INTRODUCTION:Alzheimer's disease (AD) is biologically defined by amyloid beta and tau pathology. Available biomarkers enable early diagnosis but differ in targets, accessibility, and utility. This review synthesizes evidence for plasma biomarkers, magnetic resonance imaging (MRI), and positron emission tomography (PET) to develop a pragmatic, stage-aware framework for early diagnosis and staging. METHODS:We conducted a narrative review of recent literature and professional guidance (2024-2026) covering plasma biomarkers; structural/functional MRI; and amyloid, tau, and fluorodeoxyglucose (FDG) PET. Evidence was organized by biological target, diagnostic role, disease stage, and intended-use population. RESULTS:For symptomatic individuals, high-performance plasma biomarkers (especially phosphorylated tau at threonine 217 [p-tau217]) support scalable triage and biological enrichment. MRI provides anatomical, differential-diagnostic, and treatment-safety information. Amyloid PET offers biological confirmation; tau PET adds regional staging and prognosis; FDG PET characterizes synaptic dysfunction and distinguishes dementia patterns. Emerging endogenously cleaved microtubule-binding region tau containing residue 243 (eMTBR-tau243) and brain-derived p-tau217 remain investigational. In cognitively unimpaired at-risk individuals, routine screening is not implied; use is for research or trial enrichment. DISCUSSION:The preferred pathway is sequential: clinical evaluation and MRI establish context, validated plasma tests guide referral, and PET resolves uncertainty or refines staging when results may change management. This resource-aware integration improves diagnostic specificity and treatment decisions. Prospective implementation studies are needed to validate thresholds and equitable performance across diverse settings.

Fearful-expression recognition is vital for survival, yet how human amygdala subregions differentially support its distinct cognitive components, including rapid threat detection and fine-grained face processing, remains unclear. Here, we recorded intracranial EEG from lateral and medial amygdala in epilepsy patients performing an emotional face-matching task. Using multivariate decoding, time-frequency and directed-connectivity analyses with intracranial stimulation, we found that the lateral subregion exhibited early, fear-specific responses with higher decoding accuracy and elevated theta/alpha-band (4-12 Hz) power, and transmitted this fear-specific information to the medial subregion, which showed delayed and sustained activation. By contrast, the medial subregion encoded face-specific information at later stage in the 2-16 Hz band with superior decoding accuracy and power, and then relayed this information back to the lateral subregion to complete processing. Further, intracranial stimulation produced behaviorally selective effects, with lateral stimulation disrupting fear detection while medial stimulation accelerated face recognition. Together, our study reveals that functional specialization and frequency-specific dynamic interaction among human amygdala subregions underlie distinct cognitive components of fearful-expression recognition.

Alzheimer's disease (AD) is increasingly recognised as a disorder not only of cortical amyloid-β and tau deposition, but also of upstream neuromodulatory and clearance systems that shape when and where pathology emerges. Among these, the locus coeruleus (LC) noradrenergic nucleus and the brain's perivascular “glymphatic” network have attracted particular attention. In this review, we synthesise converging evidence that positions the LC–glymphatic interplay as a mechanistically relevant “axis” in AD, and evaluate two magnetic resonance imaging (MRI)-based proxies of this axis: neuromelanin-sensitive LC imaging and diffusion tensor image analysis along the perivascular space (DTI-ALPS). We first summarise neuropathological and experimental data demonstrating that the LC is an early and vulnerable tau node whose degeneration perturbs synaptic plasticity, neuroinflammation, sleep–wake regulation and vascular dynamics. The evidence base spans post-mortem neuropathology, animal mechanistic studies, and predominantly cross-sectional human MRI/PET observational cohorts, with fewer longitudinal studies and very limited interventional imaging datasets. We then review acquisition protocols, reliability and clinical findings for LC neuromelanin MRI, highlighting robust associations with cognitive performance and downstream tau burden. In parallel, we describe the physiological basis and methodological implementation of DTI-ALPS as an indirect marker of perivascular CSF–interstitial fluid transport, and collate studies linking reduced ALPS indices to amyloid/tau biomarkers, small vessel disease and cognitive decline. Integrating these literatures, we propose an in-vivo “LC–glymphatic axis” framework in which LC degeneration and impaired perivascular transport co-evolve and jointly influence AD risk and progression. We discuss how this framework can inform biomarker development, risk stratification and trial enrichment, and outline neuromodulatory strategies—such as transcutaneous vagus nerve stimulation and closed-loop slow-wave sleep enhancement—that could be used to experimentally engage this axis with LC MRI and ALPS as mechanism-proximal endpoints. Finally, we critically appraise methodological limitations, conceptual uncertainties and key gaps in longitudinal, multimodal and interventional evidence. Overall, imaging the LC–glymphatic axis offers a promising route to move beyond purely cortical markers and to test whether targeting upstream neuromodulation and clearance can contribute to genuine disease modification in AD.

Objective : Ventriculoperitoneal shunt (VPS) treats hydrocephalus effectively, but manual ventricular catheter placement has a high misplacement rate. This study assesses the feasibility, accuracy, and safety of robot-assisted VPS. Methods : A retrospective analysis was performed on the clinical data of 87 patients from 2022 to 2024, with 42 receiving robot-assisted VPS and 45 receiving conventional manual VPS. Logistic regression analysis was performed to identify risk factors affecting placement accuracy. Results : The robot-assisted cohort showed smaller bilateral frontal horn diameters and a lower Evans index (p<0.05). It achieved higher placement accuracy, required fewer puncture attempts, and had a lower postoperative complication rate (p<0.05). No significant difference was found in operation time (p>0.05). Logistic regression analysis confirmed robot-assistance as a key factor for accurate catheter placement (odds ratio, 6.52; p<0.001). Conclusion : Robot-assisted VPS achieves precise placement, reduces puncture attempts and complications, and does not increase time costs, confirming its clinical feasibility, accuracy, and safety.

BACKGROUND:Autism spectrum disorder (ASD) comprises a group of persistent neurodevelopmental conditions characterized by impairments in communication, restricted behavioral patterns, and social dysfunction. In severe cases, ASD can lead to self-injury or suicide, imposing a significant burden on individuals, families, and society. This study aimed to comprehensively assess the temporal, demographic, and regional patterns of ASD burden from 1990 to 2021; project future trends; and provide insights into potential causes and public health strategies. METHODS:Data on the incidence, prevalence, and disability-adjusted life years (DALYs) of ASD were extracted from the Global Burden of Disease (GBD) Study 2021. Temporal trends were evaluated using estimated annual percentage change (EAPC) and Bayesian age-period-cohort (BAPC) modeling. We further examined burden distribution by age, sex, region, and sociodemographic index (SDI). RESULTS:In 2021, an estimated 61.82 million individuals were living with ASD globally, with 1.16 million new cases and 11.54 million DALYs. The global age-standardized point prevalence, incidence, and DALY rates were 788.3, 18.8, and 147.6 per 100,000 population, respectively-representing increases of 2.0%, 5.2%, and 2.1% since 1990. Regionally, the highest age-standardized prevalence rate was observed in the High-income Asia Pacific region, while tropical Latin America had the lowest. At the national level, Japan recorded the highest age-standardized prevalence, whereas the Republic of Mauritius had the lowest. CONCLUSION:ASD poses a rising global public health challenge, with persistent regional disparities and underrecognized burden in adults and females. Current gaps in epidemiological surveillance, etiological understanding, and treatment capacity highlight the urgent need for greater governmental investment in ASD-related research, early detection strategies, and inclusive care systems.

High-grade gliomas—particularly glioblastoma (GBM)—remain refractory to standard-of-care surgery followed by chemoradiation, with a median overall survival of ~15 months. Oncolytic viruses (OVs), which selectively infect and lyse tumor cells while engaging antitumor immunity, offer a mechanistically distinct therapeutic modality. This review synthesizes clinical progress of OVs in GBM, with emphasis on oncolytic herpes simplex virus (oHSV) and coverage of other vectors (adenovirus, reovirus, Newcastle disease virus, vaccinia virus) across phase I–III trials, focusing on efficacy and safety. Key observations include the encouraging clinical trajectory of oHSV exemplars—T-VEC (approved for melanoma) and G47Δ (approved in Japan for recurrent GBM)—the multi-center exploration of the adenovirus DNX-2401 combined with programmed death-1 (PD-1) blockade, and the early-stage status of reovirus (pelareorep) and Newcastle disease virus programs. Emerging evidence indicates that oHSV therapy augments immune infiltration within the tumor microenvironment and alleviates immunosuppression, with synergy when combined with chemotherapy or immune checkpoint inhibitors. Persistent challenges include GBM’s inherently immunosuppressive milieu, limitations imposed by the blood–brain barrier, intrapatient viral delivery and biodistribution, and concerns about viral shedding. Future directions encompass programmable vector design, optimization of systemic delivery, biomarker-guided patient selection, and rational combination immunotherapy. Collectively, OVs represent a promising immunotherapeutic strategy in GBM; further gains will hinge on vector engineering and precision combinations to translate mechanistic promise into durable clinical benefit.

Human high-order thalamic nuclei activity is known to closely correlate with conscious states. However, it is not clear how those thalamic nuclei and thalamocortical interactions directly contribute to the transient process of human conscious perception. We simultaneously recorded stereoelectroencephalography data from the thalamic nuclei and prefrontal cortex (PFC), while patients with implanted electrodes performed a visual consciousness task. Compared with the ventral nuclei and PFC, the intralaminar and medial nuclei presented earlier and stronger consciousness-related activity. Transient thalamofrontal neural synchrony and cross-frequency coupling were both driven by the θ phase of the intralaminar and medial nuclei during conscious perception. The intralaminar and medial thalamic nuclei thus play a gate role to drive the activity of the PFC during the emergence of conscious perception.

Fearful-expression recognition is vital for survival, relying on rapid fear detection and fine-grained face encoding. However, how human amygdala subregions differentially implement these distinct cognitive components remains unclear. Here, we recorded intracranial EEG from lateral and medial amygdala in epilepsy patients performing an emotional face-matching task, and combined multivariate decoding, time-frequency and directed-connectivity analyses with intracranial stimulation. We found that the lateral subregion exhibited early, fear-specific theta/alpha-band (4-12 Hz) activity with higher decoding accuracy and directed transfer of fear-specific information to the medial subregion, which showed delayed and sustained activation. By contrast, the medial subregion encoded face-specific information at a later stage in the 2-16 Hz band with superior decoding accuracy, and then relayed this information back to the lateral subregion. Critically, intracranial stimulation yielded double-dissociable behavioural effects, with lateral stimulation disrupting early fear detection while medial stimulation accelerated neutral-face recognition. Together, our study delineates a hierarchically organized, temporally structured division of labour within the human amygdala and show that dynamic interactions underlie hierarchical processing of fearful expressions. Significance Statement Recognizing fearful expressions is critical for adaptive behavior, yet how human amygdala subregions support this complex process remains unclear. By recording and stimulating the amygdala directly in humans, we demonstrate that the lateral and medial amygdala function in a temporally structured hierarchical framework in which the lateral amygdala rapidly detects threats while the medial amygdala subsequently integrates detailed facial information. These findings extend our understanding of how the amygdala coordinates multiple aspects of fear processing, offering new insight into the neural mechanisms underlying human adaptive behavior. ### Competing Interest Statement The authors have declared no competing interest. Beijing Natural Science Foundation National Natural Science Foundation of China the Young Talent Project of Chinese PLA General Hospital the Innovation Incubation Project of Chinese PLA General Hospital for the Department of Neurosurgery Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning

Photoacoustic imaging (PAI), by combining high optical contrast with ultrasonic resolution, offers a promising noninvasive approach for dynamic monitoring of cerebral vasculature. However, transcranial PAI still faces significant challenges due to strong attenuation of both optical and acoustic signals by the skull. In this study, we propose a multi-wavelength photoacoustic tomography system and method for intracranial pressure (ICP) assessment, enabling visualization of cross-sectional structures of the middle cerebral artery (MCA) through the human temporal bone. By utilizing multi-wavelength excitation in the near-infrared-I (NIR-I) window, quantitative maps of blood oxygen saturation (𝐬𝐎_2) are reconstructed, and the relationship between oxygenation dynamics and ICP variations is established. Experimental results demonstrate that the proposed system can successfully capture dynamic 𝐬𝐎_2 fluctuations in the MCA despite skull attenuation, revealing its characteristic responses to ICP changes. This work provides a high-precision, noninvasive imaging tool for early stroke diagnosis, cerebral vascular function assessment, and neurointerventional guidance, highlighting the clinical translational potential of PAI in neuroscience.

Fearful-expression recognition is critical for adaptive responses to potential threats and relies on both rapid threat detection and fine-grained face encoding. Yet how human amygdala subregions differentially support these distinct cognitive components remains unclear. Here, we recorded intracranial EEG from lateral and medial amygdala in epilepsy patients performing an emotional face-matching task and combined multivariate decoding, time-frequency and directed-connectivity analyses with intracranial stimulation. The lateral amygdala exhibited early fear-specific responses, characterized by higher decoding accuracy and increased theta/alpha-band (4-12 Hz) power, and transmitted this fear-related information to the medial amygdala, which showed delayed and sustained activation. By contrast, the medial amygdala encoded face-specific information at later stages in the 2-16 Hz band with superior decoding accuracy and then relayed this information back to the lateral amygdala. Intracranial stimulation produced a double dissociation in behavior, with lateral amygdala stimulation disrupting fear detection, whereas medial amygdala stimulation selectively accelerated neutral-face recognition. Together, these findings reveal a temporal hierarchy in the human amygdala, whereby dynamic bidirectional interactions between subregions implement distinct components of fearful-expression recognition, providing a circuit-level framework for understanding social threat processing.

Photoacoustic imaging combines the high contrast of optical imaging with the deep penetration depth of ultrasonic imaging, showing great potential in cerebrovascular disease detection. However, the ultrasonic wave suffers strong attenuation and multi-scattering when it passes through the skull tissue, resulting in the distortion of the collected photoacoustic signal. In this paper, inspired by the principles of deep learning and non-line-of-sight imaging, we propose an image reconstruction framework named HDN (Hybrid Deep-learning and Non-line-of-sight), which consists of the signal extraction part and difference utilization part. The signal extraction part is used to correct the distorted signal and reconstruct an initial image. The difference utilization part is used to make further use of the signal difference between the distorted signal and corrected signal, reconstructing the residual image between the initial image and the target image. The test results on a photoacoustic digital brain simulation dataset show that compared with the traditional method (delay-and-sum) and deep-learning-based method (UNet), the HDN achieved superior performance in both signal correction and image reconstruction. Specifically for the structural similarity index, the HDN reached 0.661 in imaging results, compared to 0.157 for the delay-and-sum method and 0.305 for the deep-learning-based method.

In this paper, the research progress of surface-enhanced Raman spectroscopy (SERS) research in the nervous system in recent years is reviewed. Firstly, the current status of neurotransmitter testing is briefly introduced, and the advantages of SERS detection technology are proposed. Secondly, the development status of SERS technology for neurotransmitters is reviewed, such as monoamines and amino acids. Thirdly, the SERS used to detect neurological diseases are mainly introduced, and SERS based microdevices are further introduced. In addition, the diagnostic applications of SERS in malignant tumors of the nervous system are analyzed.

Objective To investigate the long-term efficacy of amygdala-hippocampus deep brain stimulation (AH - DBS) in treating refractory medial temporal lobe epilepsy (mTLE) and its impact on cognitive function. Methods Seven patients with refractory mTLE who were treated at The First Medical Center of Chinese PLA General Hospital from January 2014 to December 2018 were enrolled in this study. All 7 patients underwent AH -DBS. Seizure types, seizure frequency, and antiepileptic seizure medicine (ASM) usage were compared before and after surgery. Cognitive function was assessed using Wechsler Adult Intelligence Scale - Revised (WAIS - R). Post - operative stimulation parameters and surgery - related complications were recorded. Results Of the 7 patients, 4 patients received bilateral AH-DBS, 2 patients received left AH - DBS, and one patient received left AH - DBS combined with right anterior temporal lobectomy. There were 6 patients underwent the occipital approach, and one patient underwent the frontal approach. Only one patient experienced poor healing of the scalp incision, which healed after local skin grafting. The mean follow-up period was (73.00 ± 8.98) months. During the follow-up period, there were reductions in complex partial seizure (CPS) frequency [1.00 (0.00, 31.00) times per month vs. 2.00 (1.50, 60.00) times per month; Z = - 2.207, P = 0.027], secondary generalized tonic - clonic seizure (SGTCS) frequency [0.00 (0.00, 1.00) times per month vs. 2.00 (1.00, 3.00) times per month; Z = - 2.428, P = 0.015], and the total seizure frequency [1.00 (0.50, 31.00) times per month vs. 5.00 (2.50, 64.00) times per month; Z = - 2.366, P = 0.018]. However, there were no significant differences in the number of ASM types [1.00 (1.00, 2.00) types vs. 1.00 (1.00, 3.00) types; Z = - 1.633, P = 0.102] or WAIS-R [(85.50 ± 7.09) scores vs. (89.00 ± 9.47) scores; t = - 1.761, P = 0.078] before and after surgery. Conclusions As a novel anti - epileptic treatment method, AH-DBS can reduce the frequency of refractory mTLE without serious adverse events and has no significant impact on cognitive function.

Abstract Background Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. Methods This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive–compulsive disorder (OCD), depression, and quality of life, respectively. Results Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). Conclusions DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

Human high-order thalamic nuclei have been known to closely correlate with conscious states. However, given the great difference of conscious states and contents (conscious perception), it is nearly unknown how those thalamic nuclei and thalamocortical interactions directly contribute to the transient process of conscious perception. To address this question, we simultaneously recorded local field potentials (LFP) in the human intralaminar, medial and ventral thalamic nuclei as well as in the prefrontal cortex (PFC), while patients with implanted electrodes performing a visual consciousness task. Overall, compared to the ventral nuclei, intralaminar and medial nuclei showed earlier and stronger consciousness-related activity. Moreover, the transient thalamocortical neural synchrony and cross-frequency coupling were both driven by the theta phase of the intralaminar and medial nuclei during conscious perception. These results indicated that the intralaminar and medial thalamic nuclei, rather than the commonly believed PFC, play a decisive ‘gate’ role in conscious perception. Highlights 1. Intralaminar and medial thalamic nuclei showed earlier and stronger visual consciousness-related activity, comparing to the ventral nuclei. 2. Intralaminar and medial thalamic transiently drove the thalamocortical synchronization through theta (2-8Hz) phase modulation during the emergence of visual consciousness. 3. Theta phase of intralaminar and medial thalamic activity dynamically regulated the amplitude of PFC activity during the emergence of consciousness. 4. Intralaminar and medial thalamic nuclei showed more regulation on lateral PFC than on other PFC subregions during the emergence of consciousness. ### Competing Interest Statement The authors have declared no competing interest.

Background Precisely localizing the seizure onset zone (SOZ) is critical for focal epilepsy surgery. Existing methods mainly focus on high-frequency activities in stereo-electroencephalography, but often fail when seizures are not driven by high-frequency activities. Recognized as biomarkers of epileptic seizures, ictal spikes in SOZ induce epileptiform discharges in other brain regions. Based on this understanding, we aim to develop a universal algorithm to localize SOZ and investigate how ictal spikes within the SOZ induce seizures. Methods We proposed a novel metric called standard deviation of spike amplitude (SDSA) and utilized channel-averaged SDSA to describe seizure processes and detect seizures. By integrating SDSA values in specific intervals, the score for each channel located within SOZ was calculated. Channels with high SOZ scores were clustered as SOZ. The localization accuracy was asserted using area under the receiver operating characteristic (ROC) curve. Further, we analyzed early ictal signals from SOZ channels and investigated factors influencing their duration to reveal the seizure inducing conditions. Results We analyzed data from 15 patients with focal epilepsy. The channel-averaged SDSA successfully detected all 28 seizures without false alarms. Using SDSA integration, we achieved precise SOZ localization with an average area under ROC curve (AUC) of 0.96, significantly outperforming previous methods based on high-frequency activities. Further, we discovered that energy of ictal spikes in SOZ was concentrated at a specific frequency distributed in [6, 12 Hz]. Additionally, we found that the higher the energy per second in this frequency band, the faster ictal spikes could induce seizures. Conclusion The SDSA metric offered precise SOZ localization with robustness and low computational cost, making it suitable for clinical practice. By studying the propagation patterns of ictal spikes between the SOZ and non-SOZ, we suggest that ictal spikes from SOZ need to accumulate energy at a specific central frequency to induce epileptic spikes in non-SOZ, which may have significant implications for understanding the seizure onset pattern.

Abstract Background In recent years, the development of robotic neurosurgery has brought many benefits to patients, but there are few studies on the occurrence of surgical site infection (SSI) after robot-assisted stereoelectroencephalography (SEEG). The purpose of this study was to collect relevant data from robot-assisted SEEG over the past ten years and to analyze the influencing factors and economic burden of surgical site infection. Methods Basic and surgical information was collected for all patients who underwent robot-assisted SEEG from January 2014 to December 2023. Logistic regression was used to analyze the factors influencing SSI according to different subgroups (radiofrequency thermocoagulation or epilepsy resection surgery). Results A total of 242 subjects were included in this study. The risk of SSI in the epilepsy resection surgery group (18.1%) was 3.5 times greater than that in the radiofrequency thermocoagulation group (5.1%) (OR 3.49, 95% CI 1.39 to 9.05); this difference was statistically significant. SSI rates in the epilepsy resection surgery group were associated with shorter surgical intervals (≤ 9 days) and higher BMI (≥ 23 kg/m2) (6.1 and 5.2 times greater than those in the control group, respectively). Hypertension and admission to the intensive care unit (ICU) were risk factors for SSI in the radiofrequency thermocoagulation group. Patients with SSIs had $21,231 more total hospital costs, a 7-day longer hospital stay, and an 8-day longer postoperative hospital stay than patients without SSI. Conclusions The incidence of SSI in patients undergoing epilepsy resection after stereoelectroencephalography was higher than that in patients undergoing radiofrequency thermocoagulation. For patients undergoing epilepsy resection surgery, prolonging the interval between stereoelectroencephalography and epilepsy resection surgery can reduce the risk of SSI; At the same time, for patients receiving radiofrequency thermocoagulation treatment, it is not recommended to enter the ICU for short-term observation if the condition permits.

The integration of stereoelectroencephalography with therapeutic deep brain stimulation (DBS) holds immense promise as a viable approach for precise treatment of refractory disorders, yet it has not been explored in the domain of headache or pain management. Here, we implanted 14 electrodes in a patient with refractory migraine and integrated clinical assessment and electrophysiological data to investigate personalized targets for refractory headache treatment. Using statistical analyses and cross-validated machine-learning models, we identified high-frequency oscillations in the right nucleus accumbens as a critical headache-related biomarker. Through a systematic bipolar stimulation approach and blinded sham-controlled survey, combined with real-time electrophysiological data, we successfully identified the left dorsal anterior cingulate cortex as the optimal target for the best potential treatment. In this pilot study, the concept of the herein-proposed data-driven approach to optimizing precise and personalized treatment strategies for DBS may create a new frontier in the field of refractory headache and even pain disorders.