accurately classified clinical status even in patients with limited duration recordings, indicating generalizability that could facilitate therapeutic decision-making.

Insula uses overlapping codes for emotion in self and others.

In daily life, we must recognize others' emotions so we can respond appropriately. This ability may rely, at least in part, on neural responses similar to those associated with our own emotions. We hypothesized that the insula, a cortical region near the junction of the temporal, parietal, and frontal lobes, may play a key role in this process. We recorded local field potential (LFP) activity in human neurosurgical patients performing two tasks, one focused on identifying their own emotional response and one on identifying facial emotional responses in others. We found matching patterns of gamma- and high-gamma band activity for the two tasks in the insula. Three other regions (MTL, ACC, and OFC) clearly encoded both self- and other-emotions, but used orthogonal activity patterns to do so. These results support the hypothesis that the insula plays a particularly important role in mediating between experienced vs. observed emotions.

Default mode network electrophysiological dynamics and causal role in creative thinking.

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally-directed cognition. The present study employs stereo-electroencephalography in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thinking: spontaneous and divergent thought. We probe these two DMN-associated higher cognitive functions through mind wandering and alternate uses tasks, respectively. Our results reveal DMN recruitment during both tasks, as well as a task-specific dissociation in spatiotemporal response dynamics. When compared to the fronto-parietal network, DMN activity was characterized by a stronger increase in gamma band power (30-70 Hz) coupled with lower theta band power (4-8 Hz). The difference in activity between the two networks was especially strong during the mind wandering task. Within the DMN, we found that the tasks showed different dynamics, with the alternate uses task engaging the DMN more during the initial stage of the task, and mind wandering in the later stage. Gamma power changes were mainly driven by lateral DMN sites, while theta power displayed task-specific effects. During alternate uses task, theta changes did not show spatial differences within the DMN, while mind wandering was associated to an early lateral and late dorsomedial DMN engagement. Furthermore, causal manipulations of DMN regions using direct cortical stimulation preferentially decreased the originality of responses in the alternative uses task, without affecting fluency or mind wandering. Our results suggest that DMN activity is flexibly modulated as a function of specific cognitive processes and supports its causal role in divergent thinking. These findings shed light on the neural constructs supporting different forms of cognition and provide causal evidence for the role of DMN in the generation of original connections among concepts.

Demographics of focused ultrasound thalamotomy for essential tremor and trends in deep brain stimulation surgery after its introduction in the USA.

Background: Essential tremor (ET) is a movement disorder that affects 4%-5% of adults >65 years. For patients with medically refractory ET, neurosurgical interventions such as deep brain stimulation (DBS) and unilateral MR-guided focused ultrasound thalamotomy (MRgFUS) are available. In this retrospective cohort study, we examined the demographics of patients with ET who have received MRgFUS and evaluated trends in DBS usage in the USA after the introduction of MRgFUS in 2016. Methods: We used multiple databases to examine the demographics of patients who received DBS and MRgFUS, and trends in DBS. To assess the demographics, we queried the TriNetX database from 2003 to 2022 to identify patients diagnosed with ET and stratify them by DBS or MRgFUS treatment by using Current Procedural Terminology codes. Patient demographics were reported as frequencies and percentages. To examine the trends in DBS for ET, the yearly frequency of DBS procedures done for ET between 2012 and 2019 was extracted from the National Inpatient Sample (NIS) database, and breakpoint analysis was performed. Additionally, the yearly frequency of MRgFUS procedures for ET was obtained from Insightec Exlabate. Results: Most of the patients (88.69%) in the cohort extracted from TriNetX database self-identified as white, followed by black or African American (2.40%) and Asian (0.52%). A higher percentage of black patients received MRgFUS treatment than DBS (4.10% vs 1.88%). According to the NIS database, from 2012 to 2020, 13 525 patients received DBS for ET. Conclusion: This study provides an overview of the characteristics of patients who undergo DBS or MRgFUS. We found notable differences in sex and race among patients who underwent each treatment type. Additionally, until at least the beginning of 2020, the number of DBS procedures for ET was not negatively affected after the introduction of MRgFUS.

Delays in the diagnosis and surgical treatment of drug-resistant epilepsy: A cohort study.

OBJECTIVE: Delay in referral for epilepsy surgery of patients with drug-resistant epilepsy (DRE) is associated with decreased quality of life, worse surgical outcomes, and increased risk of sudden unexplained death in epilepsy (SUDEP). Understanding the potential causes of delays in referral and treatment is crucial for optimizing the referral and treatment process. We evaluated the treatment intervals, demographics, and clinical characteristics of patients referred for surgical evaluation at our level 4 epilepsy center in the U.S. Intermountain West. METHODS: We retrospectively reviewed the records of patients who underwent surgery for DRE between 2012 and 2022. Data collected included patient demographics, DRE diagnosis date, clinical characteristics, insurance status, distance from epilepsy center, date of surgical evaluation, surgical procedure, and intervals between different stages of evaluation. RESULTS: Within our cohort of 185 patients with epilepsy (99 female, 53.5%), the mean ± standard deviation (SD) age at surgery was 38.4 ± 11.9 years. In this cohort, 95.7% of patients had received definitive epilepsy surgery (most frequently neuromodulation procedures) and 4.3% had participated in phase 2 intracranial monitoring but had not yet received definitive surgery. The median (1st-3rd quartile) intervals observed were 10.1 (3.8-21.5) years from epilepsy diagnosis to DRE diagnosis, 16.7 (6.5-28.4) years from epilepsy diagnosis to surgery, and 1.4 (0.6-4.0) years from DRE diagnosis to surgery. We observed significantly shorter median times from epilepsy diagnosis to DRE diagnosis (p < .01) and epilepsy diagnosis to surgery (p < .05) in patients who traveled further for treatment. Patients with public health insurance had a significantly longer time from DRE diagnosis to surgery (p < .001). SIGNIFICANCE: Both shorter distance traveled to our epilepsy center and public health insurance were predictive of delays in diagnosis and treatment intervals. Timely referral of patients with DRE to specialized epilepsy centers for surgery evaluation is crucial, and identifying key factors that may delay referral is paramount to optimizing surgical outcomes.

Disparities in the treatment of movement disorders using deep brain stimulation.

OBJECTIVE: Deep brain stimulation (DBS) is a well-established treatment for Parkinson's disease (PD) and essential tremor (ET). Although the prevalence of PD and ET can vary by sex and race, little is known about the accessibility of neurosurgical treatments for these conditions. In this nationwide study, the authors aimed to characterize trends in the use of DBS for the treatment of PD and ET and to identify disparities in the neurosurgical treatment of these diseases based on ethnic, racial, sex, insurance, income, hospital, and geographic factors. METHODS: Using the dates January 1, 2012, to December 31, 2019, the authors queried the National Inpatient Sample database for all discharges with an ICD-9 or ICD-10 diagnosis of PD or ET. Among these discharges, the DBS rates were reported for each subgroup of race, ethnicity, and sex. To develop national estimates, all analyses were weighted. RESULTS: Among 2,517,639 discharges with PD, 29,820 (1.2%) received DBS, and among 652,935 discharges with ET, 11,885 (1.8%) received DBS. Amid the PD cases, Black patients (n = 405 [0.2%], OR 0.16, 95% CI 0.12-0.20) were less likely than White patients (n = 23,975 [1.2%]) to receive DBS treatment, as were Hispanic patients (n = 1965 [1.1%], OR 0.76, 95% CI 0.65-0.88), whereas Asian/Pacific Islander patients (n = 855 [1.5%]) did not statistically differ from White patients. Amid the ET cases, Black (n = 230 [0.8%], OR 0.39, 95% CI 0.27-0.56), Hispanic (n = 215 [1.0%], OR 0.39, 95% CI 0.28-0.55), and Asian/Pacific Islander (n = 55 [1.0%], OR 0.51, 95% CI 0.28-0.93) patients were less likely than White patients (n = 10,440 [1.9%]) to receive DBS. Females were less likely than males to receive DBS for PD (OR 0.69, p < 0.0001) or ET (OR 0.70, p < 0.0001). CONCLUSIONS: The authors describe significant racial and sex-based differences in the utilization of DBS for the treatment of PD and ET. Further research is required to ascertain the causes of these disparities, as well as any differences in access to specialty neurosurgical care and referral for neuromodulation approaches.

Optimization of Radiofrequency Needle Placement in Percutaneous Cordotomy Using Electromyography in the Deeply Sedated Patient.

BACKGROUND AND OBJECTIVES: Cordotomy, the selective disconnection of the nociceptive fibers in the spinothalamic tract, is used to provide pain palliation to oncological patients suffering from intractable cancer-related pain. Cordotomies are commonly performed using a cervical (C1-2) percutaneous approach under imaging guidance and require patients' cooperation to functionally localize the spinothalamic tract. This can be challenging in patients suffering from extreme pain. It has recently been demonstrated that intraoperative neurophysiology monitoring by electromyography may aid in safe lesion positioning. The aim of this study was to evaluate the role of compound muscle action potential (CMAP) in deeply sedated patients undergoing percutaneous cervical cordotomy (PCC). METHODS: A retrospective analysis was conducted of all patients who underwent percutaneous cordotomy while deeply sedated between January 2019 and November 2022 in 2 academic centers. The operative report, neuromonitoring logs, and clinical medical records were evaluated. RESULTS: Eleven patients underwent PCC under deep sedation. In all patients, the final motor assessment prior to ablation was done using the electrophysiological criterion alone. The median threshold for evoking CMAP activity at the lesion site was 0.9 V ranging between 0.5 and 1.5 V (average 1 V ± 0.34 V SD). An immediate, substantial decrease in pain was observed in 9 patients. The median pain scores (Numeric Rating Scale) decreased from 10 preoperatively (range 8-10) to a median 0 (range 0-10) immediately after surgery. None of our patients developed motor deficits. CONCLUSION: CMAP-guided PCC may be feasible in deeply sedated patients without added risk to postoperative motor function. This technique should be considered in a group of patients who are not able to undergo awake PCC.

Disparities in Access to Deep Brain Stimulation and Responsive Neurostimulation Approaches to Drug-Resistant Epilepsy.

BACKGROUND: Epilepsy affects 1% to 2% of the global population, and those who are resistant to medical treatment may be candidates for neuromodulation. In select populations, brain stimulation approaches including deep brain stimulation (DBS) and responsive neurostimulation (RNS) are used. Although studies have shown that patients from Black, Hispanic, lower income, and rural communities have less access to epilepsy care and have lower rates of epilepsy surgery, disparities in the use of brain stimulation for epilepsy treatment are currently not known. MATERIALS AND METHODS: We queried the US National Inpatient Sample data base from January 1, 2014 to December 31, 2019 for all patients discharged with an International Classification of Diseases (ICD) Ninth Revision or ICD Tenth Revision diagnosis of drug-resistant epilepsy. Among these patients discharged, the rates of brain stimulation treatment, including DBS and RNS, were reported in each subgroup of race, ethnicity, and insurance. To generate national estimates, all analyses were weighted. RESULTS: A total of 237,895 patients discharged with drug-resistant epilepsy were identified, of whom 4,925 (2.1%) received brain stimulation treatment for drug-resistant epilepsy. Black patients (n = 420, 0.9%, odds ratio [OR] = 0.51, 95% CI [0.40, 0.64]) were less likely to receive brain stimulation treatment than were White patients (n = 3300, 2.4%). There was no significant difference between Asian (n = 105, 2.3%, OR = 0.80, 95% CI [0.53, 1.33]) and Hispanic (n = 655, 2.6%, OR = 0.95, 95% CI [0.77, 1.17]) patients and White patients. No significant difference was observed between female (n = 2515, 2.1%, OR = 1.02, 95% CI [0.89, 1.17]) and male (n = 2410, 2.0%) patients either. Patients with Medicare (n = 1150, 1.2%, OR = 0.69, 95% CI [0.57, 0.84]) or Medicaid (n = 1150, 1.8%, OR = 0.52, 95% CI [0.44, 0.62]) were less likely to receive brain stimulation treatment than were those with private insurance as the primary payer (n = 2370, 3.9%). CONCLUSIONS: We discovered significant disparities in the use of brain stimulation treatments for drug-resistant epilepsy based on race and insurance status. More research will be required to determine the cause of these disparities.

Stereo-EEG-guided network modulation for psychiatric disorders: Surgical considerations.

BACKGROUND: Deep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders. OBJECTIVE: /Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challenging disorder, we adopted an approach of inpatient intracranial monitoring borrowed from the epilepsy surgery field. METHODS: We implanted 3 patients with 4 DBS leads (bilateral pair in both the ventral capsule/ventral striatum and subcallosal cingulate) and 10 stereo-electroencephalography (sEEG) electrodes targeting depression-relevant network regions. For surgical planning, we used an interactive, holographic visualization platform to appreciate the 3D anatomy and connectivity. In the initial surgery, we placed the DBS leads and sEEG electrodes using robotic stereotaxy. Subjects were then admitted to an inpatient monitoring unit for depression-specific neurophysiological assessments. Following these investigations, subjects returned to the OR to remove the sEEG electrodes and internalize the DBS leads to implanted pulse generators. RESULTS: Intraoperative testing revealed positive valence responses in all 3 subjects that helped verify targeting. Given the importance of the network-based hypotheses we were testing, we required accurate adherence to the surgical plan (to engage DBS and sEEG targets) and stability of DBS lead rotational position (to ensure that stimulation field estimates of the directional leads used during inpatient monitoring were relevant chronically), both of which we confirmed (mean radial error 1.2±0.9 mm; mean rotation 3.6±2.6°). CONCLUSION: This novel hybrid sEEG-DBS approach allows detailed study of the neurophysiological substrates of complex neuropsychiatric disorders.

Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

Intracranial stimulation and EEG feature analysis reveal affective salience network specialization.

Emotion is represented in limbic and prefrontal brain areas, herein termed the affective salience network (ASN). Within the ASN, there are substantial unknowns about how valence and emotional intensity are processed-specifically, which nodes are associated with affective bias (a phenomenon in which participants interpret emotions in a manner consistent with their own mood). A recently developed feature detection approach ('specparam') was used to select dominant spectral features from human intracranial electrophysiological data, revealing affective specialization within specific nodes of the ASN. Spectral analysis of dominant features at the channel level suggests that dorsal anterior cingulate (dACC), anterior insula and ventral-medial prefrontal cortex (vmPFC) are sensitive to valence and intensity, while the amygdala is primarily sensitive to intensity. Akaike information criterion model comparisons corroborated the spectral analysis findings, suggesting all four nodes are more sensitive to intensity compared to valence. The data also revealed that activity in dACC and vmPFC were predictive of the extent of affective bias in the ratings of facial expressions-a proxy measure of instantaneous mood. To examine causality of the dACC in affective experience, 130 Hz continuous stimulation was applied to dACC while patients viewed and rated emotional faces. Faces were rated significantly happier during stimulation, even after accounting for differences in baseline ratings. Together the data suggest a causal role for dACC during the processing of external affective stimuli.

Tractography-Based Modeling Explains Treatment Outcomes in Patients Undergoing Deep Brain Stimulation for Obsessive-Compulsive Disorder.

BACKGROUND: Deep brain stimulation (DBS) is an established and expanding therapy for treatment-refractory obsessive-compulsive disorder. Previous work has suggested that a white matter circuit providing hyperdirect input from the dorsal cingulate and ventrolateral prefrontal regions to the subthalamic nucleus could be an effective neuromodulatory target. METHODS: We tested this concept by attempting to retrospectively explain through predictive modeling the ranks of clinical improvement as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) in 10 patients with obsessive-compulsive disorder who underwent DBS to the ventral anterior limb of internal capsule with subsequent programming uninformed by the putative target tract. RESULTS: Rank predictions were carried out using the tract model by a team that was completely uninvolved in DBS planning and programming. Predicted Y-BOCS improvement ranks significantly correlated with actual Y-BOCS improvement ranks at the 6-month follow-up (r = 0.75, p = .013). Predicted score improvements correlated with actual Y-BOCS score improvements (r = 0.72, p = .018). CONCLUSIONS: Here, we provide data in a first-of-its-kind report suggesting that normative tractography-based modeling can blindly predict treatment response in DBS for obsessive-compulsive disorder.

Neurosurgical Approaches for Treatment-Resistant Obsessive-Compulsive Disorder.

Treatment-resistant obsessive-compulsive disorder (trOCD) is a severely disabling, life-threatening psychiatric disorder affecting ∼0.5% of the US population. Following the failure of multiple medical and psychotherapeutic treatment lines, patients with trOCD, like others with functional disorders, may benefit from invasive neuromodulation. Cumulative evidence suggests that disrupting abnormal hyperdirect cortico-striato-thalamo-cortical (CSTC) pathway activity offers sustainable, robust symptomatic relief in most patients. Multiple surgical approaches allow for modulation of the CSTC pathway, including stereotactic lesions and electrical stimulation. This review aims to describe the modern neurosurgical approaches for trOCD, recent advances in our understanding of pathophysiology, and future therapeutic directions.

Decoding Depression Severity From Intracranial Neural Activity.

BACKGROUND: Disorders of mood and cognition are prevalent, disabling, and notoriously difficult to treat. Fueling this challenge in treatment is a significant gap in our understanding of their neurophysiological basis. METHODS: We recorded high-density neural activity from intracranial electrodes implanted in depression-relevant prefrontal cortical regions in 3 human subjects with severe depression. Neural recordings were labeled with depression severity scores across a wide dynamic range using an adaptive assessment that allowed sampling with a temporal frequency greater than that possible with typical rating scales. We modeled these data using regularized regression techniques with region selection to decode depression severity from the prefrontal recordings. RESULTS: Across prefrontal regions, we found that reduced depression severity is associated with decreased low-frequency neural activity and increased high-frequency activity. When constraining our model to decode using a single region, spectral changes in the anterior cingulate cortex best predicted depression severity in all 3 subjects. Relaxing this constraint revealed unique, individual-specific sets of spatiospectral features predictive of symptom severity, reflecting the heterogeneous nature of depression. CONCLUSIONS: The ability to decode depression severity from neural activity increases our fundamental understanding of how depression manifests in the human brain and provides a target neural signature for personalized neuromodulation therapies.

Association of clinical outcomes and connectivity in awake versus asleep deep brain stimulation for Parkinson disease.

OBJECTIVE: Deep brain stimulation (DBS) for Parkinson disease (PD) is traditionally performed with awake intraoperative testing and/or microelectrode recording. Recently, however, the procedure has been increasingly performed under general anesthesia with image-based verification. The authors sought to compare structural and functional networks engaged by awake and asleep PD-DBS of the subthalamic nucleus (STN) and correlate them with clinical outcomes. METHODS: Levodopa equivalent daily dose (LEDD), pre- and postoperative motor scores on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III), and total electrical energy delivered (TEED) at 6 months were retroactively assessed in patients with PD who received implants of bilateral DBS leads. In subset analysis, implanted electrodes were reconstructed using the Lead-DBS toolbox. Volumes of tissue activated (VTAs) were used as seed points in group volumetric and connectivity analysis. RESULTS: The clinical courses of 122 patients (52 asleep, 70 awake) were reviewed. Operating room and procedure times were significantly shorter in asleep cases. LEDD reduction, MDS-UPDRS III score improvement, and TEED at the 6-month follow-up did not differ between groups. In subset analysis (n = 40), proximity of active contact, VTA overlap, and desired network fiber counts with motor STN correlated with lower DBS energy requirement and improved motor scores. Discriminative structural fiber tracts involving supplementary motor area, thalamus, and brainstem were associated with optimal clinical improvement. Areas of highest structural and functional connectivity with VTAs did not significantly differ between the two groups. CONCLUSIONS: Compared to awake STN DBS, asleep procedures can achieve similarly optimal targeting-based on clinical outcomes, electrode placement, and connectivity estimates-in more efficient procedures and shorter operating room times.