Loss of Efficacy in Ventral Intermediate Nucleus Stimulation for Essential Tremor.

OBJECTIVE: The primary aim of this study is to report long-term outcomes associated with deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) performed at our institution. We further aimed to elicit the factors associated with loss of efficacy and to discuss the need for exploring and establishing reliable rescue targets. METHODS: To study long-term outcomes, we performed a retrospective chart review and extracted tremor scores of 43 patients who underwent VIM DBS lead implantation for essential tremor at our center. We further evaluated factors that could influence outcomes over time, including demographics, body mass index, duration of follow-up, degree of parenchymal atrophy indexed by the global cortical atrophy scale, and third ventricular width. RESULTS: In this cohort, tremor scores on the latest follow-up (median 52.7 months) were noted to be worse than initial postoperative scores in 56% of DBS leads. Furthermore, 14% of leads were associated with clinically significant loss of benefit. Factors including the length of time since the lead implantation, age at the time of surgery, sex, body mass index, preoperative atrophy, and third ventricular width were not predictive of long-term outcomes. CONCLUSIONS: Our study identified a substantial subgroup of VIM-DBS patient who experienced a gradual decline in treatment efficacy over time. We propose that this phenomenon can be attributed primarily to habituation and disease progression. Furthermore, we discuss the need to establish reliable and effective rescue targets for this subpopulation of patients, with ventral-oralis complex and dentate nucleus emerging as potential candidates.

Utility of the Brief Assessment of Cognitive Health (BACH) computerized screening tool in identifying MS-related cognitive impairment.

BACKGROUND: Current guidelines recommend that individuals with MS are screened annually for processing speed deficits, often using the Symbol Digit Modalities Test (SDMT). However, given the heterogeneity of cognitive deficits in individuals with MS, other screening measures that assess a range of cognitive domains are necessary. The current cross-sectional study aimed to examine the ability of the computerized, self-administered Brief Assessment of Cognitive Health (BACH) screening measure to detect the presence of cognitive impairment in adults with MS as determined by performance on a standard neuropsychological test battery. METHODS: Seventy-two individuals with MS completed the BACH and a comprehensive neuropsychological test battery. Receiver operating characteristic (ROC) analyses were conducted to investigate the ability of the BACH to identify cognitively impaired and cognitively intact individuals. ROC analyses were also conducted to compare the ability of the SDMT to discriminate between cognitively intact and cognitively impaired groups as a comparison with the BACH. RESULTS: Cognitive impairment was observed in 56 % of the sample. The BACH showed acceptable ability to discriminate between cognitively intact and cognitively impaired groups (AUC = 0.78). Additionally, the BACH was able to adequately predict cognitive impairment in domains other than processing speed (AUC = 0.71). The SDMT also demonstrated adequate utility in identifying individuals with cognitive impairment (AUC = 0.73); however, the SDMT was not able to adequately predict cognitive impairment in domains other than processing speed (AUC = 0.56). CONCLUSION: The BACH showed adequate ability to detect cognitive impairment in individuals with MS. The BACH was able to identify impairments across various assessed cognitive domains, including individuals with and without processing speed deficits.

Validation of Self-Administered Visual and Verbal Episodic Memory Tasks in Healthy Controls and a Clinical Sample.

This study evaluated the performance characteristics, construct validity, and reliability of two computerized, self-administered verbal and visual recognition memory tests based on the Remember-Know paradigm. Around 250 healthy control participants and 440 patients referred for neuropsychological assessment used an iPad to complete the Words and Faces recognition memory tests before or after concurrent neuropsychological testing. Performance accuracy was high but without ceiling effects. Education, but not age, was related to overall performance for both samples while the influence of gender and race differed across samples. In the clinical sample, overall performance was worse in those patients demonstrating memory impairment on clinical assessment. Words and Faces subtests demonstrated the strongest correlations with neuropsychological measures of verbal and nonverbal memory, respectively. Both showed moderate correlations with processing speed while Faces was also correlated with visuospatial skills. The memory tests showed good test-retest reliability over two testing sessions. These findings demonstrate acceptable psychometric properties in clinical and community samples and suggest that this computerized format is feasible for memory assessment in clinical contexts.

Cerebellar deep brain stimulation for chronic post-stroke motor rehabilitation: a phase I trial.

Upper-extremity impairment after stroke remains a major therapeutic challenge and a target of neuromodulation treatment efforts. In this open-label, non-randomized phase I trial, we applied deep brain stimulation to the cerebellar dentate nucleus combined with renewed physical rehabilitation to promote functional reorganization of ipsilesional cortex in 12 individuals with persistent (1-3 years), moderate-to-severe upper-extremity impairment. No serious perioperative or stimulation-related adverse events were encountered, with participants demonstrating a seven-point median improvement on the Upper-Extremity Fugl-Meyer Assessment. All individuals who enrolled with partial preservation of distal motor function exceeded minimal clinically important difference regardless of time since stroke, with a median improvement of 15 Upper-Extremity Fugl-Meyer Assessment points. These robust functional gains were directly correlated with cortical reorganization evidenced by increased ipsilesional metabolism. Our findings support the safety and feasibility of deep brain stimulation to the cerebellar dentate nucleus as a promising tool for modulation of late-stage neuroplasticity for functional recovery and the need for larger clinical trials. ClinicalTrials.gov registration: NCT02835443 .

Deep cerebellar stimulation enhances cognitive recovery after prefrontal traumatic brain injury in rodent.

Functional outcome following traumatic brain injury (TBI) varies greatly, with approximately half of those who survive suffering long-term motor and cognitive deficits despite contemporary rehabilitation efforts. We have previously shown that deep brain stimulation (DBS) of the lateral cerebellar nucleus (LCN) enhances rehabilitation of motor deficits that result from brain injury. The objective of the present study was to evaluate the efficacy of LCN DBS on recovery from rodent TBI that uniquely models the injury location, chronicity and resultant cognitive symptoms observed in most human TBI patients. We used controlled cortical impact (CCI) to produce an injury that targeted the medial prefrontal cortex (mPFC-CCI) bilaterally, resulting in cognitive deficits. Unilateral LCN DBS electrode implantation was performed 6 weeks post-injury. Electrical stimulation started at week eight post-injury and continued for an additional 4 weeks. Cognition was evaluated using baited Y-maze, novel object recognition task and Barnes maze. Post-mortem analyses, including Western Blot and immunohistochemistry, were conducted to elucidate the cellular and molecular mechanisms of recovery. We found that mPFC-CCI produced significant cognitive deficits compared to pre-injury and naïve animals. Moreover, LCN DBS treatment significantly enhanced the long-term memory process and executive functions of applying strategy. Analyses of post-mortem tissues showed significantly greater expression of CaMKIIα, BDNF and p75NTR across perilesional cortex and higher expression of postsynaptic formations in LCN DBS-treated animals compared to untreated. Overall, these data suggest that LCN DBS is an effective treatment of cognitive deficits that result from TBI, possibly by activation of ascending, glutamatergic projections to thalamus and subsequent upregulation of thalamocortical activity that engages neuroplastic mechanisms for facilitation of functional re-organization. These results support a role for cerebellar output neuromodulation as a novel therapeutic approach to enhance rehabilitation for patients with chronic, post-TBI cognitive deficits that are unresponsive to traditional rehabilitative efforts.

Neuropsychological outcomes after thalamic deep brain stimulation for essential tremor.

INTRODUCTION: Non-motor DBS outcomes have received little attention in ET relative to PD. This study examines neuropsychological outcomes in ET following thalamic VIM DBS. METHODS: Fifty patients completed neuropsychological evaluations preoperatively and approximately seven months postoperatively. Cognition and mood changes were analyzed at the group level and individual level. Additional associations with treatment, disease, and demographic characteristics were assessed. RESULTS: Significant cognitive decline was not observed at the group level. At the individual level, 46% of patients demonstrated at least subtle overall cognitive decline (≥1SD on at least one test within at least two domains). Mild decline (≥1SD) was seen in 10%-29.17% of patients on individual tests across all cognitive domains, with highest rates in verbal memory. Substantial cognitive decline (≥2SD) occurred in less than 9% of the sample across all tests. Factors related to cognitive decline included higher DBS parameter settings, older age of ET onset, intracranial complications, and inability to reduce ET medications postoperatively. Depression and anxiety did not change when accounting for questionnaire items that could be falsely elevated by tremor. CONCLUSION: Substantial cognitive decline after VIM DBS is rare in patients with ET. However, subtle decrements can occur across cognitive domains and particularly in verbal memory. DBS parameter settings may relate to cognitive decline. Further research is needed to better understand possible associations with electrode lateralization and other variables that could also relate to disease progression and test-retest effects. Symptoms of depression and anxiety remain stable.

Long-Term Neurocognitive Outcome in Patients With Continuous Flow Left Ventricular Assist Device.

OBJECTIVES: The authors sought to examine the long-term cognitive outcome of patients with continuous flow left ventricular assist device (CF-LVAD). BACKGROUND: Data on long-term neurocognitive outcome in LVAD are limited. We examined the neurocognitive outcome of patients who received a CF-LVAD as destination therapy. METHODS: Patients with HeartWare (HVAD) and HeartMate II who were enrolled in the ENDURANCE and ENDURANCE Supplemental trials were eligible. Cognition was evaluated with neuropsychological testing preoperatively and at 6, 12, and 24 months after implantation. General linear models identified demographic, disease, and treatment factors that predicted decline on each neurocognitive measure. RESULTS: Of 668 patients who completed baseline testing and at least 1 follow-up evaluation, 552 were impaired at baseline on at least 1 cognitive measure. At each follow-up, approximately 23% of tested patients declined and 20% improved relative to baseline on at least 1 cognitive measure. Of those who were intact at baseline, only 10%-12% declined in delayed memory and 11%-16% declined in executive function at all 3 follow-ups. For patients impaired at baseline, delayed memory decline was associated with the HVAD device and male sex, whereas executive function decline was associated with the HVAD device and stroke during CF-LVAD support. For patients intact at baseline, male sex and history of hypertension were associated with decline in immediate memory and executive function, respectively. CONCLUSIONS: Neurocognitive function remained stable or improved for most patients (∼80%) with CF-LVAD at 6, 12, and 24 months after implantation. Male sex, hypertension, HVAD, and stroke were associated with cognitive decline.

Cognitive outcomes following frontal lobe resection for treatment of epilepsy in children and adolescents.

OBJECTIVE: To use reliable change indices (RCIs) developed specifically for pediatric patients with epilepsy to examine cognitive outcomes after frontal lobe resection for pharmacoresistant epilepsy. METHODS: Forty-one pediatric patients (25 male, Mage = 10 years) completed comprehensive neuropsychological evaluations before and an average of 6.5 months after frontal lobe resections for treatment of epilepsy. Evaluations included tests of intelligence, attention/working memory, processing speed, language, visuospatial skills, executive function, and episodic memory. Practice effect-adjusted RCIs were used to determine clinically significant postoperative cognitive change. Demographic, disease, and surgical variables were examined to identify factors associated with postoperative cognitive decline or improvement. RESULTS: Within each cognitive domain, there was a large proportion of patients (51-84%) who did not exhibit significant cognitive change. In terms of overall cognitive profile, 44% demonstrated improvement in at least one domain and 69% declined in at least one domain. Postoperative cognitive improvement occurred most commonly in the domain of processing speed, whereas postoperative cognitive decline occurred most frequently in the domain of visuospatial skills. Younger age at surgery was associated with cognitive improvement. Older age at seizure onset and higher baseline cognitive performance were associated with cognitive decline. SIGNIFICANCE: Approximately 6.5 months after frontal lobe resection, only 15% of our sample showed stable performance across all cognitive domains. Seventeen percent of patients showed improvements without declines, 42% showed declines without improvements, and 27% showed a mix of improvements and declines across different cognitive domains. Age and baseline abilities were associated with postoperative cognitive change on multiple measures. With 1 in 8 children demonstrating postoperative decline across three or more domains, further research is needed to identify factors associated with cognitive decline in order to inform clinical decision-making and patient/family counseling.

Cortical thickness in visuo-motor areas is related to motor outcomes after STN DBS for Parkinson's disease.

INTRODUCTION: Deep brain stimulation (DBS) is a widely accepted therapy for Parkinson's disease. While outcome predictors such as levodopa-response are well established, there remains a need for objective and unbiased predictors in clinical practice. We performed an exploratory study to examine whether cortical thickness, derived from preoperative MRI, correlates with postoperative outcome. METHODS: Using freesurfer, we retrospectively measured cortical thickness on the preoperative MRI of 38 patients who underwent bilateral STN-DBS for PD during a 4-year period. The Unified Parkinson Disease Rating motor (UPDRS III) and experiences of daily living subscales (UPDRS II) were collected at baseline and six months after surgery. As an initial analysis, a series of partial correlations was conducted to evaluate the association between postoperative outcome scores and average cortical thickness from predefined regions of interest, adjusting for candidate confounders, without correcting for multiple comparisons. A confirmatory vertex-wise analysis was performed using a cluster-wise correction for multiple comparisons. RESULTS: Based on the ROI analysis, the strongest correlation with motor outcome was found to be with the left lateral-occipital cortex. Patients with greater cortical thickness in this area presented with greater improvements in motor scores. This relationship was also supported by the vertex-wise analysis. Greater cortical thickness in frontal and temporal regions may be correlated with greater post-operative improvements in UPDRS II, but this was not confirmed in the vertex-wise analysis. CONCLUSIONS: Our data indicate that greater cortical thickness in visuo-motor areas is correlated with motor outcomes after DBS for PD. Further prospective investigations are needed to confirm our findings and better-investigate potential image biomarkers.

Factors Associated With Postoperative Confusion and Prolonged Hospital Stay Following Deep Brain Stimulation Surgery for Parkinson Disease.

BACKGROUND: Several patient and disease characteristics are thought to influence DBS outcomes; however, most previous studies have focused on long-term outcomes with only a few addressing immediate postoperative course. OBJECTIVE: To evaluate predictors of immediate outcomes (postoperative confusion and length of postoperative hospitalization) following deep brain stimulation surgery (DBS) in Parkinson disease (PD) patients. METHODS: We conducted a retrospective study of PD patients who underwent DBS at our institution from 2006 to 2011. We computed the proportion of patients with postoperative confusion and those with postoperative hospitalization longer than 2 d. To look for associations, Fisher's exact tests were used for categorical predictors and logistic regression for continuous predictors. RESULTS: We identified 130 patients [71% male, mean age: 63 ± 9.1, mean PD duration: 10.7 ± 5.1]. There were 7 cases of postoperative confusion and 19 of prolonged postoperative hospitalization. Of the 48 patients with tremors, none had postoperative confusion, whereas 10.1% of patients without tremors had confusion (P = .0425). Also, 10.2% of patients with preoperative falls/balance-dysfunction had postoperative confusion, whereas only 1.6% of patients without falls/balance-dysfunction had postoperative confusion (P = .0575). For every one-unit increase in score on the preoperative on-UPDRS III/MDS-UPDRS III score, the odds of having postoperative confusion increased by 10% (P = .0420). The following factors were noninfluential: age, disease duration, dyskinesia, gait freezing, preoperative levodopa-equivalent dose, number of intraoperative microelectrode passes, and laterality/side of surgery. CONCLUSION: Absence of tremors and higher preoperative UPDRS III predicted postoperative confusion after DBS in PD patients. Clinicians' awareness of these predictors can guide their decision making regarding patient selection and surgical planning.

BDNF and COMT, but not APOE, alleles are associated with psychiatric symptoms in refractory epilepsy.

OBJECTIVE: The objective of this study was to determine whether three common genetic polymorphisms [apolipoprotein (APOE) ε4 (rs42938 and rs7412), brain derived neurotrophic factor (BDNF) Met (rs6265), and catechol-O-methyltransferase (COMT) Val (rs4680)] are associated with increased psychiatric symptomatology in individuals with pharmacoresistant epilepsy. METHODS: One hundred forty-eight adults (Mage = 38 years; 53% female) with refractory epilepsy completed self-report measures of mood, anxiety, and/or personality/psychopathology. Mann-Whitney U, t-tests, and Fisher's exact tests were used to determine if APOE4, BDNF Val66Met, or COMT Val158Met are associated with increased psychiatric symptomatology in people with epilepsy. RESULTS: As a group, BDNF Met carriers reported greater symptoms of depression on the Personality Assessment Inventory (PAI) than those without a Met allele (p = 0.004); COMT Val carriers reported greater symptoms on the PAI Schizophrenia (p = 0.007), Antisocial Features (p = 0.04), and Alcohol Problems (p = 0.03) scales than noncarriers. On the individual level, a significantly greater proportion of BDNF Met carriers demonstrated elevated PAI Depression scores compared to those without a Met allele (p = 0.046). There was also a larger proportion of COMT Val carriers with elevated PAI Anxiety scores as compared to those without a Val allele (p = 0.036). SIGNIFICANCE: This retrospective cross-sectional study provides preliminary evidence for a genetic basis of psychiatric comorbidities in epilepsy and suggests that BDNF and COMT may play an important role in the pathophysiology of mental health problems in this vulnerable population.

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.

Quality of Life Improvement Following Deep Brain Stimulation for Parkinson Disease: Development of a Prognostic Model.

BACKGROUND: There is a growing attention to determine the factors that predict quality of life (QoL) improvement after deep brain stimulation (DBS) for Parkinson's disease. Prior literature has largely focused on examining predictors one at a time, sometimes controlling for covariates. OBJECTIVE: To develop a model that could be used as a nomogram to predict improvement in QoL following DBS surgery in patients with Parkinson's disease. METHODS: All patients with complete pre- and postoperative movement disorder and neuropsychological testing who underwent DBS at a single institution between 2007-2012 were analyzed. The Parkinson's Disease Questionnaire-39 (PDQ-39) was used to measure QoL. Potential predictive factors, including patient demographics, clinical presentation characteristics, radiographic imaging, and motor and psychological testing were analyzed for impact on QoL. RESULTS: Sixty-seven patients were identified, 36 (53.73%) of whom had meaningfully improved QoL following surgery. Five baseline variables showed significant relationships with the outcome: years since symptom onset, percent change in on/off motor evaluation, levodopa equivalent daily dose, bilateral vs unilateral DBS implantation, and PDQ-39 score. The final model includes PDQ-39, percent change in UPRS-III, and years since symptom onset and is able to predict improvement in QoL with 81% accuracy. CONCLUSION: Our model accurately predicted whether QoL would improve in patients undergoing subthalamic nucleus DBS 81% of the time. Our data may serve as the foundation to further refine a clinically relevant prognostic tool that would assist the decision-making process for clinicians and DBS multidisciplinary teams assessing patient candidacy for surgery.

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.

Lack of Accurate Self-appraisal is Equally Likely in MCI from Parkinson's Disease and Alzheimer's Disease.

BACKGROUND: How accurate are mild cognitive impairment (MCI) patients in assessing their cognitive and functional deficit is often unclear to the clinician. The accuracy of patient self-appraisal in Parkinson's disease-MCI (PD-MCI) has received less attention than amnestic MCI (a-MCI) often associated with Alzheimer's disease. We evaluated if PD-MCI patients demonstrate accurate self-appraisal of their cognitive deficits compared to patients with amnestic a-MCI or non-amnestic MCI (na-MCI). METHODS: This cross-sectional cohort study included, 30 PD-MCI, 33 a-MCI, and 17 na-MCI patients. Self-appraisal was assessed by comparing responses of caregivers and patients on a validated self-rating questionnaire of cognitive and functional impairments. All patients completed a full neuropsychological evaluation and depression screening measure. Univariate ANOVA, regression, and correlational analyses were employed to identify group differences in self-appraisal scores and relationships between cognitive and functional impairment, depression measures, and self-appraisal scores. RESULTS: Self-appraisal scores for PD-MCI did not differ significantly from a-MCI and na-MCI. In the PD-MCI group, higher depression scores were associated with lower self-appraisal scores (i.e, patients assessed cognition as worse than caregivers). In a stepwise regression model with self-appraisal scores as the dependent variable, only the depression score was significant predictor among PD-MCI and accounted for 50% of the variance. CONCLUSIONS: Our findings suggest that impaired patient self-appraisal is equally likely to occur in PD-MCI as in a-MCI and na-MCI patients. Among PD-MCI, depression was the strongest predictor of impaired patient self-appraisal. Impaired insight into cognitive impairment and depression should be considered in both care and research with PD patients.

Predicting early cognitive decline in newly-diagnosed Parkinson's patients: A practical model.

OBJECTIVE: To create a multivariable model to predict early cognitive decline among de novo patients with Parkinson's disease, using brief, inexpensive assessments that are easily incorporated into clinical flow. METHODS: Data for 351 drug-naïve patients diagnosed with idiopathic Parkinson's disease were obtained from the Parkinson's Progression Markers Initiative. Baseline demographic, disease history, motor, and non-motor features were considered as candidate predictors. Best subsets selection was used to determine the multivariable baseline symptom profile that most accurately predicted individual cognitive decline within three years. RESULTS: Eleven per cent of the sample experienced cognitive decline. The final logistic regression model predicting decline included five baseline variables: verbal memory retention, right-sided bradykinesia, years of education, subjective report of cognitive impairment, and REM behavior disorder. Model discrimination was good (optimism-adjusted concordance index = .749). The associated nomogram provides a tool to determine individual patient risk of meaningful cognitive change in the early stages of the disease. CONCLUSIONS: Through the consideration of easily-implemented or routinely-gathered assessments, we have identified a multidimensional baseline profile and created a convenient, inexpensive tool to predict cognitive decline in the earliest stages of Parkinson's disease. The use of this tool would generate prediction at the individual level, allowing clinicians to tailor medical management for each patient and identify at-risk patients for clinical trials aimed at disease modifying therapies.

Deep brain stimulation of the ventral striatal area for poststroke pain syndrome: a magnetoencephalography study.

Poststroke pain syndrome (PSPS) is an often intractable disorder characterized by hemiparesis associated with unrelenting chronic pain. Although traditional analgesics have largely failed, integrative approaches targeting affective-cognitive spheres have started to show promise. Recently, we demonstrated that deep brain stimulation (DBS) of the ventral striatal area significantly improved the affective sphere of pain in patients with PSPS. In the present study, we examined whether electrophysiological correlates of pain anticipation were modulated by DBS that could serve as signatures of treatment effects. We recorded event-related fields (ERFs) of pain anticipation using magnetoencephalography (MEG) in 10 patients with PSPS preoperatively and postoperatively in DBS OFF and ON states. Simple visual cues evoked anticipation as patients awaited a painful (PS) or nonpainful stimulus (NPS) to the nonaffected or affected extremity. Preoperatively, ERFs showed no difference between PS and NPS anticipation to the affected extremity, possibly due to loss of salience in a network saturated by pain experience. DBS significantly modulated the early N1, consistent with improvements in affective networks involving restoration of salience and discrimination capacity. Additionally, DBS suppressed the posterior P2 (aberrant anticipatory anxiety) while enhancing the anterior N1 (cognitive and emotional regulation) in responders. DBS-induced changes in ERFs could potentially serve as signatures for clinical outcomes. NEW & NOTEWORTHY We examined the electrophysiological correlates of pain affect in poststroke pain patients who underwent deep brain stimulation (DBS) targeting the ventral striatal area under a randomized, controlled trial. DBS significantly modulated early event-related components, particularly N1 and P2, measured with magnetoencephalography during a pain anticipatory task, compared with baseline and the DBS-OFF condition, pointing to possible mechanisms of action. DBS-induced changes in event-related fields could potentially serve as biomarkers for clinical outcomes.

Contact Location and Neuropsychological Outcomes in Subthalamic Deep Brain Stimulation.

BACKGROUND: A host of influences contribute to cognitive and behavioral changes following deep brain stimulation. The location of the active cathode is likely an important variable but it has received little attention. OBJECTIVE: To determine whether active contact location relative to the subthalamic nucleus and other neighboring structures is related to nonmotor outcomes. METHODS: We identified a retrospective, cross-sectional sample of 46 patients who underwent subthalamic nucleus deep brain stimulation for treatment of idiopathic Parkinson's disease. T-tests or nonparametric equivalents were used to detect baseline differences between unilateral left, unilateral right, and bilateral surgical groups. Correlation and partial correlational analyses identified relationships between contact location variables and alterations in cognitive, mood, quality of life, motor, and disease variables. RESULTS: Medial contact locations within the left subthalamic nucleus were correlated with improvements in self-reported mood (r12 = -0.78, P = .001; 95% confidence interval [CI] = -0.43 to -0.93) but worsening semantic fluency (r26 = -0.38, P = .048; 95% CI = -0.01 to -0.66). Phonemic fluency worsened with more posterior left placement (r34 = 0.35, P = .036; 95% CI = 0.03 to 0.61). Memory outcome was related to right hemisphere stimulation voltage (r29 = -0.40, P = .022; 95% CI = -0.05 to -0.66), which is likely a proxy for variable electrode location. CONCLUSION: Location of the active contact is related to nonmotor outcomes, even in electrodes that are adequately placed. This is relevant to clinical care as there appears to be a trade-off between mood and fluency abilities that should be considered during surgical planning according to preoperative patient characteristics.

Predictors of Functional and Quality of Life Outcomes following Deep Brain Stimulation Surgery in Parkinson's Disease Patients: Disease, Patient, and Surgical Factors.

OBJECTIVE: The primary objective was to evaluate predictors of quality of life (QOL) and functional outcomes following deep brain stimulation (DBS) in Parkinson's disease (PD) patients. The secondary objective was to identify predictors of global improvement. METHODS: PD patients who underwent DBS at our Center from 2006 to 2011 were evaluated by chart review and email/phone survey. Postoperative UPDRS II and EQ-5D were analyzed using simple linear regression adjusting for preoperative score. For global outcomes, we utilized the Patient Global Impression of Change Scale (PGIS) and the Clinician Global Impression of Change Scale (CGIS). RESULTS: There were 130 patients in the dataset. Preoperative and postoperative UPDRS II and EQ-5D were available for 45 patients, PGIS for 67 patients, and CGIS for 116 patients. Patients with falls/postural instability had 6-month functional scores and 1-year QOL scores that were significantly worse than patients without falls/postural instability. For every 1-point increase in preoperative UPDRS III and for every 1-unit increase in body mass index (BMI), the 6-month functional scores significantly worsened. Patients with tremors, without dyskinesia, and without gait-freezing were more likely to have "much" or "very much" improved CGIS. CONCLUSIONS: Presence of postural instability, high BMI, and worse baseline motor scores were the greatest predictors of poorer functional and QOL outcomes after DBS.