The effect of deep brain stimulation on cognitive performance in patients with Parkinson’s disease

Introduction: There is a growing number of studies focusing on the short, medium and long term effects of deep brain stimulation (DBS) on motor and cognitive functions in Parkinson’s disease (PD). Substantially smaller number of studies performed on the results of surgical treatment of drugresistant tremor in patients with secondary Parkinson syndrome (PS). In our study we aimed to assess the effect of DBS on main cognitive functions, depression and anxiety in PD and PS patients. Methods: Ten PD patients with bilateral subthalamic-DBS and ten PS patients with bilateral thalamic Vim-DBS were evaluated before and after the surgery. Surgical planning was based on frameless MRI to CT image fusion with custom-developed Vister-3D planning software. The procedure was performed with guidance of RM and MHT stereotactic systems. Intraoperatively 3 to 5-channel microelectrode recording has been applied with registration of LeadToools (Medtronic) or Neurospot (Neurostar) recording equipment. Model 3389 electrodes were implanted bilaterally in all cases and connected to Activa PC or Kinetra dual channel implantable pulse generators. Results/Conclusion: The electrode position has been controlled with postoperative CT to preoperative MRI and to tractography co-registration. The patients’ cognitive performance level and clinical profile was compared not just to their own baseline, but also to a proper clinical control group, un-operated patients with PD and PS. The neuropsychological screening was focused on short term verbal and visuo-spatial memory, attention and executive functions. The possible relationships between area of stimulation, symptom severity and cognitive functioning will be discussed

Differential vulnerability of different forms of skill learning in Parkinson’s disease

The striatal dopaminergic dysfunction in Parkinson’s disease (PD) has been associated with deficits in skill learning in a number of studies, but the results are inconclusive so far. Motor sequence learning (especially sequence-specific learning) is found to be deficient in the majority of studies using the Serial Reaction Time Task (SRTT; Siegert, Taylor, Weatherall, & Abernethy, 2006; Jackson et al., 1995; Ferraro, Balota and Connor, 1993; Pascual-Leone et al., 1993, Muslimovic et al., 2007; Gobel et al., 2013; but see Kwak et al., 2012), although results are contradictory when verbal response is required instead of button presses (Westwater et al. 1998; Smith, Siegert and McDowall 2001). While problems with motor sequences seem to be prevalent, PD patients show intact performance on Artificial Grammar Learning (AGL) tasks, suggesting that the sequencing problem may be response type- or task type-dependent (Smith, Siegert and McDowall 2001; Witt, Nühsman and Deuschl, 2002) Acquisition of nonsequential probabilistic associations also seems to be vulnerable as evidenced by impaired PD performance on a probabilistic category learning task (Knowlton, Mangels et al., 1996; Shohamy, Myers, Onlaor, & Gluck, 2004). Our aim was to explore the nature of the skill learning deficit by testing different types of skill learning (sequential versus nonsequential, motor versus verbal) in the same group of Parkinson’s patients. 14 patients with PD (mean age: 59.77 range: 45.5-74) were compared to age-matched typical adults using 1) a Serial Reaction Time Task (SRTT) testing the learning of motor sequences, 2) an Artificial Grammar Learning (AGL) task testing the extraction of regularities from auditory sequences and 3) a Weather prediction task (PCL-WP), testing probabilistic category learning in a non-sequential task. In motor sequence learning on the SRTT task, the two groups did not differ in accuracy; PD patients were generally slower, and analysis of z-transformed reaction times showed no evidence of sequence learning in PD. A deficit in artificial grammar learning was present only as a tendency in the PD group. The PD group showed evidence of learning on the PCL task, and their learning performance was not statistically different from that of the control group. These results partly support and also extend previous findings suggesting that motor skill learning is vulnerable in PD, while other forms of skill learning are less prone to impairment. Results are also in line with previous assumptions that mechanisms underlying artificial grammar learning and probabilistic categorization do not depend on the striatum (Reber & Squire, 1999; Skosnik et al., 2002)

Differential vulnerability of different forms of skill learning in Parkinson’s disease Different forms of skill learning in Parkinson’s disease

The striatal dopaminergic dysfunction in Parkinson’s disease (PD) has been associated with deficits in skill learning, but results are inconclusive so far. Motor sequence learning (especially sequence-specific learning) is found to be deficient in the majority of studies using the SRT task (Jackson, Jackson, Harrison, Henderson, & Kennard, 1995; Siegert, Taylor, Weatherall, & Abernethy, 2006). While problems with motor sequences seem to be prevalent, PD patients show intact performance on AGL tasks, suggesting that the sequencing problem may be response- or taskdependent (Reber & Squire, 1999). Acquisition of nonsequential probabilistic associations also seems to be vulnerable as evidenced by impaired probabilistic category learning performance in PD (Knowlton, Mangels, & Squire, 1996; Shohamy, Myers, Onlaor, & Gluck, 2004). Our aim was to explore the nature of the skill learning deficit by testing different types of skill learning (sequential versus nonsequential, motor versus verbal) in the same group of Parkinson’s patients. 34 patients with PD (mean age: 62.59.77 years, SD: 7.67) were compared to age-matched typical adults using 1) a Serial Reaction Time Task (SRT) testing the learning of motor sequences, 2) an Artificial Grammar Learning (AGL) task testing the extraction of regularities from auditory sequences and 3) a Weather prediction task (PCL-WP), testing probabilistic category learning in a non-sequential task. In motor sequence learning (SRT task), the two groups did not differ in accuracy; PD patients were generally slower, and analysis of z-transformed reaction times also revealed deficient motor sequence learning in PD compared to the control group. The PD group showed no evidence of sequence learning. The PD group showed the same amount of learning on the PCL task as controls, and we observed higher rates of learning on the AGL task in PD patients than in controls. These results support and also extend previous findings suggesting that motor skill learning is vulnerable in PD, while other forms of skill learning are less prone to impairment. Results are also in line with previous assumptions that mechanisms underlying artificial grammar learning and probabilistic categorization do not depend on the striatum (Reber & Squire, 1999)

Application of fingertip support technique in microsurgery

ObjectiveThe physiological tremor which may extend up to 0.4–0.6 mm on the instrument tip in case of a well-skilled microsurgeon may cause diffi culties in any fi eld of microsurgery, in spite of using different armrests. The limit of correctness of medical robots is about 0.1 mm so far, but the application of these machines is expensive and not convenient for surgeons because the direct touch via microinstruments with living tissues is impossible.MethodThe effectiveness of the fi ngertip support technique has been proven by randomized analysis by exact measuring of the reduction of tremor.ResultsThe 0.1 mm precision could be reached by fi ngertip support. This extra precise work has not been available by hand so far.ConclusionThe signifi cant effect of fi ngertip support technique in neurosurgery has been certifi ed and published by exact measuring and clinical data.Our hypothesis could be the indication for trials in any microsurgical work. DOI: 10.17489/biohun/2010/1/0

The effect of subthalamic nucleus deep brain stimulation on executive and memory functions in Parkinson’s disease

Introduction: Although the improvement of motor symptoms in Parkinson’s disease after deep brain stimulation (DBS) of the subthalamic nucleus (STN) is well documented, there are open questions regarding its impact on cognitive functions (Fasano et al., 2012). The aim of the present study was to asses the effect of bilateral DBS of the STN on executive and memory functions in PD patients using an unstimulated PD control group matched on age, education, disease duration, motor symptoms, medication and DBS indication. Method: Thirteen PD patients with DBS implantation (DBS group) and 15 PD wait-listed patients (control group) participated in the study. A neuropsychological battery was used to assess cognitive functions, including general mental ability (Mini Mental State Examination), verbal (digit span) and spatial short-term memory (Corsi block-tapping task), working memory (n-back task), executive functions (phonemic and semantic verbal fluency, Stroop task, Trail Making B task), and event-based prospective memory (see Burgess et al., 2001). Each task was administered twice: before and after surgery in the DBS group with the stimulators on and with a similar time interval between the two task-administration points in the control group. Results: A series of mixed design ANOVAs was used with group (DBS vs. control group) as a between-subjects factor and assessment points (1st vs. 2nd) as a within-subjects factor. There was no significant difference between the DBS and the control groups’ performance in tasks measuring short-term verbal, spatial and working memory and executive functions assessed by the Trail Making B and the Stroop Tasks. The DBS group showed a significant decline on the semantic verbal fluency task after surgery compared to its own baseline level (p < .05). Additionally, the DBS group showed a decreased execution cost score at the second assessment point of the prospective memory task, compared to the control group (p < .05). Conclusion/Discussion: Our results provide support for the cognitive safety of the STN DBS using a wait-listed PD control group. The DBS group showed impaired performance after the surgery only on the semantic verbal fluency task which is in line with findings of previous studies. Furthermore, to the best of our knowledge, this is the first study to show that DBS of the STN boosts prospective memory, in particular intention execution functions. The findings will be discussed considering different possible effects of the STN DBS on frontosriatal networks

The effect of Parkinson’s disease and subthalamic deep brain stimulation on executive and memory functions.

Objectives: The aim of the present study was to asses the effect of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on executive and memory functions in PD patients using an unstimulated PD control group matched on motor symptoms, medication and DBS indication. Method: Thirteen PD patients with DBS implantation (DBS group) and 15 PD wait-listed patients (control group) participated in the study. A neuropsychological battery was used to assess cognitive functions. Each task was administered twice: before and after surgery in the DBS group with the stimulators on and with a similar time interval between the two taskadministration points in the control group. Results: There was no significant difference between the DBS and the control groups’ performance in tasks measuring short-term and working memory and main executive functions. The DBS group showed a significant decline on the semantic verbal fluency task after surgery compared to its own baseline level (p < .05). Additionally, the DBS group showed a decreased execution cost score at the second assessment point of the prospective memory task, compared to the control group (p < .05). Conclusions: Our results provide support for the cognitive safety of the STN DBS using a wait-listed PD control group. The DBS group showed impaired performance after the surgery only on the semantic verbal fluency task which is in line with findings of previous studies. Furthermore, to the best of our knowledge, this is the first study to show that DBS of the STN boosts prospective memory, in particular intention execution functions. Keywords: Parkinson disease, deep brain stimulation, executive functions, memor

Neuropsychological outcomes of subthalamic nucleus deep brain stimulation in Parkinson’s disease.

Despite the improvement of motor symptoms in Parkinson’s disease after deep brain stimulation (DBS) of the subthalamic nucleus (STN) is well documented, there are open questions regarding its impact on cognitive functions. The aim of the present study was to asses the effect of bilateral DBS of the STN on executive and memory functions in PD patients using an unstimulated PD control group matched on age, education, disease duration, motor symptoms, medication and DBS indication. All PD patients included in study fulfilled the UK Parkinson’s Disease Society Brain Bank clinical diagnostic criteria for PD. Thirteen PD patients with DBS implantation (DBS group) and 15 PD wait-listed patients (control group) participated in the study. Motor symptoms were assessed by the Unified Parkinson’s Rating Scale (UPDRS) motor score, anxiety by the State and Trait Anxiety Inventory (STAI) and depression by the Beck Depression Inventory (BDI). A neuropsychological battery was used to assess cognitive functions, including general mental ability (Mini Mental State Examination), verbal (digit span) and spatial short-term memory (Corsi block-tapping task), working memory (n-back task) and executive functions (phonemic and semantic verbal fluency, Stroop task, Trail Making B task). Each task was administered twice: before and after surgery in the DBS group with the stimulators on and with a similar time interval between the two task-administration points in the control group. There was no significant difference between the DBS and the control groups’ performance in tasks measuring short-term verbal, spatial and working memory and executive functions assessed by the Trail Making B and the Stroop Tasks. The DBS group showed a significant decline on the semantic verbal fluency task after surgery compared to its own baseline level (p < .05). The findings are discussed considering different possible effects of the STN DBS on frontosriatal networks. Keywords: Parkinson Disease, deep brain stimulation, executive function, memor

The effect of subthalamic nucleus deep brain stimulation on prospective memory functions in Parkinson’s disease

The aim of the study was to assess the effect of bilateral deep brain stimulation (DBS) of subthalamic nucleus (STN) on prospective memory (PM) functions involving thirteen PD patients with DBS implantation (DBS group) and 15 PD wait-listed patients (control group). Tasks of executive functions and an event-based PM task were applied. Each task was administered twice: before and after surgery in the DBS group with the stimulators on and with a similar time interval between the two task-administration points in the control group. The DBS group showed a significant decline on semantic verbal fluency task and a decreased execution cost score of the PM task after surgery, suggesting possible effects of STN DBS on PM-related frontosriatal networks

Target Identification for Stereotactic Thalamotomy Using Diffusion Tractography

BACKGROUND: Stereotactic targets for thalamotomy are usually derived from population-based coordinates. Individual anatomy is used only to scale the coordinates based on the location of some internal guide points. While on conventional MR imaging the thalamic nuclei are indistinguishable, recently it has become possible to identify individual thalamic nuclei using different connectivity profiles, as defined by MR diffusion tractography. METHODOLOGY AND PRINCIPAL FINDINGS: Here we investigated the inter-individual variation of the location of target nuclei for thalamotomy: the putative ventralis oralis posterior (Vop) and the ventral intermedius (Vim) nucleus as defined by probabilistic tractography. We showed that the mean inter-individual distance of the peak Vop location is 7.33 mm and 7.42 mm for Vim. The mean overlap between individual Vop nuclei was 40.2% and it was 31.8% for Vim nuclei. As a proof of concept, we also present a patient who underwent Vop thalamotomy for untreatable tremor caused by traumatic brain injury and another patient who underwent Vim thalamotomy for essential tremor. The probabilistic tractography indicated that the successful tremor control was achieved with lesions in the Vop and Vim respectively. CONCLUSIONS: Our data call attention to the need for a better appreciation of the individual anatomy when planning stereotactic functional neurosurgery