Deep Brain Stimulation Of The Subthalamic Nucleus Research Articles

Deep brain stimulation of the subthalamic nucleus modulates reward processing and action selection in Parkinson patients

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for motor impairments in Parkinson's disease (PD) but its effect on the motivational regulation of action control is still not fully understood. We investigated whether DBS of the STN influences the ability of PD patients to act for anticipated reward or loss, or whether DBS improves action execution independent of motivational valence. 16 PD patients (12 male, mean age = 58.5 ± 10.17 years) treated with bilateral STN-DBS and an age- and gender-matched group of healthy controls (HC) performed a go/no-go task whose contingencies explicitly decouple valence and action. Patients were tested with (ON) and without (OFF) active STN stimulation. For HC, there was a benefit in performing rewarded actions when compared to actions that avoided punishment. PD patients showed such a benefit reliably only when STN stimulation was ON. In fact, the relative behavioral benefit for go for reward over go to avoid losing was stronger in the PD patients under DBS ON than in HC. In PD patients, rather than generally improving motor functions independent of motivational valence, modulation of the STN by DBS improves action execution specifically when rewards are anticipated. Thus, STN-DBS establishes a reliable congruency between action and reward ("Pavlovian congruency") and remarkably enhances it over the level observed in HC.

Where and what is the PPN and what is its role in locomotion?

This scientific commentary refers to ‘The integrative role of the pedunculopontine nucleus in human gait’, by Lau et al. (doi:10.1093/brain/awv047). Parkinson’s disease is a progressive neurodegenerative disorder characterized by bradykinesia, rigidity and tremor, and dopamine replacement with levodopa remains the mainstay of treatment. In recent years, deep brain stimulation of the subthalamic nucleus (STN) has been widely used to treat tremor, rigidity and akinesia (Benabid et al. , 2009). However as the disease progresses, axial symptoms such as postural instability and gait disturbances often emerge, in particular freezing of gait (FOG). These gait disturbances are poorly responsive to dopamine therapy and to deep brain stimulation of the STN (Ferraye et al. , 2010). FOG is very debilitating, often leading to falls and having a severe impact on quality of life. Patients describe FOG as ‘like having feet that are glued to the floor’ and a 2010 workshop on FOG described it as ‘brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk’. Moreover, these disturbances of gait are responsive to sensory stimuli. For example, FOG is accentuated when approaching doorways and can be alleviated by …

Comment: New insights on cognition after deep brain stimulation in Parkinson disease.

Long-lasting concern lingers about cognitive decline following deep brain stimulation (DBS) in Parkinson disease (PD).1 DBS of the subthalamic nucleus (STN) in particular has been associated with unfavorable neuropsychological outcomes, but robust controlled data comparing STN and globus pallidus internus (GPi) are limited.

Surviving 10 years with deep brain stimulation for Parkinson's disease--a follow-up of 79 patients.

Deep brain stimulation (DBS) for severe Parkinson's disease (PD) outperforms the best medical treatment in controlling motor symptoms and improving quality of life. Nevertheless disease progression cannot be controlled, and the development of dementia over time is nearly inevitable, often resulting in nursing home placement. Ten-year survival, development of hallucinations, dementia and nursing home placement were examined and adverse events were assessed. Patient files were scrutinized from baseline up to 10 years of treatment or death on all 79 PD patients treated with DBS of the subthalamic nucleus from 1998 to 2003 at Aarhus University Hospital. Twenty-four patients died during the follow-up period of 10 years. Age above 60 years at surgery increased mortality 2.3-fold (P = 0.04). Of the 55 surviving patients 29 (53%) were demented and 19 (35%) were in nursing homes. Average time from operation to dementia was 5.6 ± 2.9 years. Hallucinations and nursing home placement were associated with increased mortality. Survival of 70% after a mean of 25 years of PD including 10 years with DBS illustrates that this is a selected group of PD patients. The prevalence of dementia steadily increased after surgery as expected from disease progression and can be an early event. Compared with the few similar long-term studies, the present study presents a larger cohort followed at the same DBS center for a longer period of time and none was lost to follow-up, making conclusions more valid. The present findings are of significant prognostic help for the patient, caregiver and physician when treatment with DBS has to be decided.

2014 Lasker-DeBakey Clinical Medical Research Award.

2014 Lasker-DeBakey Clinical Medical Research Award.

The effects of subthalamic nucleus stimulation on semantic and syntactic performance in spontaneous language production in people with Parkinson's disease

Abstract Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an established therapeutic option for advanced Parkinson's disease (PD). In this study, the effects of unilateral and bilateral STN stimulation on spontaneous language production are explored, by comparing linguistic performance in different stimulation conditions with normative data of healthy subjects. Language samples of ten PD patients with DBS of the STN were obtained in four stimulation conditions: bilateral stimulation on, bilateral stimulation off, stimulation of the left STN only and stimulation of the right STN only. The spontaneous language production differed from the normative data in all four stimulation conditions. Especially morphosyntactic elements of spontaneous language production were altered. Despite these linguistic differences with normal controls no significant differences between stimulation conditions were found. These results emphasize that the effects of STN stimulation on spontaneous language production reflect a complex interplay of multiple factors.

Depression and anxiety following deep brain stimulation in Parkinson's disease: systematic review and meta-analysis.

Deep brain stimulation (DBS) is effective in advanced Parkinson's disease (PD), improving motor symptoms, fluctuations and quality of life. However, adverse psychiatric outcomes have been reported, albeit variably and in an unstandardized fashion. We aimed to summarize the published evidence on the outcomes of anxiety and depressive symptoms in Parkinson's disease patients following DBS, through systematic review and meta-analysis. PubMed was searched until May 2012 to identify studies assessing anxiety and depressive symptoms in PD patients who underwent bilateral DBS of the subthalamic nucleus (STN) or globus pallidus internus (GPi). Random effects metaanalyses were conducted for groups of at least three studies that were homogeneous regarding the design and the instruments used. 63 references were selected; 98.4% provided data on depression, and 38.1% on anxiety assessment scales. Two studies did not discriminate the target; from the remaining 61 references, short-term evaluation was performed in 37 (60.7%), mid-term in 36 (59.0%) and long-term in 5 (8.2%). Data on pre to postop variation was available in 57 (93.4%) reports and 16 (26.2%) presented STNDBS versus different comparison groups: GPi-DBS (n = 4 studies, 25.0%), eligible for surgery (n = 6, 37.5%), and medical treatment (n = 7, 43.8%). Improvement of depression and anxiety is apparent after DBS, more pronounced in the short-term, an effect that seems to wane in later assessments. Concerning depression, STN-DBS shows superiority against medical treatment, but not when compared to eligible for surgery control groups. The opposite is apparent for anxiety, as results favor medical treatment over STN-DBS, and STNDBS over eligible for surgery control group. Superiority of one target over the other is not evident from the results, but data slightly favors GPi for both outcomes. The pattern and course of depressive symptoms and anxiety following DBS in PD is not clear, although both seem to improve in the short-term, especially depression following STN-DBS. RESULTS are highly heterogeneous. Efforts should be carried out to standardize assessment procedures across centers. Parkinson's Disease; Deep Brain Stimulation; Anxiety; Depression; Meta-Analysis.

Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease.

Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry, alters basal endogenous glucose production (EGP) or insulin sensitivity in patients with Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in the basal state and during a hyperinsulinemic euglycemic clamp using a stable glucose isotope, in the stimulated and non-stimulated condition. We measured EGP, hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP did not differ between the stimulated and non-stimulated condition. Hepatic insulin sensitivity was similar in both conditions and there were no significant differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off. UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in patients with PD does not influence basal EGP or insulin sensitivity. These results suggest that acute modulation of the motor basal ganglia circuitry does not affect glucose metabolism in humans.

Optimal target localization for subthalamic stimulation in patients with Parkinson disease

Objective:To further determine the causes of variable outcome from deep brain stimulation of the subthalamic nucleus (DBS-STN) in patients with Parkinson disease (PD).Methods:Data were obtained from our cohort of 309 patients with PD who underwent DBS-STN between 1996 and 2009. We examined the relationship between the 1-year motor, cognitive, and psychiatric outcomes and (1) preoperative PD clinical features, (2) MRI measures, (3) surgical procedure, and (4) locations of therapeutic contacts.Results:Pre- and postoperative results were obtained in 262 patients with PD. The best motor outcome was obtained when stimulating contacts were located within the STN as compared with the zona incerta (64% vs 49% improvement). Eighteen percent of the patients presented a postoperative cognitive decline, which was found to be principally related to the surgical procedure. Other factors predictive of poor cognitive outcome were perioperative confusion and psychosis. Nineteen patients showed a stimulation-induced hypomania, which was related to both the form of the disease (younger age, shorter disease duration, higher levodopa responsiveness) and the ventral contact location. Postoperative depression was more frequent in patients already showing preoperative depressive and/or residual axial motor symptoms.Conclusion:In this homogeneous cohort of patients with PD, we showed that (1) the STN is the best target to improve motor symptoms, (2) postoperative cognitive deficit is mainly related to the surgery itself, and (3) stimulation-induced hypomania is related to a combination of both the disease characteristics and a more ventral STN location.

Epidemiological Profile and Satisfaction Assessment of Patients with Parkinson s Disease After Implantation of DBS

Introduction: Parkinson’s disease is a neurodegenerative disorder characterized mainly by motor impairment, with sensory, autonomic cognitive-behavioral and sleep-related symptoms. Dopaminergic medications can alleviate a subset of these symptoms. Deep Brain Stimulation (DBS) improves motor symptoms and quality of life in Parkinson’s disease with the most important advantage of maintenance of a constant level of stimulation throughout the day. Objective: To determine the profile and perception of results of patients who underwent implantation of DBS for Parkinson’s disease in a tertiary neurological hospital. Methods: Patients who had a diagnosis of Parkinson’s disease and were submitted to implantation of DBS between May 2010 and December 2013, in our service, were included in a retrospective analysis. Medical records were reviewed and, via telephone contact, they responded to a questionnaire on their perception of the procedure and its results. Results: Twenty-one procedures were performed for implantation of DBS in patients with Parkinson’s disease. All patients were evaluated at least one year after the procedure. Average age at implantation was 64.42 years (29% female, 71% male). Seventeen patients could be contacted of the 21 selected patients (1 patient was deceased and 3 were not possible to reach). Seventy-one percent would agree to be submitted to the procedure again and 76% would recommend it to someone else. Discussion: DBS of the subthalamic nucleus (STN) relieves motor fluctuations and dyskinesias associated with Parkinson’s disease, with sustained benefit. Treatment with DBS has good outcome in most patients and is a good therapeutic option to be considered in selected cases. Further researches with larger samples can aid in the improvement of the treatment offered to patients with Parkinson’s disease for a better quality of life.

Subthalamotomy in the treatment of Parkinson's disease: clinical aspects and mechanisms of action

Parkinson's disease (PD) is a neurodegenerative condition that can be pharmacologically treated with levodopa. However, important motor and nonmotor symptoms appear with its long-term use. The subthalamic nucleus (STN) is known to be involved in the pathophysiology of PD and to contribute to levodopa-induced complications. Surgery is considered in patients who have advanced PD that is refractory to pharmacotherapy and who display disabling dyskinesia. Deep brain stimulation of the STN is currently the main surgical procedure for PD, but lesioning is still performed. This review covers the clinical aspects and complications of subthalamotomy as one of the lesion-based options for PD patients with levodopa-induced dyskinesias. Moreover, the authors discuss the possible effects of subthalamic lesioning.

The added value of semimicroelectrode recording in deep brain stimulation of the subthalamic nucleus for Parkinson disease

Accurate placement of the leads is crucial in deep brain stimulation (DBS). To optimize the surgical positioning of the lead, a combination of anatomical targeting on MRI, electrophysiological mapping, and clinical testing is applied during the procedure. Electrophysiological mapping is usually done with microelectrode recording (MER), but the relatively undocumented semimicroelectrode recording (SMER) is a competing alternative. In this study the added value and safety of SMER for optimal lead insertion in the subthalamic nucleus (STN) in a consecutive cohort of patients with Parkinson disease (PD) was assessed. Between 2001 and 2010, a consecutive single-center cohort of 46 patients with PD underwent DBS of the STN (85 lead insertions). After exclusion of 11 lead insertions for mostly technical reasons, 74 insertions were included for the assessment. Anatomical target localization was based on either 1.5-T MRI or fused 3-T MRI with CT, with reference to anterior commissure-posterior commissure coordinates. Electrophysiological mapping was performed with SMER. Intraoperative clinical testing was dominant in determining the final lead position. The target error was defined as the absolute distance between the anatomical or electrophysiological target and the final lead position. The effect of SMER on anatomical target error reduction and final target selection was analyzed. Also, the anatomical and electrophysiological target error was judged against the different imaging strategies. For safety evaluation, the adverse events related to all lead insertions were assessed. The use of SMER significantly reduced the anatomical target error from 1.7 (SD 1.6) mm to 0.8 (SD 1.3) mm (p < 0.0001). In particular, the anatomical target error based on 1.5-T MRI was significantly reduced by SMER, from 2.3 (SD 1.5) mm to 0.1 (SD 0.5) mm (p < 0.001). Anatomical target error reduction based on 3-T MRI fused with CT was not significantly influenced by SMER (p = 0.2), because the 3-T MRI-CT combination already significantly reduced the anatomical target error from 2.3 (SD 1.5) mm to 1.5 (SD 1.5) mm compared with 1.5-T MRI (p = 0.03). No symptomatic intracerebral hemorrhage was reported. Intracerebral infection was encountered in 1 patient following lead insertion. Semimicroelectrode recording has added value in targeting the STN in DBS for patients with PD based on 1.5-T MRI. The use of SMER does not significantly reduce the anatomical target error in procedures with fused 3-T MRI-CT studies and therefore might be omitted. With the absence of hemorrhagic complications, SMER-guided lead implantation should be considered a safe alternative to MER.

A manic episode after bilateral subthalamic stimulation in a patient with advanced Parkinson's disease.

Deep brain stimulation (DBS) has proven to be an effective treatment for patients with refractory symptoms in the advanced stages of Parkinson's disease. However, different psychiatric and cognitive problems may occur after DBS. We report a case of a manic episode after DBS of the subthalamic nucleus in a patient with advanced Parkinson's disease. After slow and gradually restart of the neurostimulation using the lowest effective intensity, the motor symptoms remained sufficiently under control without causing any psychiatric problems.

Adaptive deep brain stimulation in advanced Parkinson disease

Objective: Brain–computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof-of-principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS.Methods: We tested BCI-controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson's Disease Rating Scale.Results: Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27% (p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements (p < 0.001). aDBS was also more effective than no stimulation and random intermittent stimulation.Interpretation BCI-controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD. Ann Neurol 2013;74:449–457

Locus Coeruleus Is Involved in Weight Loss in a Rat Model of Parkinson's Disease: An Effect Reversed by Deep Brain Stimulation

IntroductionIn Parkinson's disease (PD) weight loss is a secondary phenomenon to the progressive neurodegeneration that changes after deep brain stimulation of the subthalamic nucleus (DBS-STN) leading to increased weight gain. The mechanism responsible for this profile in weight variation may be secondary to a central metabolic control influenced by the noradrenergic system. In this study authors evaluate the effect of additional noradrenergic neuronal degeneration, namely of the locus coeruleus (LC), on weight variation in the 6-hydroxydopamine (6-OHDA) rat model of PD. Material and methodsAn experimental group of parkinsonian animals with additional 6-OHDA lesion of the LC was developed to analyze the effect of this lesion on the metabolic state of rats before and after DBS-STN. Rats were placed in metabolic cages for evaluation of weight, food and liquid intake and urine and fecal volume, before and after DBS-STN. The effects of 6-OHDA lesions and DBS-STN on motor behavior were also monitored. Tissue levels of monoamines in the striatum of 6-OHDA-lesioned animals and catecholamine levels in urine and plasma were evaluated. ResultsIn the experimental group of Parkinsonian animals with 6-OHDA degeneration of the striatum alone, no effects on weight gain, food intake and other metabolic parameters were observed before or after DBS-STN. Additional lesion of the LC produced a significant decrease in weight gain with a trend toward a decrease in solid intake. Chronic DBS-STN in rats with LC and striatum degeneration abolished the weight loss without producing changes to food intake and other metabolic parameters. Additional degeneration of the LC was not accompanied by significant changes in motor behavior but produced an additional decrease in striate monoamines levels namely a decrease in the DA/l-DOPA ratio. ConclusionsIn PD degeneration of noradrenergic neurons, in particular of the LC, may be required to observe side effects unrelated to motor symptoms such as body weight deregulation. Our results support the notion that the LC may be important in maintaining the activity of the nigrostriatal dopamine pathways, and thus play a crucial role in weight variation in a PD.

Urinary profile of catecholamines and metabolites in Parkinson patients with deep brain stimulation

Deep brain stimulation of the subthalamic nucleus (DBS-STN) is thought to continuously alter the activity of STN neurons in Parkinson's disease (PD). A chronic decrease in the levodopa dose with continuous STN stimulation may induce plastic neuronal changes. The objective of this work was to study urinary excretion of catecholamines in patients with PD before and after DBS-STN. Twenty-three patients were submitted to DBS-STN, and evaluated before and after surgery with respect to catecholamines and metabolites in 24-h urine measured by high-performance liquid chromatography with electrochemical detection. Of the 23 patients evaluated, a significant decrease of about 60% in the urinary excretion of L-3,4-dihydroxyphenylalanine (L-DOPA; in nmol/mg creatinine/24 h) was observed 1 week after DBS-STN. Moreover, in 17 patients with a follow-up of 8 weeks after surgery, there was a further 50% decrease in urinary L-DOPA levels, dropping to about 75% of the values before surgery. There was also a significant decrease in dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels 1 week after DBS-STN that was no longer present 8 weeks after. A significant increase in the DA/l-DOPA ratio was observed 1 week after surgery, with a further increase 8 weeks after surgery. After DBS-STN, the DA/l-DOPA ratio, an indirect measure of DA synthesis, increased. These results show that DBS-STN may improve the efficacy of oral levodopa.

Bilateral stimulation of the subthalamic nucleus has differential effects on reactive and proactive inhibition and conflict-induced slowing in Parkinson’s disease

It has been proposed that the subthalamic nucleus (STN) mediates response inhibition and conflict resolution through the fronto-basal ganglia pathways. Our aim was to compare the effects of deep brain stimulation (DBS) of the STN on reactive and proactive inhibition and conflict resolution in Parkinson's disease using a single task. We used the conditional Stop signal reaction time task that provides the Stop signal reaction time (SSRT) as a measure of reactive inhibition, the response delay effect (RDE) as a measure of proactive inhibition and conflict-induced slowing (CIS) as a measure of conflict resolution. DBS of the STN significantly prolonged SSRT relative to stimulation off. However, while the RDE measure of proactive inhibition was not significantly altered by DBS of the STN, relative to healthy controls, RDE was significantly lower with DBS off but not DBS on. DBS of the STN did not alter the mean CIS but produced a significant differential effect on the slowest and fastest RTs on conflict trials, further prolonging the slowest RTs on the conflict trials relative to DBS off and to controls. These results are the first demonstration, using a single task in the same patient sample, that DBS of the STN produces differential effects on reactive and proactive inhibition and on conflict resolution, suggesting that these effects are likely to be mediated through the impact of STN stimulation on different fronto-basal ganglia pathways: hyperdirect, direct and indirect.

Bilateral deep brain stimulation of the subthalamic nucleus effectively relieves dystonia secondary to Fahr's disease: a case report

Fahr's disease (FD) is a rare movement disorder characterized by bilateral intracranial calcifications that is refractory to most treatments. We present the case of a 26-year-old male with FD who was unable to walk independently and could not eat solid food because of poor swallowing capability and severe cervical dystonia. Injections of botulin toxin into the neck muscles, as well as biperiden, tiapride, amantadine, L-dopa and clonazepam were ineffective. Deep brain stimulation (DBS) was performed with two permanent electrodes containing four contact sites implanted bilaterally into the subthalamic nucleus (STN). The antidystonic effect was evident immediately after STN stimulation, and it was sustained during a 24-month follow-up period. There was a marked reduction of cervical dystonia, and he could eat solid food and was able to walk independently. This case demonstrates that DBS of the STN can be effective for the treatment of dystonia associated with FD.

Evaluation of Metabolic State in Striatal Rat Model of Parkinson’s Disease: before and after Deep Brain Stimulation

Weight loss occurs during the natural history of Parkinson’s disease (PD). This non-motor manifestation of the disease is reversed by deep brain stimulation of the sub thalamic nucleus (DBS-STN) therapeutics which is often associated with weight gain. Although it has been proposed that PD is associated with alterations in central energy metabolism the mechanisms responsible for this weight variation remain unknown. This study evaluates the weight profile and nutritional state of the 6-hydroxydopamine (6-OHDA) rat model of PD subjected to DBS-STN. Rats were rendered parkinsonian by bilateral injections of 6-OHDA into the striatum and electrodes were implanted bilaterally at the level of the STN. Rats were placed in metabolic cages for evaluation of weight, food and liquid intake and urine and fecal volume before and 2 and 4 weeks after the beginning of stimulation. Before stimulation began (2 weeks after 6-OHDA lesion), weight and metabolic parameters were similar between parkinsonian rats with and without electrodes and matched control rats. Two weeks after stimulation began (4 weeks after 6-OHDA lesion) and at the end of the study, 4 weeks after stimulation began (6 weeks after 6-OHDA lesion), body weight and the metabolic parameters evaluated remained unaltered between animal groups. Furthermore, at the end of the study, no statistically significant differences were found in efficiency of eating (change in weight/amount of food eaten) or weight gain between groups. In conclusion, in the rat model of PD with striatal dopaminergic neurodegeneration neither induction of PD or DBS-STN influenced weight variation or metabolic state. Additional mechanisms may be required to induce the altered metabolic state observed in PD patients before and after STN-DBS.

Neuropsychological effects of deep brain stimulation for Parkinson′s disease

Background:Putative changes of cognition after deep brain stimulation (DBS) in patients with Parkinson's disease (PD) are a matter of debate. The aim of this study was to assess cognitive abilities before and following bilateral subthalamic nucleus (STN) DBS and to review the available literature.Methods:Twenty patients underwent bilateral DBS of the STN. Cognitive skills were assessed in a standardized fashion before and at least at 12 months after the surgical intervention.Results:There was a significant decline of both semantic and phonematic verbal fluency and a mild trend for a deterioration of verbal memory after DBS. Mood, general cognitive screening, and visospatial abilities remained unchanged.Conclusion:STN DBS in the treatment of PD has resulted in a significant reduction of motor symptoms and improved independence and quality of life in appropriately selected patients. However, it may have isolatable effects on verbal fluency and related function. Case series in the literature reported similar findings. Potential candidates for DBS should be counseled about the risk of mild cognitive declines.