Utilization of psychiatry services in the emergency department following a terror event in Israel.

In October 2023, Israel sustained a massive terror attack, with 1,300 people murdered, over 240 kidnapped, and millions exposed to the horrors. This study's aim is to examine the profile of patients arriving to the emergency department (ED) for psychiatric services during the month following the attack, compared to a similar period the year prior. In this cohort study, we compared patients arriving to the ED of a large general hospital in the center of Tel Aviv for psychiatric services during the month post-attack with the previous year using t-tests and chi-square exams. In 2023, 256 patients arrived in the ED for psychiatric evaluation and/or treatment, 46 % more than in 2022. Of these, 64 % were examined due to symptoms related to the terror attack. In 2023, significantly fewer patients had a prior psychiatric diagnosis (68% vs. 89 %). Significantly more patients were diagnosed with acute stress reaction or acute stress disorder in the ED, compared to almost no such diagnoses in 2022 (14 % and 43% vs. 0 % and 1 %). Major terror incidents profoundly influence psychiatric ED visits. Planning efforts for major emergencies should be adapted accordingly.

Perception of emotionally incongruent cues: evidence for overreliance on body vs. face expressions in Parkinson's disease.

Individuals with Parkinson's disease (PD) may exhibit impaired emotion perception. However, research demonstrating this decline has been based almost entirely on the recognition of isolated emotional cues. In real life, emotional cues such as expressive faces are typically encountered alongside expressive bodies. The current study investigated emotion perception in individuals with PD (n = 37) using emotionally incongruent composite displays of facial and body expressions, as well as isolated face and body expressions, and congruent composite displays as a baseline. In addition to a group of healthy controls (HC) (n = 50), we also included control individuals with schizophrenia (SZ) (n = 30), who display, as in PD, similar motor symptomology and decreased emotion perception abilities. The results show that individuals with PD showed an increased tendency to categorize incongruent face-body combinations in line with the body emotion, whereas those with HC showed a tendency to classify them in line with the facial emotion. No consistent pattern for prioritizing the face or body was found in individuals with SZ. These results were not explained by the emotional recognition of the isolated cues, cognitive status, depression, or motor symptoms of individuals with PD and SZ. As real-life expressions may include inconsistent cues in the body and face, these findings may have implications for the way individuals with PD and SZ interpret the emotions of others.

Bridging language barriers in developing valid health policy research tools: insights from the translation and validation process of the SHEMESH questionnaire.

BACKGROUND: The use of research tools developed and validated in one cultural and linguistic context to another often faces challenges. One major challenge is poor performance of the tool in the new context. This potentially impact the legitimacy of health policy research conducted with informal adaptations of existing tools which have not been subjected to formal validation. Best practices exist to guide researchers in adapting and validating research tools effectively. We present here, as an extended example, our validation of the SHEMESH questionnaire ('Organizational Readiness to Change Assessment'; In Hebrew: 'SHE'elon Muchanut Ergunit le'SHinuy'), a Hebrew-language version of the Organizational Readiness to Change Assessment (ORCA). SHEMESH is tailored to support implementation science projects, whose aim is to promote a more rapid and complete adoption of evidence-based health policies and practices. METHODS: The SHEMESH included originally eleven questions from the Evidence (item 1-4) and Context (items 5-11) domains. We validated SHEMESH through the following steps: 1. Professional translation to Hebrew and discussion of the translation by multidisciplinary committee; 2. Back-translation into English by a different translator to detect discrepancies; 3. Eleven cognitive interviews with psychiatric emergency department physicians and nurses; and 4. Pilot testing and psychometric analyses, including Cronbach's alpha for subscales and factor analyses. RESULTS: Following translation and cognitive interviews, SHEMESH was administered to 222 psychiatrists and nurses. Pearson correlation showed significant and strong correlations of items 1-4 to the Evidence construct and items 6-11 to the Context construct. Item 5 did not correlate with the other items, and therefore was removed from the other psychometric procedures and eventually from the SHEMESH. Factor analysis with the remaining 10 items yielded two factors, which together explained a total of 69.7% of variance. Cronbach's Alpha scores for the two subscales were high (Evidence, 0.887, and Context, 0.852). CONCLUSIONS: This multi-step validation process of the SHEMESH questionnaire may serve as a comprehensive guideline for others who are willing to adapt research tools that were developed in other languages. Practically, SHEMESH has been validated for use in implementation science research projects in Israel.

Enabling Expedited Disposition of Emergencies Using Telepsychiatry in Israel: Protocol for a Hybrid Implementation Study.

BACKGROUND: Telepsychiatry is the use of virtual communication, such as a video link, to deliver mental health assessment, treatment, and follow-up. Previous studies have shown telepsychiatry to be feasible, accurate compared with in-person practice, and satisfying for psychiatrists and patients. Telepsychiatry has also been associated with reduced waiting times for evaluation and, in some studies, lower admission rates. However, most previous studies focused on using telepsychiatry in community settings and not on involuntary admission. OBJECTIVE: The aim of this study is to examine the effectiveness and implementation process of patient assessment for involuntary admissions in the psychiatric emergency department (ED) using a video link. METHODS: This type 1 hybrid implementation study will examine telepsychiatry effectiveness and the implementation process, by comparing telepsychiatry (n=240) with historical controls who had a face-to-face evaluation (n=240) during the previous, usual care period in 5 psychiatric EDs in Israel. A temporary waiver of the standing policy requiring in-person evaluations only, for the purpose of research, was obtained from the Israeli Ministry of Health. During the telepsychiatry phase, clinical staff and patients will join a video call from the ED, while the attending physician will log in elsewhere. The Promoting Action on Research Implementation in Health Services (PARIHS) framework will guide the evaluation of the telepsychiatry implementation process in the ED. PARIHS has the following 3 constructs: (1) evidence: staff's opinions regarding the innovation's viability and practicality, their satisfaction levels with its use, and patients' perceptions of the change; (2) context: level of approval of new strategies in the ED, decision-making processes, and the manner in which clinical teams converse and work together; (3) facilitation: adequacy of the facilitation efforts using champions reports. Primary clinical outcomes include ED length of stay and violent incidents obtained from medical records. RESULTS: This study received Helsinki approval from the Ethics Committee of Abarbanel Mental Health Center (174; March 13, 2023), Jerusalem Mental Health Center (22-21; November 6, 2022), Lev-Hasharon Mental Health Medical Center (LH12023; February 12, 2023), Tel-Aviv Medical Center (TLV-22-0656; January 3, 2023), and Sha'ar Menashe (1-4-23; April 18, 2023). Data collection began in July 2023 in 2 study sites and will begin soon at the others. CONCLUSIONS: Telepsychiatry could have significant benefits for patients in the psychiatric ED. Examining telepsychiatry effectiveness in the ED, in addition to identifying the facilitators and barriers of implementing it in different emergency settings, will facilitate better policy decisions regarding its implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT05771545; https://clinicaltrials.gov/study/NCT05771545. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49405.

Tuned to Tremor: Increased Sensitivity of Cortico-Basal Ganglia Neurons to Tremor Frequency in the MPTP Nonhuman Primate Model of Parkinson's Disease.

Rest tremor is one of the most prominent clinical features of Parkinson's disease (PD). Here, we hypothesized that cortico-basal ganglia neurons tend to fire in a pattern that matches PD tremor frequency, suggesting a resonance phenomenon. We recorded spiking activity in the primary motor cortex (M1) and globus pallidus external segment of 2 female nonhuman primates, before and after parkinsonian state induction with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The arm of nonhuman primates was passively rotated at seven different frequencies surrounding and overlapping PD tremor frequency. We found entrainment of the spiking activity to arm rotation and a significant sharpening of the tuning curves in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine state, with a peak response at frequencies that matched the frequency of PD tremor. These results reveal increased sensitivity of the cortico-basal ganglia network to tremor frequency and could indicate that this network acts not only as a tremor switch but is involved in setting its frequency.SIGNIFICANCE STATEMENT Tremor is a prominent clinical feature of Parkinson's disease; however, its underlying pathophysiology is still poorly understood. Using electrophysiological recordings of single cortico-basal ganglia neurons before and after the induction of a parkinsonian state, and in response to passive arm rotation, this study reports increased sensitivity to tremor frequency in Parkinson's disease. We found sharpening of the population tuning to the midrange of the tested frequencies (1-13.3 Hz) in the healthy state that further increased in the parkinsonian state. These results hint at the increased frequency-tuned sensitivity of cortico-basal ganglia neurons and suggest that they tend to resonate with the tremor.

When radical uncertainty is too much: Clinical aspects of Conviction Narrative Theory.

We propose extrapolating Conviction Narrative Theory (CNT) to clinical psychology and psychiatry. We demonstrate how CNT principles may benefit assessment, therapy, and possibly even modify public health views of neuropsychiatric disorders. Our commentary focuses on hoarding disorder as a model, elaborates on discrepancies in the scientific literature and suggests how the CNT may resolve them.

The Clinical and Economic Burden of Tardive Dyskinesia in Israel: Real-World Data Analysis.

PURPOSE/BACKGROUND: Tardive dyskinesia (TD) is a hyperkinetic movement disorder caused by exposure to dopamine-receptor blockers. Data on TD burden in Israel are scarce. This analysis assesses the clinical and economic burden of TD in Israeli patients. METHODS/PROCEDURES: This retrospective analysis used a national health plan database (Maccabi Healthcare Services), representing 25% of the Israeli population. The study included adults alive at index date with an International Classification of Diseases, Ninth Revision, Clinical Modification TD diagnosis before 2018 and more than or equal to 1-year enrollment before diagnosis. Tardive dyskinesia patients were matched to non-TD patients (1:3) by underlying psychiatric condition, birth year, and sex. Treatment patterns and 2018 annual health care resource utilization and costs were assessed. FINDINGS/RESULTS: Of 454 TD patients alive between 2013 and 2018, 333 alive on January 1, 2018, were matched to 999 non-TD patients. At baseline, TD patients had lower socioeconomic status and higher proportion of chronic kidney disease and antipsychotic medication use; all analyses were adjusted accordingly. Tardive dyskinesia patients had significantly more visits to general physicians, neurologists, psychiatrists, physiotherapists, and emergency departments versus non-TD patients (all P < 0.05). Tardive dyskinesia patients also had significantly longer hospital stays than non-TD patients ( P = 0.003). Total healthcare and medication costs per patient were significantly higher in the TD versus non-TD population (US $11,079 vs US $7145, P = 0.018). IMPLICATIONS/CONCLUSIONS: Israeli TD patients have higher clinical and economic burden than non-TD patients. Understanding real-world health care resource utilization and costs allows clinicians and decision makers to quantify TD burden and prioritize resources for TD patients' treatment.

Perceiving Dynamic Emotions Expressed Simultaneously in the Face and Body Minimizes Perceptual Differences Between Young and Older Adults.

OBJECTIVES: It is commonly argued that older adults show difficulties in standardized tasks of emotional expression perception, yet most previous works relied on classic sets of static, decontextualized, and stereotypical facial expressions. In real life, facial expressions are dynamic and embedded in a rich context, 2 key factors that may aid emotion perception. Specifically, body language provides important affective cues that may disambiguate facial movements. METHOD: We compared emotion perception of dynamic faces, bodies, and their combination in a sample of older (age 60-83, n = 126) and young (age 18-30, n = 124) adults. We used the Geneva Multimodal Emotion Portrayals set, which includes a full view of expressers' faces and bodies, displaying a diverse range of positive and negative emotions, portrayed dynamically and holistically in a nonstereotypical, unconstrained manner. Critically, we digitally manipulated the dynamic cue such that perceivers viewed isolated faces (without bodies), isolated bodies (without faces), or faces with bodies. RESULTS: Older adults showed better perception of positive and negative dynamic facial expressions, while young adults showed better perception of positive isolated dynamic bodily expressions. Importantly, emotion perception of faces with bodies was comparable across ages. DISCUSSION: Dynamic emotion perception in young and older adults may be more similar than previously assumed, especially when the task is more realistic and ecological. Our results emphasize the importance of contextualized and ecological tasks in emotion perception across ages.

Comparable reliability and acceptability of telepsychiatry and face-to-face psychiatric assessments in the emergency room setting.

OBJECTIVE: This study aims to compare the reliability and acceptability of psychiatric interviews using telepsychiatry and face-to-face modalities in the emergency room setting. METHODS: In this prospective observational feasibility study, psychiatric patients (n = 38) who presented in emergency rooms between April and June 2020, went through face-to-face and videoconference telepsychiatry interviews in a non-randomised varying order. Interviewers and a senior psychiatry resident who observed both interviews determined diagnosis, recommended disposition and indication for involuntary admission. Patients and psychiatrists completed acceptability post-assessment surveys. RESULTS: Agreement between raters on recommended disposition and indication for involuntary admission as measured by Cohen's kappa was 'strong' to 'almost perfect' (0.84/0.81, 0.95/0.87 and 0.89/0.94 for face-to-face vs. telepsychiatry, observer vs. face-to-face and observer vs. telepsychiatry, respectively). Partial agreement between the raters on diagnosis was 'strong' (Cohen's kappa of 0.81, 0.85 and 0.85 for face-to-face vs. telepsychiatry, observer vs. face-to-face and observer vs. telepsychiatry, respectively).Psychiatrists' and patients' satisfaction rates, and psychiatrists' perceived certainty rates, were comparably high in both face-to-face and telepsychiatry groups. CONCLUSIONS: Telepsychiatry is a reliable and acceptable alternative to face-to-face psychiatric assessments in the emergency room setting. Implementing telepsychiatry may improve the quality and accessibility of mental health services.Key pointsTelepsychiatry and face-to-face psychiatric assessments in the emergency room setting have comparable reliability.Patients and providers report a comparable high level of satisfaction with telepsychiatry and face-to-face modalities in the emergency room setting.Providers report a comparable level of perceived certainty in their clinical decisions based on telepsychiatry and face-to-face psychiatric assessments in the emergency room setting.

Deep Brain Stimulation Can Differentiate Subregions of the Human Subthalamic Nucleus Area by EEG Biomarkers.

Introduction: Precise lead localization is crucial for an optimal clinical outcome of subthalamic nucleus (STN) deep brain stimulation (DBS) treatment in patients with Parkinson's disease (PD). Currently, anatomical measures, as well as invasive intraoperative electrophysiological recordings, are used to locate DBS electrodes. The objective of this study was to find an alternative electrophysiology tool for STN DBS lead localization. Methods: Sixty-one postoperative electrophysiology recording sessions were obtained from 17 DBS-treated patients with PD. An intraoperative physiological method automatically detected STN borders and subregions. Postoperative EEG cortical activity was measured, while STN low frequency stimulation (LFS) was applied to different areas inside and outside the STN. Machine learning models were used to differentiate stimulation locations, based on EEG analysis of engineered features. Results: A machine learning algorithm identified the top 25 evoked response potentials (ERPs), engineered features that can differentiate inside and outside STN stimulation locations as well as within STN stimulation locations. Evoked responses in the medial and ipsilateral fronto-central areas were found to be most significant for predicting the location of STN stimulation. Two-class linear support vector machine (SVM) predicted the inside (dorso-lateral region, DLR, and ventro-medial region, VMR) vs. outside [zona incerta, ZI, STN stimulation classification with an accuracy of 0.98 and 0.82 for ZI vs. VMR and ZI vs. DLR, respectively, and an accuracy of 0.77 for the within STN (DLR vs. VMR)]. Multiclass linear SVM predicted all areas with an accuracy of 0.82 for the outside and within STN stimulation locations (ZI vs. DLR vs. VMR). Conclusions: Electroencephalogram biomarkers can use low-frequency STN stimulation to localize STN DBS electrodes to ZI, DLR, and VMR STN subregions. These models can be used for both intraoperative electrode localization and postoperative stimulation programming sessions, and have a potential to improve STN DBS clinical outcomes.

Machine learning-based personalized subthalamic biomarkers predict ON-OFF levodopa states in Parkinson patients.

Objective.Adaptive deep brain stimulation (aDBS) based on subthalamic nucleus (STN) electrophysiology has recently been proposed to improve clinical outcomes of DBS for Parkinson's disease (PD) patients. Many current models for aDBS are based on one or two electrophysiological features of STN activity, such as beta or gamma activity. Although these models have shown interesting results, we hypothesized that an aDBS model that includes many STN activity parameters will yield better clinical results. The objective of this study was to investigate the most appropriate STN neurophysiological biomarkers, detectable over long periods of time, that can predict OFF and ON levodopa states in PD patients.Approach.Long-term local field potentials (LFPs) were recorded from eight STNs (four PD patients) during 92 recording sessions (44 OFF and 48 ON levodopa states), over a period of 3-12 months. Electrophysiological analysis included the power of frequency bands, band power ratio and burst features. A total of 140 engineered features was extracted for 20 040 epochs (each epoch lasting 5 s). Based on these engineered features, machine learning (ML) models classified LFPs as OFF vs ON levodopa states.Main results.Beta and gamma band activity alone poorly predicts OFF vs ON levodopa states, with an accuracy of 0.66 and 0.64, respectively. Group ML analysis slightly improved prediction rates, but personalized ML analysis, based on individualized engineered electrophysiological features, were markedly better, predicting OFF vs ON levodopa states with an accuracy of 0.8 for support vector machine learning models.Significance.We showed that individual patients have unique sets of STN neurophysiological biomarkers that can be detected over long periods of time. ML models revealed that personally classified engineered features most accurately predict OFF vs ON levodopa states. Future development of aDBS for PD patients might include personalized ML algorithms.

A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.

Interrupting traumatic memories in the emergency department: a randomized controlled pilot study.

BACKGROUND: The hours immediately following a traumatic event may present a window of opportunity to interrupt the consolidation of memories of the traumatic event, and this may prevent PTSD development. This theory has been validated in a series of analogue studies, showing that a visuo-spatial task reduces intrusive memories, however clinical studies are scarce. OBJECTIVE: This pilot RCT examined the use of a semi-immersive Virtual Reality visuospatial task, as an intervention to interrupt memory consolidation, in the Emergency Department (ED) in the immediate hours following a traumatic event. We hypothesised that participants who had received the intervention would present with lower levels of PTSD symptoms than the control group who received no intervention. METHOD: Seventy-seven adult survivors of traumatic events, meeting study criteria, were recruited in the ED of a Level III Trauma Centre. Survivors arrived at the ED less than one hour, on average, after the trauma. After signing informed consent, participants were randomized to the SnowWorld intervention or control group. Both groups completed self-report questionnaires, and the intervention group used SnowWorld for up to 10 minutes. RESULTS: No significant differences between the intervention and control groups were found regarding PTSD symptom levels two weeks and six months following the traumatic event. CONCLUSIONS: These results add to the growing literature examining the use of a concurrent task to reduce intrusions following a traumatic event. In contrast to previous clinical studies, this study did not show significant group differences; however, it replicates an analogue study that used a specifically developed app. Further studies are needed to elucidate possible reasons for these conflicting results.

Antecedentes: Las horas que siguen inmediatamente a un evento traumático podrían presentar una ventana de oportunidad para interrumpir la consolidación de las memorias del evento traumático, y esto podría prevenir el desarrollo del TEPT. Esta teoría ha sido validada en una serie de estudios análogos, mostrando que una tarea viso-espacial reduce las memorias intrusivas; los estudios clínicos son escasos.Objetivo: este ensayo controlado aleatorio (RCT en su sigla en inglés) piloto examinó el uso de una tarea viso-espacial de Realidad Virtual semi-inmersa como una intervención para interrumpir la memoria de consolidación en el Departamento de Emergencia, en las horas siguientes a un evento traumático. Hipotetizamos que al seguimiento aquellos que habían recibido la intervención presentarían niveles más bajos de los síntomas del TEPT que el grupo control.Método: Fueron reclutados en el Departamento de Emergencia (ED en su sigla en inglés) de un Centro de Trauma de Nivel III, 77 sobrevivientes adultos de eventos traumáticos, cumpliendo los criterios del estudio; los sobrevivientes llegaron al ED en promedio menos de una hora luego del trauma. Luego de firmar el consentimiento informado, fueron aleatorizados a la intervención SnowWorld o al grupo control. Ambos grupos completaron cuestionarios de auto-reporte, y el primer grupo usó SnowWorld por un máximo de 10 minutos.Resultados: No se encontraron diferencias significativas entre los grupos de estudio en los niveles de los síntomas de TEPT dos semanas y seis meses luego del evento traumático.Conclusiones: Este estudio no replicó los estudios clínicos y análogos previos. Esto puede deberse a las diferencias metodológicas, y los estudios futuros deberían tomarlos en cuenta.

A Novel Integrative Psychotherapy for Psychogenic Nonepileptic Seizures Based on the Biopsychosocial Model: A Retrospective Pilot Outcome Study.

BACKGROUND: Psychogenic nonepileptic seizures (PNES) represent one of the most sizable treatment challenges in neuropsychiatry. Although the underlying mechanism is far from being understood, several interventions have been suggested. However, patients with comorbid psychiatric diagnoses and epilepsy are excluded from most intervention studies. OBJECTIVE: To To present a within-group posttreatment vs pretreatment study representing the retrospective clinical results of an integrative psychotherapy model. METHODS: We present the clinical results of 22 patients with PNES diagnosed in an epilepsy center and treated in our neuropsychiatry clinic using an integrative rehabilitative psychotherapy. Therapy included presenting the diagnosis, psychoeducation, seizure reduction behavioral techniques, and coping with past and present stressors. Insomuch as integrative biopsychosocial psychotherapy is based on an individualized treatment protocol for each patient, treatment was individualized and case specific. RESULTS: By the end of treatment, 36% of patients had become seizure free and a further 54% achieved a major seizure reduction (reduction of more than 70%). Seventy-two percent of patients kept at least 70% seizure reduction at follow-up. Global Assessment of Functioning scores improved from a mean of 43.09 to a mean of 72.81 at the end of treatment and 69.72 at follow-up. In addition, we present 3 case descriptions that emphasize the individualized nature of psychotherapeutic decisions. CONCLUSIONS: Our results support the feasibility and effectiveness of biopsychosocial based integrative psychotherapy for PNES and set principles for future treatment and prospective clinical trials in the field of individualized psychotherapy.

Independently together: subthalamic theta and beta opposite roles in predicting Parkinson's tremor.

Tremor is a core feature of Parkinson's disease and the most easily recognized Parkinsonian sign. Nonetheless, its pathophysiology remains poorly understood. Here, we show that multispectral spiking activity in the posterior-dorso-lateral oscillatory (motor) region of the subthalamic nucleus distinguishes resting tremor from the other Parkinsonian motor signs and strongly correlates with its severity. We evaluated microelectrode-spiking activity from the subthalamic dorsolateral oscillatory region of 70 Parkinson's disease patients who underwent deep brain stimulation surgery (114 subthalamic nuclei, 166 electrode trajectories). We then investigated the relationship between patients' clinical Unified Parkinson's Disease Rating Scale score and their peak theta (4-7 Hz) and beta (13-30 Hz) powers. We found a positive correlation between resting tremor and theta activity (r = 0.41, P < 0.01) and a non-significant negative correlation with beta activity (r = -0.2, P = 0.5). Hypothesizing that the two neuronal frequencies mask each other's relationship with resting tremor, we created a non-linear model of their proportional spectral powers and investigated its relationship with resting tremor. As hypothesized, patients' proportional scores correlated better than either theta or beta alone (r = 0.54, P < 0.001). However, theta and beta oscillations were frequently temporally correlated (38/70 patients manifested significant positive temporal correlations and 1/70 exhibited significant negative correlation between the two frequency bands). When comparing theta and beta temporal relationship (r θ ß) to patients' resting tremor scores, we found a significant negative correlation between the two (r = -0.38, P < 0.01). Patients manifesting a positive correlation between the two bands (i.e. theta and beta were likely to appear simultaneously) were found to have lower resting tremor scores than those with near-zero correlation values (i.e. theta and beta were likely to appear separately). We therefore created a new model incorporating patients' proportional theta-beta power and r θ ßscores to obtain an improved neural correlate of resting tremor (r = 0.62, P < 0.001). We then used the Akaike and Bayesian information criteria for model selection and found the multispectral model, incorporating theta-beta proportional power and their correlation, to be the best fitting model, with 0.96 and 0.89 probabilities, respectively. Here we found that as theta increases, beta decreases and the two appear separately-resting tremor is worsened. Our results therefore show that theta and beta convey information about resting tremor in opposite ways. Furthermore, the finding that theta and beta coactivity is negatively correlated with resting tremor suggests that theta-beta non-linear scale may be a valuable biomarker for Parkinson's resting tremor in future adaptive deep brain stimulation techniques.

Movement context modulates neuronal activity in motor and limbic-associative domains of the human parkinsonian subthalamic nucleus.

The subthalamic nucleus (STN), a preferred target for treating movement disorders, has a crucial role in inhibition and execution of movement. To better understand the mechanism of movement regulation in the STN of Parkinson's disease patients, we compared the same movement with different context, facilitation vs. inhibition context. We recorded subthalamic multiunit activity intra-operatively while parkinsonian patients (off medications, n = 43 patients, 173 recording sites) performed increasingly complex oddball paradigms with frequent and deviant tones: first, passive listening to tone series with no movement ('None-Go' task, n = 7, 28 recording sites); second, pressing a button after every tone ('All-Go' task, n = 7, 26 recording sites); and third, pressing a button only for frequent tones, thus adding inhibition of movement following deviant tones ('Go-NoGo' task, n = 29, 119 recording sites). The STN responded mainly to movement-involving tasks. In the limbic-associative STN, evoked response to the deviant tone (inhibitory cue) was not significantly different between the Go-NoGo and the All-Go task. However, the evoked response to the frequent tone (go cue) in the Go-NoGo task was significantly reduced. The reduction was mainly prominent in the negative component of the evoked response amplitude aligned to the press. Successful movement inhibition was correlated with higher baseline activity. We suggest that the STN in Parkinson's disease patients adapts to movement inhibition context by selectively decreasing the amplitude of neuronal activity. Thus, the STN enables movement inhibition not by increasing responses to the inhibitory cue but by reducing responses to the release cue. The negative component of the evoked response probably facilitates movement and a higher baseline activity enables successful inhibition of movement. These discharge modulations were found in the ventromedial, non-motor domain of the STN and therefore suggest a significant role of the limbic- associative STN domains in movement planning and in global movement regulation.

Theta-alpha oscillations characterize emotional subregion in the human ventral subthalamic nucleus.

BACKGROUND: Therapeutic outcomes of STN-DBS for movement and psychiatric disorders depend on electrode location within the STN. Electrophysiological and functional mapping of the STN has progressed considerably in the past years, identifying beta-band oscillatory activity in the dorsal STN as a motor biomarker. It also has been suggested that STN theta-alpha oscillations, involved in impulse control and action inhibition, have a ventral source. However, STN local field potential mapping of motor, associative, and limbic areas is often limited by poor spatial resolution. OBJECTIVES: Providing a high-resolution electrophysiological map of the motor, associative and limbic anatomical sub-areas of the subthalamic nucleus. METHODS: We have analyzed high-spatial-resolution STN microelectrode electrophysiology recordings of PD patients (n = 303) that underwent DBS surgery. The patients' STN intraoperative recordings of spiking activity (933 electrode trajectories) were combined with their imaging data (n = 83 patients, 151 trajectories). RESULTS: We found a high theta-alpha (7-10 Hz) oscillatory area, located near the STN ventromedial border in 29% of the PD patients. Theta-alpha activity in this area has higher power and lower central frequency in comparison to theta-alpha activity in more dorsal subthalamic areas. When projected on the DISTAL functional atlas, the theta-alpha oscillatory area overlaps with the STN limbic subarea. CONCLUSIONS: We suggest that theta-alpha oscillations can serve as an electrophysiological marker for the ventral subthalamic nucleus limbic subarea. Therefore, theta-alpha oscillations can guide optimal electrode placement in neuropsychiatric STN-DBS procedures and provide a reliable biomarker input for future closed-loop DBS device. © 2019 International Parkinson and Movement Disorder Society.

A Real-Life Search for the Optimal Set of Conversion Factors to Levodopa-Equivalent-Dose in Parkinson's Disease Patients on Polytherapy.

BACKGROUND: A wide variety of conversion factors for a levodopa-equivalent-dose (LED) have been proposed for each Parkinson's disease (PD) medication. The currently-used set of conversion factors is based on studies that relied on subjective experience or theoretical assumptions. This set was never validated in patients receiving polytherapy. OBJECTIVES: To use real-life data to identify an optimal set of conversion factors independent of prior assumptions regarding clinical efficacy of different medications. METHODS: Retrospective analysis of data from 206 cognitively-preserved patients with advanced PD receiving polytherapy before deep brain stimulation (DBS) surgery. A nonlinear automated problem solver was used to find a set of conversion factors that, when applied, minimized the coefficient of variation of LEDs in a relatively homogenous cohort of patients. RESULTS: Independent and model-free evaluation of a wide range of possible sets of conversion factors to LED suggested a set of normalized conversion factors for immediate release levodopa (1.00), controlled release levodopa (0.88), and amantadine (1.23). A minimal clinical benefit of entacapone was observed for patients with motor fluctuations. Our analysis could not detect conversion factors for dopamine agonists and MAO-B inhibitors, possibly because their clinical contribution when added to levodopa is limited. CONCLUSIONS: Independent from previous studies and prior assumptions we show that the currently-used LED conversion factors for immediate release levodopa, controlled release levodopa and amantadine are largely correct and that dopamine agonists, MAO-B inhibitors and entacapone, given in addition to levodopa, have little additional clinical value for PD patients with motor fluctuations.

Real-time machine learning classification of pallidal borders during deep brain stimulation surgery.

OBJECTIVE: Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) in patients with Parkinson's disease and dystonia improves motor symptoms and quality of life. Traditionally, pallidal borders have been demarcated by electrophysiological microelectrode recordings (MERs) during DBS surgery. However, detection of pallidal borders can be challenging due to the variability of the firing characteristics of neurons encountered along the trajectory. MER can also be time-consuming and therefore costly. Here we show the feasibility of real-time machine learning classification of striato-pallidal borders to assist neurosurgeons during DBS surgery. APPROACH: An electrophysiological dataset from 116 trajectories of 42 patients consisting of 11 774 MER segments of background spiking activity in five classes of disease was used to train the classification algorithm. The five classes included awake Parkinson's disease patients, as well as awake and lightly anesthetized genetic and non-genetic dystonia patients. A machine learning algorithm was designed to provide prediction of the striato-pallidal borders, based on hidden Markov models (HMMs) and the L1-distance measure in normalized root mean square (NRMS) and power spectra of the MER. We tested its performance prospectively against the judgment of three electrophysiologists in the operating rooms of three hospitals using newly collected data. MAIN RESULTS: The awake and the light anesthesia dystonia classes could be merged. Using MER NRMS and spectra, the machine learning algorithm was on par with the performance of the three electrophysiologists across the striatum-GPe, GPe-GPi, and GPi-exit transitions for all disease classes. SIGNIFICANCE: Machine learning algorithms enable real-time GPi navigation systems to potentially shorten the duration of electrophysiological mapping of pallidal borders, while ensuring correct pallidal border detection.

Memory and motor control in patients with psychogenic nonepileptic seizures.

Psychogenic nonepileptic seizures (PNES) are of the most elusive phenomena in epileptology. Patients with PNES present episodes resembling epileptic seizures in their semiology yet lacking the underlying epileptic brain activity. These episodes are assumed to be related to psychological distress from past trauma, yet the underlying mechanism of this manifestation is still unknown. Using resting-state functional magnetic resonance imaging (fMRI), we investigated functional connectivity changes within and between large-scale brain networks in 9 patients with PNES, compared with a group of 13 age- and gender-matched healthy controls. Functional magnetic resonance imaging analyses identified functional connectivity disturbances between the medial temporal lobe (MTL) and the sensorimotor cortex and between the MTL and ventral attention networks in patients with PNES. Within network connectivity reduction was found within the visual network. Our findings suggest that PNES relate to changes in connectivity in between areas that are involved in memory processing and motor activity and attention control. These results may shed new light on the way by which traumatic memories may relate to PNES.