Change in fatigue after bilateral subthalamic nucleus deep brain stimulation for Parkinson's disease

BackgroundBilateral subthalamic nucleus (STN) deep brain stimulation (DBS) improves motor function in patients with medically intractable Parkinson’s disease (PD), but the effects of STN DBS on fatigue are unknown. The purpose of this study was to examine the effects of STN DBS on fatigue scores in patients with PD.MethodsTwenty PD patients underwent bilateral STN DBS surgery at our institution from 2007 to 2009. Only data from the 17 patients who completed the Parkinson Fatigue Scale (PFS) and Unified PD Rating Scale (UPDRS) before and approximately 6 months after surgery were analyzed. Other evaluations included the Geriatric Depression Scale (GDS), Apathy Evaluation Scale (AES), and Epworth Sleepiness Scale (ESS).ResultsWhen the cohort was analyzed as a whole, there was no significant change in the mean or binary PFS score from baseline to the 6 month evaluation. However, the fatigue response of individual subjects was variable. Six of 12 subjects with fatigue before surgery were not fatigued post-operatively, while 3/5 subjects without fatigue before surgery became fatigued after DBS surgery. Fatigue in 8 subjects remained unchanged. Change in fatigue scores correlated significantly with change in the motor UPDRS, GDS and AES. Improvement in PFS also correlated with a higher PFS baseline score and higher baseline UPDRS motor off score.ConclusionsChanges in fatigue severity were not observed in our cohort as a whole, but there were changes in fatigue on an individual level. These changes appear to be related to the effects of STN DBS on motor improvement and mood.     

Unilateral subthalamic nucleus deep brain stimulation improves sleep quality in Parkinson's disease

BackgroundSleep disturbances are common in Parkinson’s disease (PD). Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is superior to best medical therapy in the treatment of motor symptoms in advanced PD, and observational studies suggest that bilateral STN DBS improves sleep in these patients as well. Unilateral STN DBS also improves motor function in PD, but its effects on sleep have not been extensively investigated.MethodsWe report the effects of unilateral STN DBS on subjective sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI) in 53 consecutive PD patients. These subjects completed the PSQI prior to surgery and at 3 and 6 months post-operatively. The primary outcome measure was the change in the global PSQI at 6 months post-operatively versus the pre-operative baseline, measured with repeated measures analysis of variance (ANOVA).ResultsPatients with PD who underwent unilateral STN DBS had a significant improvement in PSQI at 6 months post-operatively (baseline 9.30 ± 0.56 (mean ± SEM), 6 months: 7.93 ± 0.56, p = 0.013). Supplemental analyses showed that subjects selected for STN DBS placed on the right had worse baseline subjective sleep quality and more improvement in PSQI at 6 months compared to patients who received left STN DBS.ConclusionThis prospective case series study provides evidence that unilateral STN DBS improves subjective sleep quality in patients with PD at up to 6 months post-operatively as measured by the PSQI.     

Long-term cognitive outcome of bilateral subthalamic deep brain stimulation in Parkinson’s disease

The effect of subthalamic deep brain stimulation (STN DBS) on cognition in Parkinson’s disease (PD) remains controversial, and it is unclear which factors are related to cognitive decline and dementia after STN DBS, especially over the long term. To this end, we analyzed the cognitive outcome of 103 non-demented patients with PD who were followed-up for at least 12 months after bilateral STN DBS surgery. Preoperatively, the patients were evaluated with the Unified Parkinson's Disease Rating Scale and neuropsychological tests. The rate of global cognitive decline and the incidence of dementia during follow-up for up to 7 years (mean 42.4 ± 24.5 months) were calculated, and preoperative clinical and neuropsychological factors associated with postoperative global cognitive decline or dementia were analyzed. The prevalence of mild cognitive impairment (MCI) and its relation to later cognitive decline or dementia were also evaluated. The annual decline in the mini–mental state examination score was 0.4 ± 1.7 with impaired attention and executive function and a higher levodopa equivalent dose at baseline being the predictors of a faster global cognitive decline after STN DBS. Dementia developed in 13 patients with an incidence rate of 35.7 per 1,000 person-years. Impaired executive function at baseline predicted dementia. At baseline, 63.1 % of the patients had PD-MCI, and these patients were more likely to develop dementia than those without PD-MCI. This study showed that dysfunctions in the frontostriatal circuitry at baseline were associated with a risk of subsequent global cognitive decline and dementia in patients with PD who underwent STN DBS. In addition, preoperative PD-MCI was a risk factor for dementia after STN DBS.     

Decline in drawing ability and cerebral perfusion in Parkinson's disease patients after subthalamic nucleus deep brain stimulation surgery

BackgroundSubthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for alleviating motor symptoms in advanced Parkinson's disease (PD) patients; however, a postoperative decline in cognitive and speech function has become problematic although its mechanism remains unclear. The aim of the present study was to elucidate the properties of language and drawing ability and cerebral perfusion in PD patients after bilateral STN DBS surgery.MethodsWestern aphasia battery, including drawing as a subcategory, and perfusion (N-isopropyl-p-[¹²³I] iodoamphetamine) SPECT scan was conducted in 21 consecutive PD patients, before, and three to six months after, bilateral STN DBS surgery while on stimulation. Perfusion images were compared with those of 17 age- and gender-matched healthy volunteers. In the parametric image analysis, the statistical peak threshold was set at P < 0.001 uncorrected with a cluster threshold set at P < 0.05 uncorrected.ResultsAlthough motor symptoms were improved and general cognition was preserved in the patient group, 11 patients (52.4%) showed a decline in the drawing subcategory after surgery, which showed a reduction in Frontal Assessment Battery score in this group of patients. Statistical parametric analysis of the brain perfusion images showed a decrease of cerebral blood flow in the prefrontal and cingulate cortex after surgery. Patients whose drawing ability declined showed decreased perfusion in the middle cingulate cortex comparing before and after surgery.ConclusionPresent results show that some PD patients show a decline in drawing ability after bilateral STN DBS which may attributable by dysfunction in the cingulate network.     

Temporary deterioration of executive function after subthalamic deep brain stimulation in Parkinson's disease

Objective

Selective impairment of executive function has been shown in Parkinson's Disease (PD) patients undergoing Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN). However, some patients experience difficulties in daily life, such as dissension in interpersonal relationships or a loss of lifestyle balance, in the short term after surgery. Our hypothesis is that these difficulties might be related to executive dysfunction. To elucidate the involvement of executive dysfunction in these difficulties, we assessed motor and executive function in the short term and long term after surgery.

Methods

We examined motor function and executive function in 30 patients who underwent bilateral STN–DBS for medically refractory PD. Patients were evaluated for executive function 1 month before surgery, 1 month after surgery, and 12 months after surgery using the Trail Making Test (TMT), the Modified Stroop Color Word Interference Test (MST) and tests of Verbal Fluency (VF).

Results

TMT-B, TMT (B/A), MST-B, VF-phonemic and VF-semantic scores were significantly poorer 1 month after STN–DBS. TMT-B, TMT (B/A) and VF-phonemic recovered to preoperative levels by 12 months after surgery. A reduction in dopaminergic medication 1 month after surgery was significantly correlated with deterioration of TMT (B/A).

Conclusion

Temporary deterioration of executive function may occur in the short term after STN–DBS, whereas motor function is usually improved. PD patients undergoing STN–DBS should be managed during this period to better predict temporary executive dysfunction. Excessive reduction of dopaminergic medication after surgery might, at least in part, result in this deterioration of executive function.     

Acute Changes in Mood Induced by Subthalamic Deep Brain Stimulation in Parkinson Disease Are Modulated by Psychiatric Diagnosis

BackgroundDeep brain stimulation of the subthalamic nucleus (STN DBS) reduces Parkinson disease (PD) motor symptoms but has unexplained, variable effects on mood.ObjectiveThe study tested the hypothesis that pre-existing mood and/or anxiety disorders or increased symptom severity negatively affects mood response to STN DBS.MethodsThirty-eight PD participants with bilateral STN DBS and on PD medications were interviewed with Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) and completed Beck Depression Inventory (BDI) and Spielberger State Anxiety Inventory (SSAI) self-reports. Subsequently, during OFF and optimal ON (clinical settings) STN DBS conditions and while off PD medications, motor function was assessed with the United Parkinson Disease Rating Scale (UPDRS, part III), and participants rated their mood with Visual Analogue Scales (VAS), and again completed SSAI. VAS mood variables included anxiety, apathy, valence and emotional arousal.ResultsSTN DBS improved UPDRS scores and mood. Unexpectedly, PD participants diagnosed with current anxiety or mood disorders experienced greater STN DBS-induced improvement in mood than those diagnosed with remitted disorders or who were deemed as having never met threshold criteria for diagnosis. BDI and SSAI scores did not modulate mood response to STN DBS, indicating that clinical categorical diagnosis better differentiates mood response to STN DBS than self-rated symptom severity. SCID diagnosis, BDI and SSAI scores did not modulate motor response to STN DBS.ConclusionsPD participants diagnosed with current mood or anxiety disorders are more sensitive to STN DBS-induced effects on mood, possibly indicating altered basal ganglia circuitry in this group.     

Cognitive predictors of cognitive change following bilateral subthalamic nucleus deep brain stimulation in Parkinson’s disease

The beneficial effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the motor symptoms in advanced Parkinson’s disease (PD) are well established. Early in PD, mild cognitive impairment is present in a proportion of patients. Hence, it can also be present in PD patients considered for DBS. The potential impact of even a modest decline post-surgically is a concern because it could result in impaired cognitive function. Therefore, attempts to determine which pre-operative cognitive measures predict post-operative cognitive change warrant further attention. We report our findings in a cohort of 30 routinely operated non-demented patients who underwent detailed neuropsychological assessments on average 7.1 months before and 9.4 months after STN DBS. We report the individual and group differences pre- and post-DBS. Stepwise regression analysis was used to analyse the best cognitive predictors of post-operative cognitive changes. We describe our data in relation to published normative data. Post-STN DBS, the immediate story recall component of verbal memory was the most affected cognitive function showing a significant decline in its group mean with a large effect size. The best predictors for this change were pre-surgical list learning and Full Scale Intelligence Quotient. These results suggest that non-demented patients, with even mild impairments in both general intellectual functions and list learning, may be at greater risk of decline in other aspects of verbal memory after STN DBS. Pre-existing mild executive dysfunction was not influenced post-operatively. These findings may help selection and consent for STN DBS.     

Effect of deep brain stimulation on caregivers of patients with Parkinson's disease: A systematic review

BackgroundCaregivers of patients with Parkinson's Disease (PD) often provide important support in the pre- and postoperative phase of Deep Brain Stimulation (DBS). DBS-associated changes of patient-functioning may affect caregiver wellbeing and impact the support system. Factors influencing caregiver-wellbeing under these circumstances are incompletely known.Objectiveto systematically review studies of sufficient methodological quality on the impact of DBS on caregivers of PD patients.Methodsusing PRISMA guidelines, major databases were searched up to May 2020. Five subcategories were identified: Caregiver burden, Caregiver cognitive and psychiatric functioning, Caregiver Quality of Life (QoL), Marital Satisfaction/Conflicts, and Caregiver Satisfaction. Quality was assessed using an in-house checklist.Results293 studies were identified; 12 were ultimately included. Caregiver burden, psychiatric and cognitive functioning and QoL remained relatively unchanged. Results on marital satisfaction/conflicts were contrasting: an increase in marital conflicts despite improved relationship quality scores DBS. Caregiver satisfaction with surgery was low with 50–58% of caregivers being disappointed with DBS outcomes. Concerning caregiver related factors: a higher preoperative caregiver QoL, younger age, lower scores on psychiatric rating scales, and more favourable preoperative relationship quality scores, were associated with better caregiver wellbeing. A favourable patient-profile includes younger age and age-at-onset, shorter disease duration, lower medication requirements, and lower scores on psychiatric rating scales.ConclusionAlthough most patient- and caregiver-related subdomains remained unchanged after DBS, dissatisfaction among caregivers and marital problems may constitute a large risk for a well-functioning patient-caregiver dyad. Early recognition of potential problem situations may improve post-DBS care for both patients and caregivers.     

Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in PD

Abstract Objective To compare the cognitive and behavioural effects of unilateral pallidotomy and bilateral subthalamic nucleus (STN) stimulation. Methods After baseline examination 34 patients were randomly assigned to unilateral pallidotomy (4 left-sided, 10 right-sided) or bilateral STN stimulation (n=20). At baseline and six and twelve months after surgery we administered neuropsychological tests of language, memory, visuospatial function, mental speed and executive functions. Also a depression rating scale, and self and proxy ratings of memory and dysexecutive symptoms were administered. Results Six months after surgery, the STN group and the pallidotomy group differed significantly in change from baseline in number of errors on two tests of executive functioning. After 12 months the STN group reported less positive affect compared with baseline than the pallidotomy group. One patient in the STN group showed an overall cognitive deterioration due to complications. Conclusions Although we need larger groups to draw firm conclusions, our results suggest that bilateral STN stimulation has slightly more negative effects on executive functioning than unilateral pallidotomy.     

Risk factors for executive dysfunction after subthalamic nucleus stimulation in Parkinson's disease

A slight decline in cognitive functions and especially in executive functioning after deep brain stimulation (DBS) of the nucleus subthalamicus (STN) in patients with Parkinson's disease (PD) has been described. This study evaluated baseline parameters that contribute to a deterioration of cognitive functioning after DBS. We analyzed data from the neuropsychological protocol in a randomized controlled study comparing DBS with best medical treatment (BMT). Change scores were calculated for the cognitive domains “global cognitive functioning,” “memory,” “working memory,” “attention,” and “executive function.” These domain‐specific change scores were correlated with previously defined preoperative parameters. Compared with the BMT group (63 patients), the STN‐DBS group (60 patients) showed a significant decline only in the domain executive function 6 months after DBS, which was significantly correlated with age, levodopa‐equivalence dosage (LED) and axial subscore of the UPDRS in the off‐medication state at baseline. Multiple regression analysis showed that these three factors explained, however, only about 23% of the variance. Patients with higher age, higher baseline LED, and/or higher axial subscore of the UPDRS at baseline have an increased risk for worsening of executive function after STN‐DBS. High scores of these factors might reflect an advanced stage of disease progression. As these baseline factors explained the variance of the change score executive function only to a minor proportion, other factors including the surgical procedure, the exact placement of the electrode or postsurgical management might be more relevant for a decline in executive functioning after STN‐DBS. © 2010 Movement Disorder Society     

Weight changes associated with unilateral STN DBS and advanced PD

Weight gain following bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson disease (PD) has been characterized previously, but little is known about changes in weight following unilateral STN DBS. Weight gain of approximately 10 kg at one year after bilateral STN DBS for PD has been noted in previous studies, and PD in the absence of DBS has been associated with weight loss. A case-control comparison evaluated the change in weight following unilateral STN DBS in PD. In 39 patients who underwent unilateral STN DBS for PD, we measured the weight change over 1 year versus both preoperative weight change and the weight change in 40 age- and disease severity-matched PD controls without DBS. Regression analyses incorporating age, gender, baseline weight in case or control were conducted to assess weight changes. At 12 months following surgery, the mean weight of unilateral STN DBS patients increased by 4.3 ± 7.2 kg versus the preoperative baseline weight (p < 0.001) and this increase was 4.8 kg compared with the controls (p = 0.015). Over a 1 year time interval, weight gain occurred in 41% of the preoperative unilateral STN DBS patients and 45% of the PD controls, while 85% of the unilateral STN DBS patients had gained weight at 12 months after surgery (p < 0.0001, respectively, chi square test). We conclude that unilateral STN DBS in PD is associated with weight gain, which offsets weight loss associated with advanced PD.     

Cognitive and psychiatric outcome 3 years after globus pallidus pars interna or subthalamic nucleus deep brain stimulation for Parkinson's disease

BackgroundEffects on non-motor symptoms, mainly cognitive and psychiatric side effects, could influence the decision for either globus pallidus pars interna (GPi) or subthalamic nucleus (STN) deep brain stimulation (DBS) for patients with Parkinson's disease (PD).Objective1) To compare cognitive and psychiatric outcomes 3 years after GPi DBS versus STN DBS, and 2) to report on occurrence of suicidal ideation, psychiatric diagnoses, social functioning, and marital satisfaction 3 years after DBS.MethodsPatients were randomized to receive GPi DBS (n = 65) or STN DBS (n = 63). Standardized assessments were performed at baseline, 1 year, and 3 years. We used linear mixed model analyses to investigate between-group differences on the Mattis Dementia Rating Scale (MDRS), neuropsychological tests, and psychiatric questionnaires 3 years after DBS.ResultsEighty-seven patients (68%) completed at least one neuropsychological test after 3 years. No significant between-group differences were found on the MDRS (p = 0.61), neuropsychological tests (p-values between 0.17 and 0.87), and psychiatric questionnaires (p-values between 0.23 and 0.88) 3 years after DBS. The Mini International Neuropsychiatric Interview did not indicate a substantial number of psychiatric diagnoses after 3 years. Social functioning and marital satisfaction were comparable in both groups.ConclusionsThree years after GPi DBS and STN DBS no pronounced between-group differences on measures of cognitive and psychiatric functioning could be demonstrated. Overall, cognitive and psychiatric outcome 3 years after DBS do not provide a clear direction for clinicians when considering which of these two surgical targets to choose.     

Neuropsychological changes 1-year after subthalamic DBS in PD patients: A prospective controlled study

ObjectiveThis study aimed at investigating the neuropsychological effect of DBS of the Subthalamic Nucleus in patients with advanced Parkinson's disease (PD).MethodsA standardized neuropsychological test battery, assessing reasoning, memory and executive functions, was administered to 27 PD patients who underwent DBS-STN (DBS group) and to a matched control group of 31 PD patients under optimal medical treatment (MED group). Patients were evaluated at baseline and at the end of 1 year.ResultsChange score analysis (T1 minus T0 scores) demonstrated a significant decline in phonemic verbal fluency in the DBS group compared with the MED group (p < 0.005), while there were no significant changes between the two groups for the other cognitive tests. Single cases analysis by means of multivariate normative comparisons revealed that 4 out of 27 DBS patients (15%) showed cognitive deterioration one year post surgery. These patients were significantly more compromised from a motor standpoint (UPDRS, section III) than the 23 DBS PD patients who had no cognitive decline post surgery.ConclusionResults of this prospective controlled-study showed that phonemic verbal fluency declined one year after DBS-STN, while the other cognitive domains did not change significantly. Nevertheless, single case analysis highlighted the fact that a subgroup comprising 15% of DBS-STN patients (4/27) showed significant cognitive decline 1 year after surgery.     

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: comparison of pre- and postoperative neuropsychological evaluation.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of advanced Parkinson's disease (PD). The aim of this study was to assess the effect of the bilateral surgical procedure and STN DBS on the neuropsychological functions. Twenty Parkinson's disease patients underwent a neuropsychological assessment before and 6 months after surgery in four different conditions: medication on (with levodopa) and medication off (without levodopa) during the preoperative period, medication on/stimulation on (levodopa plus stimulators switched on) and medication off/stimulation on (stimulators switched on without levodopa) during the postoperative period. We did not find any significant difference in the four conditions for all the neuropsychological tests, confirming the lack of an overall cognitive decline after surgery. From a neuropsychological point of view, these results seem to indicate that bilateral STN DBS is a safe treatment for advanced PD.     

Cognitive effects of theta frequency bilateral subthalamic nucleus stimulation in Parkinson’s disease: A pilot study

BackgroundThere is significant evidence for cognitive decline following deep brain stimulation (DBS). Current stimulation paradigms utilize gamma frequency stimulation for optimal motor benefits; however, little has been done to optimize stimulation parameters for cognition. Recent evidence implicates subthalamic nucleus (STN) theta oscillations in executive function, and theta oscillations are well-known to relate to episodic memory, suggesting that theta frequency stimulation could potentially improve cognition in Parkinson’s disease (PD).ObjectiveTo evaluate the acute effects of theta frequency bilateral STN stimulation on executive function in PD versus gamma frequency and off, as well as investigate the differential effects on episodic versus nonepisodic verbal fluency.MethodsTwelve patients (all males, mean age 60.8) with bilateral STN DBS for PD underwent a double-blinded, randomized cognitive testing during stimulation at (1) 130–135 Hz (gamma), (2) 10 Hz (theta) and (3) off. Executive functions and processing speed were evaluated using verbal fluency tasks (letter, episodic category, nonepisodic category, and category switching), color-word interference task, and random number generation task. Performance at each stimulation frequency was compared within subjects.ResultsTheta frequency significantly improved episodic category fluency compared to gamma, but not compared to off. There were no significant differences between stimulation frequencies in other tests.ConclusionIn this pilot trial, our results corroborate the role of theta oscillations in episodic retrieval, although it is unclear whether this reflects direct modulation of the medial temporal lobe and whether similar effects can be found with more canonical memory paradigms. Further work is necessary to corroborate our findings and investigate the possibility of interleaving theta and gamma frequency stimulation for concomitant motor and cognitive effects.     

Neuropsychological performance following staged bilateral pallidal or subthalamic nucleus deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) has the potential to significantly reduce motor symptoms in advanced Parkinson's disease (PD). Controversy remains about non-motor effects of DBS and the relative advantages of treatment at two brain targets, the globus pallidus internus (GPi) and the subthalamic nucleus (STN). We investigated effects of DBS on neuropsychological functioning in 42 patients with advanced PD randomly assigned to receive staged bilateral DBS surgery of either the GPi or STN. Patients underwent neuropsychological assessment prior to and 6 months after unilateral surgery. Twenty-nine subsequently underwent surgery to the contralateral side and completed a second follow-up neuropsychological evaluation 15 months later. Unilateral treatment resulted in small but statistically significant reductions in performance on several measures, including verbal fluency and working memory. A similar pattern was observed after bilateral treatment. Reductions in verbal associative fluency were significant only after left-sided treatment. There were few significant differences related to treatment at the two surgical targets. Supplementary analyses suggested that decrements in select neuropsychological domains following DBS are unrelated to age or post-surgical reduction in dopaminergic medication dose. Findings are discussed with reference to possible causes of neuropsychological decline and the need for further controlled studies of specific neuropsychological effects of DBS.     

Acute low frequency dorsal subthalamic nucleus stimulation improves verbal fluency in Parkinson's disease

BackgroundParkinson's disease (PD) is a common neurodegenerative disorder that results in movement-related dysfunction and has variable cognitive impairment. Deep brain stimulation (DBS) of the dorsal subthalamic nucleus (STN) has been shown to be effective in improving motor symptoms; however, cognitive impairment is often unchanged, and in some cases, worsened particularly on tasks of verbal fluency. Traditional DBS strategies use high frequency gamma stimulation for motor symptoms (∼130 Hz), but there is evidence that low frequency theta oscillations (5–12 Hz) are important in cognition.MethodsWe tested the effects of stimulation frequency and location on verbal fluency among patients who underwent STN DBS implantation with externalized leads. During baseline cognitive testing, STN field potentials were recorded and the individual patients’ peak theta frequency power was identified during each cognitive task. Patients repeated cognitive testing at five different stimulation settings: no stimulation, dorsal contact gamma (130 Hz), ventral contact gamma, dorsal theta (peak baseline theta) and ventral theta (peak baseline theta) frequency stimulation.ResultsAcute left dorsal peak theta frequency STN stimulation improves overall verbal fluency compared to no stimulation and to either dorsal or ventral gamma stimulation. Stratifying by type of verbal fluency probes, verbal fluency in episodic categories was improved with dorsal theta stimulation compared to all other conditions, while there were no differences between stimulation conditions in non-episodic probe conditions.ConclusionHere, we provide evidence that dorsal STN theta stimulation may improve verbal fluency, suggesting a potential possibility of integrating theta stimulation into current DBS paradigms to improve cognitive outcomes.     

Deep brain stimulation of the subthalamic nucleus improves intrinsic alertness in Parkinson's disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a treatment option for patients with Parkinson's disease (PD) in the advanced stage. Besides motor improvement, DBS of the STN may also modulate cognitive and attentional functions of the basal ganglia. In our study, 13 patients with PD and bilateral DBS of the STN were assessed with DBS switched on and off by the use of a wide range of neuropsychological tasks. This included reasoning, cognitive flexibility, phonemic and semantic word fluency, verbal and nonverbal short‐term memory, learning, delayed verbal memory recall, and stimulus‐response incompatibility. Special emphasis was put on basic attentional functions, in particular intrinsic and phasic alertness as well as visual search. DBS significantly improved intrinsic alertness, whereas phasic alertness and other neuropsychological domains were not affected. Additionally, the effects on intrinsic alertness were independent of motor improvements by DBS. The findings suggest that DBS modulates the fronto‐parietal network of alertness. © 2009 Movement Disorder Society     

Impaired performance on the Wisconsin Card Sorting Test under left- when compared to right-sided deep brain stimulation of the subthalamic nucleus in patients with Parkinson’s disease

Over the past decade, deep brain stimulation (DBS) has become an effective treatment option for managing severe Parkinson’s disease (PD). However, evidence is accumulating that DBS of target sites like the subthalamic nucleus (STN) can result in unintended cognitive effects that lie beyond motor control. The aim of the present study was to evaluate whether changes in executive task performance after chronic DBS might be predominantly associated with the stimulation of only one hemisphere. Eight patients with PD who had undergone DBS treatment of the STN were selected to participate in the study. Using a repeated measurements design, they underwent a neuropsychological examination under unilateral left- and right-sided stimulation in order to investigate laterality effects in their performance on the Wisconsin Card Sorting Test. All patients showed a significant improvement in motor symptoms postoperatively. Selected aspects of executive task performance were compromised under left- when compared to right-sided stimulation. Performance measures were unrelated to demographic, neurological, and behavioral characteristics of the patients. Findings are consistent with the emerging evidence that the STN is not only involved in motor control, but also participates in functions of the cognitive domain. Moreover, results raise the possibility that the left and right hemisphere might differ in their vulnerability to tolerate side effects on executive functions of DBS treatment. Potential consequences for future research questions and the management of cognitive side effects are discussed.     

Subthalamic nucleus deep brain stimulation changes speech respiratory and laryngeal control in Parkinson’s disease

Adequate respiratory and laryngeal motor control are essential for speech, but may be impaired in Parkinson’s disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on respiratory and laryngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of respiratory and laryngeal control, and whether these changes were correlated with limb function and stimulation parameters. Eighteen PD participants with bilateral STN DBS were tested within a morning session after a minimum of 12 h since their most recent dose of anti-PD medication. Testing occurred when DBS was on, and again 1 h after DBS was turned off, and included aerodynamic measures during syllable production, and standard clinical ratings of limb function. We found that PD participants exhibited changes with DBS, consistent with increased respiratory driving pressure (n = 9) and increased vocal fold closure (n = 9). However, most participants exceeded a typical operating range for these respiratory and laryngeal control variables with DBS. Changes were uncorrelated with limb function, but showed some correlation with stimulation frequency and pulse width, suggesting that speech may benefit more from low-frequency stimulation and shorter pulse width. Therefore, high-frequency STN DBS may be less beneficial for speech-related respiratory and laryngeal control than for limb motor control. It is important to consider these distinctions and their underlying mechanisms when assessing the impact of STN DBS on PD.