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    Steering the Volume of Tissue Activated With a Directional Deep Brain Stimulation Lead in the Globus Pallidus Pars Interna: A Modeling Study With Heterogeneous Tissue Properties. Zhang Simeng,Tagliati Michele,Pouratian Nader,Cheeran Binith,Ross Erika,Pereira Erlick Frontiers in computational neuroscience To study the effect of directional deep brain stimulation (DBS) electrode configuration and vertical electrode spacing on the volume of tissue activated (VTA) in the globus pallidus, pars interna (GPi). Directional DBS leads may allow clinicians to precisely direct current fields to different functional networks within traditionally targeted brain areas. Modeling the shape and size of the VTA for various monopolar or bipolar configurations can inform clinical programming strategies for GPi DBS. However, many computational models of VTA are limited by assuming tissue homogeneity. We generated a multimodal image-based detailed anatomical (MIDA) computational model with a directional DBS lead (1.5 mm or 0.5 mm vertical electrode spacing) placed with segmented contact 2 at the ventral posterolateral "sensorimotor" region of the GPi. The effect of tissue heterogeneity was examined by replacing the MIDA tissues with a homogeneous tissue of conductance 0.3 S/m. DBS pulses (amplitude: 1 mA, pulse width: 60 μs, frequency: 130 Hz) were used to produce VTAs. The following DBS contact configurations were tested: single-segment monopole (2B-/Case+), two-segment monopole (2A-/2B-/Case+ and 2B-/3B-/Case+), ring monopole (2A-/2B-/2C-/Case+), one-cathode three-anode bipole (2B-/3A+/3B+/3C+), three-cathode three-anode bipole (2A-/2B-/2C-/3A+/3B+/3C+). Additionally, certain vertical configurations were repeated with 2 mA current amplitude. Using a heterogeneous tissue model affected both the size and shape of the VTA in GPi. Electrodes with both 0.5 mm and 1.5 mm vertical spacing (1 mA) modeling showed that the single segment monopolar VTA was entirely contained within the GPi when the active electrode is placed at the posterolateral "sensorimotor" GPi. Two segments in a same ring and ring settings, however, produced VTAs outside of the GPi border that spread into adjacent white matter pathways, e.g., optic tract and internal capsule. Both stacked monopolar settings and vertical bipolar settings allowed activation of structures dorsal to the GPi in addition to the GPi. Modeling of the stacked monopolar settings with the DBS lead with 0.5 mm vertical electrode spacing further restricted VTAs within the GPi, but the VTA volumes were smaller compared to the equivalent settings of 1.5 mm spacing. 10.3389/fncom.2020.561180
    The effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) on cognition in Parkinson disease. Heo Jae-Hyeok,Lee Kyoung-Min,Paek Sun Ha,Kim Min-Jeong,Lee Jee-Young,Kim Ji-Young,Cho Soo-Young,Lim Yong Hoon,Kim Mi-Ryoung,Jeong Soo Yeon,Jeon Beom S Journal of the neurological sciences The effects of subthalamic nucleus (STN) stimulation on cognition and mood have not been well established. The authors estimated cognitive and mood effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinson's disease (PD) at 6 months and 1 year postoperatively. Forty-six patients were recruited from the Movement Disorder Center at Seoul National University Hospital. Neuropsychologic tests were performed three times, before, 6 months after, and 1 year after surgery. Mean patient age was 58 and mean education duration 8 years. Eighteen of the 46 patients were men. The instruments used for assessing cognitive functions were; the Mini-Mental Status Examination (MMSE), the Trail Making Test (TMT), the Korean Boston Naming Test (K-BNT), the Rey-Kim Memory Battery, the Grooved pegboard test, the Stroop test, a fluency test, the Wisconsin Card Sorting test (WCST), and the Beck depression inventory (BDI). Of these tests, the verbal memory test, the Stroop test, and the fluency test showed statistically significant changes. The verbal memory test using the Rey-Kim memory battery showed a decline in delayed recall and recognition at 6 months and 1 year postoperatively, whereas nonverbal memory showed no meaningful change. In terms of frontal lobe function tests, Stroop test and fluency test findings were found to be aggravated at 6 months and this continued at 1 year postoperatively. Previous studies have consistently reported a reduction in verbal fluency and improvements in self-reported symptoms of depression after STN DBS. However, in the present study, Beck depression inventory (B.D.I.) was not significantly changed. Other tests, namely, MMSE, TMT, K-BNT, Grooved pegboard test, and the WCST also failed to show significant changes. Of the baseline characteristics, age at onset, number of years in full-time education, and L-dopa equivalent dosage were found to be correlated with a postoperative decline in neuropsychological test results. The correlation of motor improvement and cognitive deterioration was not significant, which suggests that the stimulation effect is rather confined to the motor-related part in the STN. In conclusion, bilateral STN DBS in Parkinson's disease did not lead to a significant global deterioration in cognitive function. However, our findings suggest that it has minor detrimental long-term impacts on memory and frontal lobe function. 10.1016/j.jns.2008.06.010
    Deep brain stimulation and recordings: Insights into the contributions of subthalamic nucleus in cognition. Drummond Neil M,Chen Robert NeuroImage Recent progress in targeted interrogation of basal ganglia structures and networks with deep brain stimulation in humans has provided insights into the complex functions the subthalamic nucleus (STN). Beyond the traditional role of the STN in modulating motor function, recognition of its role in cognition was initially fueled by side effects seen with STN DBS and later revealed with behavioral and electrophysiological studies. Anatomical, clinical, and electrophysiological data converge on the view that the STN is a pivotal node linking cognitive and motor processes. The goal of this review is to synthesize the literature to date that used DBS to examine the contributions of the STN to motor and non-motor cognitive functions and control. Multiple modalities of research have provided us with an enhanced understanding of the STN and reveal that it is critically involved in motor and non-motor inhibition, decision-making, motivation and emotion. Understanding the role of the STN in cognition can enhance the therapeutic efficacy and selectivity not only for existing applications of DBS, but also in the development of therapeutic strategies to stimulate aberrant circuits to treat non-motor symptoms of Parkinson's disease and other disorders. 10.1016/j.neuroimage.2020.117300
    Predictors of cognitive and psychosocial outcome after STN DBS in Parkinson's Disease. Smeding Harriet M M,Speelman Johannes D,Huizenga Hilde M,Schuurman P Richard,Schmand Ben Journal of neurology, neurosurgery, and psychiatry OBJECTIVE:To find predictors of cognitive decline and quality of life 1 year after bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson's disease (PD). METHODS:A total of 105 patients were evaluated with a comprehensive neuropsychological assessment before and 12 months after surgery. A control group of 40 PD patients was included to control for effects of repeated testing and disease progression. The authors determined individual changes in cognition, mood and quality of life using a statistical method that controls for multiple comparisons, and performed logistic regression analyses to assess predictors of cognitive changes and quality of life. RESULTS:12 months after surgery, the improvement in motor function was 41% (Unified Parkinson's Disease Rating Scale Part 3 score in off). The STN group showed a large improvement in quality of life compared with the control group (Cohen d=0.9). At the individual level, 32% (95% CI 22 to 40) of the STN group showed a substantial improvement in quality of life. 36% (95% CI 27 to 46) of the STN patients showed a profile of cognitive decline compared with the control group. Mood improved in 16 STN patients and declined in 16 subjects. Impaired attention, advanced age and a low l-dopa response at baseline predicted cognitive decline, whereas a high l-dopa response at baseline predicted an improvement in quality of life. Postoperative decrease in dopaminergic medication was not related to cognitive decline. CONCLUSIONS:STN DBS improves quality of life. However, a profile of cognitive decline can be found in a significant number of patients. l-dopa response, age and attention at baseline are predictors of cognitive and psychosocial outcome. 10.1136/jnnp.2007.140012
    Cognitive and Psychiatric Effects of STN versus GPi Deep Brain Stimulation in Parkinson's Disease: A Meta-Analysis of Randomized Controlled Trials. Wang Jia-Wei,Zhang Yu-Qing,Zhang Xiao-Hua,Wang Yun-Peng,Li Ji-Ping,Li Yong-Jie PloS one BACKGROUND:Deep brain stimulation (DBS) of either the subthalamic nucleus (STN) or the globus pallidus interna (GPi) can reduce motor symptoms in patients with Parkinson's disease (PD) and improve their quality of life. However, the effects of STN DBS and GPi DBS on cognitive functions and their psychiatric effects remain controversial. The present meta-analysis was therefore performed to clarify these issues. METHODS:We searched the PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials databases. Other sources, including internet-based clinical trial registries and grey literature sources, were also searched. After searching the literature, two investigators independently performed literature screens to assess the quality of the included trials and to extract the data. The outcomes included the effects of STN DBS and GPi DBS on multiple cognitive domains, depression, anxiety, and quality of life. RESULTS:Seven articles related to four randomized controlled trials that included 521 participants were incorporated into the present meta-analysis. Compared with GPi DBS, STN DBS was associated with declines in selected cognitive domains after surgery, including attention, working memory and processing speed, phonemic fluency, learning and memory, and global cognition. However, there were no significant differences in terms of quality of life or psychiatric effects, such as depression and anxiety, between the two groups. CONCLUSIONS:A selective decline in frontal-subcortical cognitive functions is observed after STN DBS in comparison with GPi DBS, which should not be ignored in the target selection for DBS treatment in PD patients. In addition, compared to GPi DBS, STN DBS does not affect depression, anxiety, and quality of life. 10.1371/journal.pone.0156721