Randomized clinical trial of deep brain stimulation for poststroke pain.

OBJECTIVE: The experience with deep brain stimulation (DBS) for pain is largely based on uncontrolled studies targeting the somatosensory pathways, with mixed results. We hypothesized that targeting limbic neural pathways would modulate the affective sphere of pain and alleviate suffering. METHODS: We conducted a prospective, double-blinded, randomized, placebo-controlled, crossover study of DBS targeting the ventral striatum/anterior limb of the internal capsule (VS/ALIC) in 10 patients with poststroke pain syndrome. One month after bilateral DBS, patients were randomized to active DBS or sham for 3 months, followed by crossover for another 3-month period. The primary endpoint was a ≥50% improvement on the Pain Disability Index in 50% of patients with active DBS compared to sham. This 6-month blinded phase was followed by an 18-month open stimulation phase. RESULTS: Nine participants completed randomization. Although this trial was negative for its primary and secondary endpoints, we did observe significant differences in multiple outcome measures related to the affective sphere of pain (eg, Montgomery-Åsberg Depression Rating Scale, Beck Depression Inventory, Affective Pain Rating Index of the Short-Form McGill Pain Questionnaire). Fourteen serious adverse events were recorded and resolved. INTERPRETATION: VS/ALIC DBS to modulate the affective sphere of pain represents a paradigm shift in chronic pain management. Although this exploratory study was negative for its primary endpoint, VS/ALIC DBS demonstrated an acceptable safety profile and statistically significant improvements on multiple outcome measures related to the affective sphere of pain. Therefore, we believe these results justify further work on neuromodulation therapies targeting the affective sphere of pain. Ann Neurol 2017;81:653-663.

Cognitive outcome after ventral capsule/ventral striatum stimulation for treatment-resistant major depression.

BACKGROUND: We report the neuropsychological outcome of 25 patients with treatment-resistant major depressive disorder (TRD) who participated in an Institutional Review Board (IRB)-approved randomised double-blind trial comparing active to sham deep brain stimulation (DBS) in the anterior limb of the ventral capsule/ventral striatum (VC/VS). METHODS: Participants were randomised to active (n=12) versus sham (n=13) DBS for 16 weeks. Data were analysed at the individual and group levels. Group differences were analysed using repeated measures ANOVAs. Relationships between depression severity and cognition were examined using partial correlations. The false discovery rate method controlled for multiple analyses. RESULTS: No significant interactions comparing active versus sham stimulation over time were evident. Change in depression was unrelated to change in neuropsychological measures. Twenty patients declined by ≥1 SD on at least one measure (41.3% of declines occurred in active group participants; 63.0% in older participants regardless of stimulation status). Twenty-two patients exhibited improvements >1 SD on neuropsychological measures (47.7% in the active group; 63.1% in younger participants). CONCLUSIONS: These data suggest that VC/VS DBS in patients with TRD does not significantly affect neuropsychological function. Age at surgery, regardless of stimulation status, may be related to cognitive outcome at the individual patient level. TRIAL REGISTRATION NUMBER: NCT00837486; Results.

Global cognitive scores do not predict outcome after subthalamic nucleus deep brain stimulation.

BACKGROUND: Presence of dementia is a contraindication for DBS treatment of Parkinson's disease. Recent evidence suggests that borderline cognitive function, as measured with a common screening measure, the Mattis Dementia Rating Scale, has a negative impact on quality of life (QoL) after DBS of the STN. METHODS: We attempted to replicate and extend this finding in a larger group of patients with a wider range of preoperative global cognitive performance. RESULTS: Our data indicate that performance on the screening measure is not associated with QoL or medical outcomes, even with scores well below the cutoff for identifying dementia. CONCLUSIONS: This cognitive screening measure lacks sufficient sensitivity to warrant its use in predicting which patients will show QoL benefit from DBS.

Neuropsychological outcome after deep brain stimulation in the ventral capsule/ventral striatum for highly refractory obsessive-compulsive disorder or major depression.

BACKGROUND: Deep brain stimulation (DBS) has shown promise as a treatment for severe, highly treatment-refractory obsessive-compulsive disorder (OCD) or major depressive disorder (MDD). We describe the neuropsychological outcome in 21 patients (10 OCD and 11 MDD) who received DBS in the anterior limb of the internal capsule/ventral striatum (VC/VS). METHODS: All patients completed a preoperative and postoperative neuropsychological battery. Average duration of DBS stimulation was 8.91 months (SD = 4.63) at the time of follow-up testing. Data were analyzed using practice-effect-corrected change scores. RESULTS: No significant cognitive declines were seen. There were significant improvements in prose passage recall after chronic DBS. The cognitive improvements were not related to change in severity of OCD, depression or global impairment. CONCLUSIONS: This preliminary study suggests that VC/VS DBS does not result in cognitive declines. The observations that verbal memory improved are consistent with current theories on the role of the VS in the memory, but require replication in larger studies.

Corrigendum: Does personality change follow deep brain stimulation in Parkinson's disease patients?

[This corrects the article DOI: 10.3389/fpsyg.2021.643277.].

Future directions in psychiatric neurosurgery: Proceedings of the 2022 American Society for Stereotactic and Functional Neurosurgery meeting on surgical neuromodulation for psychiatric disorders.

OBJECTIVE: Despite advances in the treatment of psychiatric diseases, currently available therapies do not provide sufficient and durable relief for as many as 30-40% of patients. Neuromodulation, including deep brain stimulation (DBS), has emerged as a potential therapy for persistent disabling disease, however it has not yet gained widespread adoption. In 2016, the American Society for Stereotactic and Functional Neurosurgery (ASSFN) convened a meeting with leaders in the field to discuss a roadmap for the path forward. A follow-up meeting in 2022 aimed to review the current state of the field and to identify critical barriers and milestones for progress. DESIGN: The ASSFN convened a meeting on June 3, 2022 in Atlanta, Georgia and included leaders from the fields of neurology, neurosurgery, and psychiatry along with colleagues from industry, government, ethics, and law. The goal was to review the current state of the field, assess for advances or setbacks in the interim six years, and suggest a future path forward. The participants focused on five areas of interest: interdisciplinary engagement, regulatory pathways and trial design, disease biomarkers, ethics of psychiatric surgery, and resource allocation/prioritization. The proceedings are summarized here. CONCLUSION: The field of surgical psychiatry has made significant progress since our last expert meeting. Although weakness and threats to the development of novel surgical therapies exist, the identified strengths and opportunities promise to move the field through methodically rigorous and biologically-based approaches. The experts agree that ethics, law, patient engagement, and multidisciplinary teams will be critical to any potential growth in this area.

Proceedings of the 10th annual deep brain stimulation think tank: Advances in cutting edge technologies, artificial intelligence, neuromodulation, neuroethics, interventional psychiatry, and women in neuromodulation.

The deep brain stimulation (DBS) Think Tank X was held on August 17-19, 2022 in Orlando FL. The session organizers and moderators were all women with the theme women in neuromodulation. Dr. Helen Mayberg from Mt. Sinai, NY was the keynote speaker. She discussed milestones and her experiences in developing depression DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging DBS technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank X speakers was that DBS has continued to expand in scope however several indications have reached the "trough of disillusionment." DBS for depression was considered as "re-emerging" and approaching a slope of enlightenment. DBS for depression will soon re-enter clinical trials. The group estimated that globally more than 244,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: neuromodulation in Europe, Asia, and Australia; cutting-edge technologies, closed loop DBS, DBS tele-health, neuroethics, lesion therapy, interventional psychiatry, and adaptive DBS.

Does Personality Change Follow Deep Brain Stimulation in Parkinson's Disease Patients?

Deep Brain Stimulation (DBS) has emerged as a safe, effective, and appealing treatment for Parkinson's Disease (PD), particularly for improving motor symptoms (e. g., tremor, bradykinesia, and rigidity). However, concerns have been raised about whether DBS causes psychological changes, including changes to personality: characteristic and relatively stable patterns of affect, behavior, cognition, and desire. In this article, after first presenting some background information about PD and DBS, we examined evidence obtained from various empirical research methods (quantitative, qualitative, and mixed methods for evaluating patient valued characteristics) pertaining to whether DBS causes personality change. General limitations across research methods include a lack of randomized clinical trials and small sample sizes. We organized our review of findings according to different layers of personality variables: dispositional traits (including personality pathology), characteristic adaptations, and narrative identity. Though most work has been done on dispositional traits, there is not much evidence that dispositional traits change following DBS. Little work has been done on characteristic adaptations, but there is somewhat consistent evidence for positive perceived progress toward goals across a number of domains: routine activities, work, social/relational, and leisure. Nascent work on narrative identity holds promise for revealing issues around self-image that may be common following DBS. We listed a number of strategies for advancing research, highlighting opportunities related to personality conceptualization, personality assessment, and interdisciplinary scholarship. Finally, we offer practical applications of our findings for the informed consent process and for ongoing treatment.

Changes in Patients' Desired Control of Their Deep Brain Stimulation and Subjective Global Control Over the Course of Deep Brain Stimulation.

Objective: To examine changes in patients' desired control of the deep brain stimulator (DBS) and perception of global life control throughout DBS. Methods: A consecutive cohort of 52 patients with Parkinson's disease (PD) was recruited to participate in a prospective longitudinal study over three assessment points (pre-surgery, post-surgery months 3 and 6). Semi-structured interviews assessing participants' desire for stimulation control and perception of global control were conducted at all three points. Qualitative data were coded using content analysis. Visual analog scales were embedded in the interviews to quantify participants' perceptions of control over time. Results: Participants reported significant increases in their perception of global control over time and significant declines in their desired control of the stimulation. These changes were unrelated to improvements in motor symptoms. Improvements in global control were negatively correlated with a decline in desired stimulation control. Qualitative data indicate that participants have changed, nuanced levels of desired control over their stimulators. Increased global life control following DBS may be attributed to increased control over PD symptoms, increased ability to engage in valued activities, and increased overall self-regulation, while other domains related to global control remained unaffected by DBS. Conclusions: There are few empirical data documenting patients' desire for stimulation control throughout neuromodulation and how stimulation control is related to other aspects of control despite the growing application of neuromodulation devices to treat a variety of disorders. Our data highlight distinctions in different types of control and have implications for the development of patient-controlled neurostimulation devices.

Double blind randomized controlled trial of deep brain stimulation for obsessive-compulsive disorder: Clinical trial design.

Obsessive-compulsive disorder (OCD), a leading cause of disability, affects ~1-2% of the population, and can be distressing and disabling. About 1/3 of individuals demonstrate poor responsiveness to conventional treatments. A small proportion of these individuals may be deep brain stimulation (DBS) candidates. Candidacy is assessed through a multidisciplinary process including assessment of illness severity, chronicity, and functional impact. Optimization failure, despite multiple treatments, is critical during screening. Few patients nationwide are eligible for OCD DBS and thus a multi-center approach was necessary to obtain adequate sample size. The study was conducted over a six-year period and was a NIH-funded, eight-center sham-controlled trial of DBS targeting the ventral capsule/ventral striatum (VC/VS) region. There were 269 individuals who initially contacted the sites, in order to achieve 27 participants enrolled. Study enrollment required extensive review for eligibility, which was overseen by an independent advisory board. Disabling OCD had to be persistent for ≥5 years despite exhaustive medication and behavioral treatment. The final cohort was derived from a detailed consent process that included consent monitoring. Mean illness duration was 27.2 years. OCD symptom subtypes and psychiatric comorbidities varied, but all had severe disability with impaired quality of life and functioning. Participants were randomized to receive sham or active DBS for three months. Following this period, all participants received active DBS. Treatment assignment was masked to participants and raters and assessments were blinded. The final sample was consistent in demographic characteristics and clinical features when compared to other contemporary published prospective studies of OCD DBS. We report the clinical trial design, methods, and general demographics of this OCD DBS sample.

Clinical utility of the Boston Naming Test in predicting ultimate side of surgery in patients with medically intractable temporal lobe epilepsy: A double cross-validation study.

The Boston Naming Test (BNT) is often used in the evaluation of surgical epilepsy patients to assess left temporal lobe function. In 2005, Busch et al. demonstrated the diagnostic utility of the BNT in predicting ultimate side of surgery in patients with temporal lobe epilepsy. BNT raw score significantly predicted ultimate side of surgery, moderated by Full Scale IQ (FSIQ), age at seizure onset, and duration of epilepsy. The final regression equation correctly predicted side of surgery in 69.5% of the sample. The current study demonstrated excellent cross-validation of this equation in an independent sample of 104 patients who eventually underwent temporal lobectomies, correctly predicting side of surgery in 67.3% of patients. The combination of the two samples resulted in a new, more-stable regression equation that correctly predicted side of surgery in 68.8% of the combined sample. These results further support the clinical utility of the BNT in predicting side of surgery.

Iowa Gambling Task Performance in Parkinson Disease Patients with Impulse Control Disorders.

OBJECTIVE: A subgroup of patients with Parkinson disease (PD) develops impulse control disorders (ICD) associated with their dopamine replacement therapy. Patients and their families may be reluctant to report ICD symptoms or unaware these symptoms are related to PD medication, which can make detecting an ICD difficult for clinicians. Ideally, a behavioral measure that is sensitive to ICD could be employed to ensure that patients with these behaviors are identified and treated. The Iowa Gambling Task (IGT), a standardized decision-making task, has proven sensitive in other populations with impulse control problems. We hypothesized that the IGT would differentiate between PD patients with and without ICD. METHODS: We compared IGT performance and disease variables in 24 PD patients with ICD and 24 PD patients without ICD. Patient groups were matched in terms of age, sex, and duration of PD. RESULTS: There were no significant differences in IGT scores between PD groups. IGT performance declined with increasing age, but the majority of patients performed within normal limits based on published age- and education-corrected normative data. CONCLUSIONS: The IGT did not distinguish between PD patients with and without ICD. Increasing age negatively impacted performance in both groups. Other studies have found that IGT performance may decline in normal aging. Our results suggest that the IGT lacks the sensitivity and specificity needed to differentiate between age-related deficits and disruption in frontal-subcortical circuits underlying ICD associated with PD medications. Therefore, the IGT is not an appropriate behavioral measure for ICD in PD patients.

Pragmatism and the Importance of Interdisciplinary Teams in Investigating Personality Changes following DBS.

Gilbert and colleagues (2018) point out the discrepancy between the limited empirical data illustrating changes in personality (and related concepts of identity, agency, authenticity, autonomy, and self, i.e., PIAAAS) following implantation of deep brain stimulating (DBS) electrodes and the vast number of conceptual neuroethics papers implying that these changes are widespread, deleterious, and clinically significant. Their findings are reminiscent of C. P. Snow's essay on the divide between the two cultures of the humanities (representing the conceptual publications) and the sciences (representing the empirical work). This division in the literature raises significant ethical concerns surrounding unjustified fear of personality changes in the context of DBS and negative perceptions of clinician-scientists engaged in DBS. These concerns have real world implications for funding future innovative, DBS trials aimed to reduce suffering as well as hampering true interdisciplinary scholarship. We argue that the philosophical tradition of pragmatism and the value it places on empirical inquiry, experiential knowledge, and inter-disciplinary scholarship - reflecting diverse ways of knowing - provides a framework to start to address the important questions Gilbert and colleagues raise. In particular, we highlight the importance of expert clinician knowledge in contributing to the neuroethical questions raised by Gilbert and colleagues. Finally, we provide illustrative examples of some of our interdisciplinary empirical research that demonstrate the iterative cycle of inquiry characteristic of pragmatism in which conceptual neuroethics questions have led to empirical studies whose results then raise additional conceptual questions that give rise to new empirical studies in a way that highlights the contributions of the humanities and the sciences.

Validation of computerized episodic memory measures in a diverse clinical sample referred for neuropsychological assessment.

OBJECTIVE: To examine the convergent and discriminant validity of two brief computerized episodic memory measures in a large, diverse clinical sample of adults undergoing neuropsychological assessment. METHOD: Computerized measures of word and face memory were administered to 233 adults (age 30 and over) who also completed comprehensive neuropsychological testing. RESULTS: Moderate correlations were observed between the computerized memory tests and a wide range of traditional neuropsychological measures of episodic memory (e.g. word-list learning, story recall, face recognition, design recall). Select measures of visuomotor processing speed and language were also related to performance on the computerized tasks. In contrast, the computerized memory tests showed weak correlations with tests in other cognitive domains (i.e. visuospatial skills, attention/working memory, executive function, motor dexterity, academic skills) and self-report screening measures of mood and anxiety. Similar to traditional measures of episodic memory, the computerized memory measures were sensitive to effects of age and gender. CONCLUSIONS: Computerized measures of word and face memory showed good convergent and discriminant validity in this diverse clinical sample supporting the construct validity of these measures. This indicates that it may be feasible to measure memory function in clinical settings using brief, well-designed computerized memory measures.

Exploratory and confirmatory factor analysis of the autism diagnostic interview-revised.

The factor structure of the Autism Diagnostic Interview-Revised (ADI-R) algorithm items was examined using exploratory (EFA) and confirmatory factor analyses (CFA) factor methods. The ADI-R was completed for 1,170 youths and adults (ages 2-46). Results of EFAs indicated strong support for two-factor structure, with social communication and stereotyped behavior factors. CFAs computed in a holdout sub-sample indicated roughly equal support for the above described two-factor model and a three factor model separating peer relationships and play from other social and communicative behaviors. Multi-group CFAs suggested that both two and three factor models showed good stability across age, with only slight changes in factor relationships. These findings indicate that the current ADI-R structure be revised to more accurately reflect the relationships between sub-scales.

Who does she think she is? Women, leadership and the 'B'(ias) word.

OBJECTIVE: Despite the increasing number of women in professional fields, women are under-represented in leadership roles. The goal of this paper is to identify potential explanations for the gender gap in leadership. METHOD: The academic literature with respect to gender roles, leadership, and organizational expectations; gender differences in leadership; and the potential role of second generation bias was reviewed. RESULTS: Women are as effective as male leaders in a variety of organizational settings. The role congruity theory suggests that women are placed in a double bind: maintenance of their gender role may result in a failure to meet the requirements of a leader role whereas conforming to a leader role may result in the failure to conform to their gender role. Second generation, or implicit, bias also influences women's leadership opportunities. This is further complicated by expectations that women will engage in more altruistic organizational citizenship behaviors or be penalized. CONCLUSION: Differences in ability do not account for the gender gap in leadership. Cultural factors, including gender role and leadership expectations, organizational demands, and second-generation bias impact women's ability to lead. Pragmatic recommendations to increase women's influence and representation in leadership are provided.

The Role of a Neuropsychologist on a Movement Disorders Deep Brain Stimulation Team.

The term movement disorders is misleading in the implication that the symptoms are limited to motor problems. Most movement disorders include a variety of neurobehavioral and neurocognitive symptoms that require neuropsychological expertise. The goal of this paper is to provide a rationale and practical roadmap for neuropsychologists' involvement in a Movement Disorders team with a specific focus on pre-operative deep brain stimulation (DBS) evaluations. Pragmatic recommendations regarding requisite skills, clinical practice, recommendations, communication, and benefits are outlined.

Patients' shifting goals for deep brain stimulation and informed consent.

OBJECTIVE: To determine using a repeated-measures, prospective design whether deep brain stimulation (DBS) results in changes in the importance of symptom and behavioral goals individually identified by patients with Parkinson disease (PD) before DBS surgery. METHODS: Fifty-two participants recruited from a consecutive series completed a semistructured interview soliciting their rank-ordered symptom and behavioral goals and corresponding visual analog scales measuring perceived symptom severity and limits to goal attainment. Rank orders were reassessed at 2 times after DBS. Changes in rank order over time were examined with χ2 analyses. The relationships between change in symptom severity/limits to behavioral goal attainment and change in rank order were examined with mixed-effects linear regression models. RESULTS: Most participants changed the rank order of their symptom (81%) and behavioral (77%) goals 3 months after DBS surgery. Change in rank order of symptom goals was significantly related to change in severity ratings such that improvements in self-reported symptom severity were associated with reductions in rank. In contrast, no such relationship was evident for the behavioral goals. CONCLUSION: These data illustrate how patients' primary goals for DBS shift early in stimulation and highlight the important differences between symptom and behavioral goals. Changes in the rank order of symptom goals were related to changes in symptom severity, whereas subtler shifts in behavioral goals were unrelated to improvements after DBS. This observation suggests that DBS does not affect goals that may be more reflective of core personal values. The findings provide empiric data that can help improve the informed consent process.

Clinical Ethics in the Context of Deep Brain Stimulation for Movement Disorders.

OBJECTIVE: Discuss common clinical ethical challenges encountered in working with patients who are candidates for deep brain stimulation (DBS) for the treatment of motor symptoms of Parkinson's disease (PD). METHOD: The relevant literature is reviewed and supplemented by descriptive, ethically challenging cases stemming from decades of combined experience working on DBS teams. We outline ethical arguments and provide pragmatic recommendations to assist neuropsychologists working in movement disorder teams. RESULTS: The goals of the pre-operative neuropsychological DBS assessment include: (1) identification of potential cognitive risk factors; (2) identification of relevant neuropsychiatric or neurobehavioral factors; (3) assessment of level of family support; and (4) systematic assessment of patient's and family member's goals or expectations for DBS. The information gleaned from the pre-operative neuropsychological assessment is highly relevant to the most commonly studied clinical ethics challenges encountered in DBS: (1) assessment of risk/benefit; (2) determinations regarding inclusion/exclusion; (3) autonomy; and (4) patient's perception of benefit and quality of life. CONCLUSIONS: Neuropsychologists are particularly well poised to provide unique and important insights to assist with developing the most ethically sound practices that take into account patient's values as well as fiduciary responsibilities to the patient, the team, the profession, and the broader community.