Subthalamic responses to motor cortex stimulation:Selective targeting of the subthalamic motor area

Introduction: Over the last decades, it has been shown consistently that deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates motor symptoms in Parkinson (PD) patients. However, in a substantial number of patients the beneficial effects of STN DBS are overshadowed by cognitive and/or limbic alterations. These side effects of STN DBS are thought to be caused by stimulation of the associative and limbic pathways that run through the STN. We hypothesize that an optimal effect of STN DBS on the motor symptoms without inducing cognitive and limbic side effects can be achieved by selective stimulation of the STN motor region by improved targeting. To achieve this goal, we made use of the cortico-subthalamic projection. We hypothesize that in PD patients motor cortex stimulation (MCS) evokes a specific response in the dorsolateral part of the STN, supposedly the STN motor area, that can be seen in both single unit activity and local field potentials (LFP). Material and Methods: Here we describe the results of one PD patient in which we performed MCS during the intra-operative STN microrecordings. In total, we measured single unit activity of eight neurons at various locations in the STN and LFP’s at the same locations. Data were analyzed using Matlab. All recordings were high pass filtered, the stimulus artifact was removed by time shifting, peristimulus time histograms were constructed from which significant excitatory and inhibitory responses were determined using the change point analysis. Results: The STN neurons had an average spontaneous firing rate of 64.6±36.3 Hz. Within the STN responses to MCS were seen, while outside the borders of the STN no responses were found. Responses differed between ventro-dorsal regions in the anterior-posterior and medio-lateral plane. In the anterior and lateral electrode at dorsal levels of the STN a significant early excitation (~10-50ms) and subsequent inhibition (50-110ms) were seen. The lateral electrode also showed a late excitation (~115-170ms). The responses we found were partially similar to reports in animal studies, but we did not observe the typical triphasic response. Conclusion: We found responses in the STN during MCS, which were significantly different in the dorsally recorded neurons in the lateral and anterior trajectory compared to the neurons recorded in other regions of the STN. In the near future MCS could be a novel tool to determine the motor area of the STN to optimize targeting for DBS in PD patients, thereby preventing cognitive and limbic side effect

Photomyogenic response in Niemann–Pick type C: a case report

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Increased EEG gamma band activity in Alzheimer’s disease and mild cognitive impairment

High frequency (30–70 Hz) gamma band oscillations in the human electro-encephalogram (EEG) are thought to reflect perceptual and cognitive processes. It is therefore interesting to study these measures in cognitive impairment and dementia. To evaluate gamma band oscillations as a diagnostic biomarker in Alzheimer’s disease (AD) and mild cognitive impairment (MCI), 15 psychoactive drug naïve AD patients, 20 MCI patients and 20 healthy controls participated in this study. Gamma band power (GBP) was measured in four conditions viz. resting state, music listening, story listening and visual stimulation. To evaluate test–retest reliability (TRR), subjects underwent a similar assessment one week after the first. The overall TRR was high. Elevated GBP was observed in AD when compared to MCI and control subjects in all conditions. The results suggest that elevated GBP is a reproducible and sensitive measure for cognitive dysfunction in AD in comparison with MCI and controls

Differential effects of subthalamic nucleus stimulation in advanced Parkinson disease on reaction time performance

The aim of the present study was to assess the effect of bilateral subthalamic nucleus (STN) stimulation and dopaminergic medication on speed of mental processing and motor function. Thirty-nine patients suffering from advanced Parkinson disease (PD) were operated on. Motor function and reaction time (RT) performance [simple RT (SRT) and complex RT (CRT)] were evaluated under four experimental conditions with stimulation (stim) and medication (med) on and off: stim-on/med-on, stim-on/med-off, stim-off/med-off and stim-off/med-on. In the last condition, the patients received either low medication (usual dose) or high medication (suprathreshold dose). STN stimulation improved the motor performance in the SRT and CRT tasks. Furthermore, STN deep brain stimulation (DBS) also improved response preparation as shown by the significant improvement of the RT performance in the SRT task. This effect of STN DBS on the RT performance in the SRT task was greater as compared with the CRT task. This is due to the more complex information processing that is required in the CRT task as compared to the SRT task. These data suggest that treatment of STN hyperactivity by DBS improves motor function, confirming earlier reports, but has a differential effect on cognitive functions. The STN seems to be an important modulator of cognitive processing and STN DBS can differentially affect motor and associative circuits

The association between surgical characteristics and cognitive decline following deep brain stimulation of the subthalamic nucleus in Parkinson's disease

Objective: Despite optimal improvement in motor functioning, both shortand long-term studies have reported small but consistent changes in cognitive functioning following STN-DBS in Parkinson's disease (PD). The aim of the present study was to explore whether surgical characteristics were associated with cognitive decline one year following STN-DBS.Methods: We retrospectively analyzed 49 PD patients who underwent bilateral STN-DBS. Cognitive change scores were related to the number of microelectrode recording (MER) trajectories, the STN length as measured by MER, and cortical entry points. Regression analyses were corrected for age at surgery, disease duration, education and preoperative levodopa responsiveness. Patients were then divided into a cognitive and non-cognitive decline group for each neuropsychological test and compared regarding demographic and surgical characteristics.Results: One year postoperatively, significant declines were found in verbal fluency, Stroop Color-Word test and Trail Making Test B (TMT-B). Only changes in TMT-B were associated with the coronal entry point in the right hemisphere. The number of MER trajectories and STN length were not associated with cognitive change scores. When comparing the cognitive decline and non-cognitive decline groups, no significant differences were found in surgical characteristics.Conclusions: The electrode passage through the right prefrontal lobe may contribute to subtle changes in executive function. However, only few patients showed clinically relevant cognitive decline. The use of multiple MER trajectories and a longer STN length were not associated with cognitive decline one year following surgery. From a cognitive point of view, DBS may be considered a relatively safe procedure

Optimal training dataset composition for SVM-based, age-independent, automated epileptic seizure detection

Automated seizure detection is a valuable asset to health professionals, which makes adequate treatment possible in order to minimize brain damage. Most research focuses on two separate aspects of automated seizure detection: EEG feature computation and classification methods. Little research has been published regarding optimal training dataset composition for patient-independent seizure detection. This paper evaluates the performance of classifiers trained on different datasets in order to determine the optimal dataset for use in classifier training for automated, age-independent, seizure detection. Three datasets are used to train a support vector machine (SVM) classifier: (1) EEG from neonatal patients, (2) EEG from adult patients and (3) EEG from both neonates and adults. To correct for baseline EEG feature differences among patients feature, normalization is essential. Usually dedicated detection systems are developed for either neonatal or adult patients. Normalization might allow for the development of a single seizure detection system for patients irrespective of their age. Two classifier versions are trained on all three datasets: one with feature normalization and one without. This gives us six different classifiers to evaluate using both the neonatal and adults test sets. As a performance measure, the area under the receiver operating characteristics curve (AUC) is used. With application of FBC, it resulted in performance values of 0.90 and 0.93 for neonatal and adult seizure detection, respectively. For neonatal seizure detection, the classifier trained on EEG from adult patients performed significantly worse compared to both the classifier trained on EEG data from neonatal patients and the classier trained on both neonatal and adult EEG data. For adult seizure detection, optimal performance was achieved by either the classifier trained on adult EEG data or the classifier trained on both neonatal and adult EEG data. Our results show that age-independent seizure detection is possible by training one classifier on EEG data from both neonatal and adult patients. Furthermore, our results indicate that for accurate age-independent seizure detection, it is important that EEG data from each age category are used for classifier training. This is particularly important for neonatal seizure detection. Our results underline the under-appreciated importance of training dataset composition with respect to accurate age-independent seizure detection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11517-016-1468-y) contains supplementary material, which is available to authorized users

The association between surgical characteristics and cognitive decline following deep brain stimulation of the subthalamic nucleus in Parkinson's disease

Objective: Despite optimal improvement in motor functioning, both shortand long-term studies have reported small but consistent changes in cognitive functioning following STN-DBS in Parkinson's disease (PD). The aim of the present study was to explore whether surgical characteristics were associated with cognitive decline one year following STN-DBS.Methods: We retrospectively analyzed 49 PD patients who underwent bilateral STN-DBS. Cognitive change scores were related to the number of microelectrode recording (MER) trajectories, the STN length as measured by MER, and cortical entry points. Regression analyses were corrected for age at surgery, disease duration, education and preoperative levodopa responsiveness. Patients were then divided into a cognitive and non-cognitive decline group for each neuropsychological test and compared regarding demographic and surgical characteristics.Results: One year postoperatively, significant declines were found in verbal fluency, Stroop Color-Word test and Trail Making Test B (TMT-B). Only changes in TMT-B were associated with the coronal entry point in the right hemisphere. The number of MER trajectories and STN length were not associated with cognitive change scores. When comparing the cognitive decline and non-cognitive decline groups, no significant differences were found in surgical characteristics.Conclusions: The electrode passage through the right prefrontal lobe may contribute to subtle changes in executive function. However, only few patients showed clinically relevant cognitive decline. The use of multiple MER trajectories and a longer STN length were not associated with cognitive decline one year following surgery. From a cognitive point of view, DBS may be considered a relatively safe procedure