Subthalamic Area Research Articles

Parkinson subtype-specific Granger-causal coupling and coherence frequency in the subthalamic area

Previous work on Parkinson’s disease (PD) has indicated a predominantly afferent coupling between affected arm muscle activity and electrophysiological activity within the subthalamic nucleus (STN). So far, no information is available indicating which frequency components drive the afferent information flow in PD patients. Non-directional coupling e.g. by measuring coherence is primarily established in the beta band as well as at tremor frequency. Based on previous evidence it is likely that different subtypes of the disease are associated with different connectivity patterns. Therefore, we determined coherence and causality between local field potentials (LFPs) in the STN and surface electromyograms (EMGs) from the contralateral arm in 18 akinetic-rigid (AR) PD patients and 8 tremor-dominant (TD) PD patients. During the intraoperative recording, patients were asked to lift their forearm contralateral to the recording side. Significantly more afferent connections were detected for the TD patients for tremor-periods and non-tremor-periods combined as well as for only tremor periods. Within the STN 74% and 63% of the afferent connections are associated with coherence from 4–8Hz and 8–12Hz, respectively. However, when considering only tremor-periods significantly more afferent than efferent connections were associated with coherence from 12 to 20Hz across all recording heights. No difference between efferent and afferent connections is seen in the frequency range from 4 to 12Hz for all recording heights. For the AR patients, no significant difference in afferent and efferent connections within the STN was found for the different frequency bands. Still, for the AR patients dorsal of the STN significantly more afferent than efferent connections were associated with coherence in the frequency range from 12 to 16Hz. These results provide further evidence for the differential pathological oscillations and pathways present in AR and TD Parkinson patients.

STN-DBS Reduces Saccadic Hypometria but Not Visuospatial Bias in Parkinson's Disease Patients.

In contrast to its well-established role in alleviating skeleto-motor symptoms in Parkinson's disease, little is known about the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on oculomotor control and attention. Eye-tracking data of 17 patients with left-hemibody symptom onset was compared with 17 age-matched control subjects. Free-viewing of natural images was assessed without stimulation as baseline and during bilateral DBS. To examine the involvement of ventral STN territories in oculomotion and spatial attention, we employed unilateral stimulation via the left and right ventralmost contacts respectively. When DBS was off, patients showed shorter saccades and a rightward viewing bias compared with controls. Bilateral stimulation in therapeutic settings improved saccadic hypometria but not the visuospatial bias. At a group level, unilateral ventral stimulation yielded no consistent effects. However, the evaluation of electrode position within normalized MNI coordinate space revealed that the extent of early exploration bias correlated with the precise stimulation site within the left subthalamic area. These results suggest that oculomotor impairments “but not higher-level exploration patterns” are effectively ameliorable by DBS in therapeutic settings. Our findings highlight the relevance of the STN topography in selecting contacts for chronic stimulation especially upon appearance of visuospatial attention deficits.

Dystonic tics induced by deep brain stimulation of the posterior subthalamic area for essential tremor.

OBJECTIVE The posterior subthalamic area (PSA) is a promising target of deep brain stimulation (DBS) for medication-refractory essential tremor (ET). This case series describes a novel adverse effect manifesting as dystonic tics in patients with ET undergoing DBS of the PSA. METHODS Six patients with ET received electrode implants for DBS of the dorsal and caudal zona incerta subregions of the PSA. RESULTS Five of the 6 patients developed dystonic tics soon after clinical programming. These tics were of varying severity and required reduction of the electrical stimulation amplitude. This reduction resolved tic occurrence without significantly affecting ET control. Dystonic tics were not observed in 39 additional patients who underwent DBS of the same brain regions for controlling non-ET movement disorders. CONCLUSIONS The pathophysiology of tic disorders is poorly understood and may involve the basal ganglia and related cortico-striato-thalamo-cortical circuits. This series is the first report of DBS-induced tics after stimulation of any brain target. Although the PSA has not previously been implicated in tic pathophysiology, it may be a candidate region for future studies.

Deep Brain Stimulation Target Selection for Parkinson's Disease.

During the "DBS Canada Day" symposium held in Toronto July 4-5, 2014, the scientific committee invited experts to discuss three main questions on target selection for deep brain stimulation (DBS) of patients with Parkinson's disease (PD). First, is the subthalamic nucleus (STN) or the globus pallidus internus (GPi) the ideal target? In summary, both targets are equally effective in improving the motor symptoms of PD. STN allows a greater medications reduction, while GPi exerts a direct antidyskinetic effect. Second, are there further potential targets? Ventral intermediate nucleus DBS has significant long-term benefit for tremor control but insufficiently addresses other motor features of PD. DBS in the posterior subthalamic area also reduces tremor. The pedunculopontine nucleus remains an investigational target. Third, should DBS for PD be performed unilaterally, bilaterally or staged? Unilateral STN DBS can be proposed to asymmetric patients. There is no evidence that a staged bilateral approach reduces the incidence of DBS-related adverse events.

Anatomic characterization of prelemniscal radiations by probabilistic tractography: implications in Parkinson's disease.

To characterize the anatomical connectivity of the prelemniscal radiations (Raprl), a white matter region within the posterior subthalamic area (PSA) that is an effective neurosurgical target for treating motor symptoms of Parkinson's disease (PD). Diffusion-weighted images were acquired from twelve healthy subjects using a 3T scanner. Constrained spherical deconvolution, a method that allows the distinction of crossing fibers within a voxel, was used to compute track-density images with sufficient resolution to accurately delineate distinct PSA regions and probabilistic tractography of Raprl in both hemispheres. Raprl connectivity was reproducible across all subjects and showed fibers traversing through this region towards primary and supplementary motor cortices, the orbitofrontal cortex, ventrolateral thalamus, and the globus pallidus, cerebellum and dorsal brainstem. All brain regions reached by Raprl fibers are part of motor circuits involved in the pathophysiology of PD; while these fiber systems converge at the level of the PSA, they can be spatially segregated. Fibers of distinct and specific motor control networks are identified within Raprl. The description of this anatomical crossroad suggests that, in the future, tractography could allow deep brain stimulation or lesional therapies in white matter targets according to individual patient's symptoms.

Incisionless transcranial MR-guided focused ultrasound in essential tremor: cerebellothalamic tractotomy

BackgroundAlready in the late 1960s and early 1970s, targeting of the “posterior subthalamic area (PSA)” was explored by different functional neurosurgical groups applying the radiofrequency (RF) technique to treat patients suffering from essential tremor (ET). Recent advances in magnetic resonance (MR)-guided focused ultrasound (MRgFUS) technology offer the possibility to perform thermocoagulation of the cerebellothalamic fiber tract in the PSA without brain penetration, allowing a strong reduction of the procedure-related risks and increased accuracy. We describe here the first results of the MRgFUS cerebellothalamic tractotomy (CTT).MethodsTwenty-one consecutive patients suffering from chronic (mean disease duration 29.9 years), therapy-resistant ET were treated with MRgFUS CTT. Three patients received bilateral treatment with a 1-year interval. Primary relief assessment indicators were the Essential Tremor Rating Scale (Fahn, Tolosa, and Marin) (ETRS) taken at follow-up (3 months to 2 years) with accent on the hand function subscores (HF16 for treated hand and HF32 for both hands) and handwriting. The evolution of seven patients with HF32 above 28 points over 32 (group 1) differentiated itself from the others’ (group 2) and was analyzed separately. Global tremor relief estimations were provided by the patients. Lesion reconstruction and measurement of targeting accuracy were done on 2-day post-treatment MR pictures for each CTT lesion.ResultsThe mean ETRS score for all patients was 57.6 ± 13.2 at baseline and 25.8 ± 17.6 at 1 year (n = 10). The HF16 score reduction was 92 % in group 2 at 3 months and stayed stable at 1 year (90 %). Group 1 showed only an improvement of 41 % at 3 months and 40 % at 1 year. Nevertheless, two patients of group 1 treated bilaterally had an HF16 score reduction of 75 and 88 % for the dominant hand at 1 year after the second side. The mean patient estimation of global tremor relief after CTT was 92 % at 2 days and 77 % at 1-year follow-up.ConclusionsCTT with MRgFUS was shown to be an effective and safe approach for patients with therapy-refractory essential tremor, combining neurological function sparing with precise targeting and the possibility to treat patients bilaterally.

Non-Human Primate: An Essential Building Brick in the Discovery of the Subthalamic Deep Brain Stimulation Therapy.

Non-Human Primate: An Essential Building Brick in the Discovery of the Subthalamic Deep Brain Stimulation Therapy.

The Feasibility of Using Acoustic Markers of Speech for Optimizing Patient Outcomes during Randomized Amplitude Variation in Deep Brain Stimulation: A Proof of Principle Methods Study.

Deep brain stimulation (DBS) is an effective treatment for reducing symptoms of tremor. A common and typically subjectively determined adverse effect of DBS is dysarthria. Current assessment protocols are driven by the qualitative judgments of treating clinicians and lack the sensitivity and objectivity required to optimize patient outcomes where multiple stimulation parameters are trialed. To examine the effect of DBS on speech in patients receiving stimulation to the posterior sub-thalamic area (PSA) via randomized manipulation of amplitude parameters. Six patients diagnosed with tremor receiving treatment via DBS of the PSA were assessed in a double-blinded, within-subjects experimental protocol. Amplitude (i.e., voltage or current) was randomly adjusted across 10 settings, while speech samples (e.g., sustained vowel, counting to 10) were recorded to identify the patient-specific settings required for optimal therapeutic benefit (reduced tremor) with minimal adverse effects (altered speech). Speech production between stimulation parameters was quantified using acoustic analysis. Speech changed as a response to DBS but those changes were not uniform across patients nor were they generally in line with changes in amplitude with the exception of reduced vocal control and increased mean silence length in two patients. Speech outcomes did not correlate with changes in tremor. Intra-individual changes in speech were detected as a response to modified amplitude; however, no clear pattern was observed across patients as a group. The use of objective acoustic measures allows for quantification of speech changes during DBS optimization protocols, even when those changes are subtle and potentially difficult to detect perceptually.

V40. Deep brain recordings using an implanted pulse generator in Parkinson’s disease

Introduction Deep brain stimulation (DBS) in the subthalamic nucleus (STN) for Parkinson’s disease (PD) has been shown to be a safe and effective treatment. Recent studies suggest that oscillatory beta activity could be used as a biomarker in patients with PD for subthalamic closed-loop stimulation leading to improved clinical benefit and reduced energy consumption. The aim of the present study was to evaluate the feasibility of local field potential (LFP) recordings for closed-loop stimulation using a new generation of implantable stimulators that also can record LFPs. Materials and methods Eight patients with PD (2 female, mean age 66.1 ± [SEM] 1.5 years; disease duration 10.5 ± 1.4 years) who underwent bilateral implantation of DBS electrodes in the STN were included in the study. LFP recordings were conducted at rest ON and OFF subthalamic high frequency stimulation (140 Hz) via DBS electrodes using the new stimulator device (bipolar recordings from contact pair 0–2, monopolar stimulation at contact 1). FFT based power spectra were calculated ON and OFF DBS, normalized to total power and compared between conditions. Results We recorded subthalamic oscillatory activity from 15 out of 16 DBS electrodes using the stimulator’s sensing function. We found discrete peaks in the beta band in 12 out of 15 electrodes (mean peak frequency 17 Hz). A significant reduction in averaged beta band power (13–30 Hz) of 14% was found ON compared to OFF DBS condition ( p = 0.002). No difference was found in the alpha band (7–13 Hz; p > 0.05). Direct comparison of beta peak frequency aligned power spectra across the group revealed a significant DBS related beta power reduction in a frequency range from −1.4 Hz to +5.8 Hz ( p ⩽ 0.03, FWE corrected) surrounding the individual peaks. Discussion We demonstrate for the first time recordings of human deep brain activity from a new generation of fully implantable pulse generators with sensing function. Discrete peaks in beta activity were obtained from the subthalamic area from 12 out of 15 electrodes when patients were OFF medication, moreover the new device could identify a significant suppression of beta band activity during DBS. The present results give further evidence for beta band activity being a useful biomarker in PD patients that can be followed with implantable systems.

The influence of rate of stimulation and pulse duration on efficacy of deep brain stimulation for Essential Tremor

Deep brain stimulation (DBS) is used to alleviate tremor in patients diagnosed with Essential Tremor who do not respond to conventional treatments. To achieve optimal tremor suppression, a large stimulus parameter space needs to be explored. In practice, a default pulse duration and stimulation rate (generally 60 us and 130 Hz) are often chosen and current or voltage varied to determine a clinically effective setting. This study explored the effect of rate of stimulation in 5 patients with bilateral DBS stimulation to the posterior sub-thalamic area (PSA). Additionally, the effects of varying charge per pulse by varying pulse duration alone or by varying current/voltage alone were compared. In experiment 1, rate was varied using the values 20, 70, 100, 130, 150 and 210 Hz, keeping pulse duration (90 us) and current (1 patient) or voltage (4 patients) fixed. In experiment 2, rate was fixed at 130 Hz, and charge per phase was varied first by changing pulse duration between 60, 90, and 120 us, and secondly by altering current or voltage by the same ratios. Tremor severity was categorized by two experienced clinicians. Figure 1 shows the effect rate for each subject. A repeated measures ANOVA showed a significant effect of rate (p <0.001) with the 40 Hz rate producing worse tremor scores than all rates of 100 Hz and above. Two patients showed a U-shaped response with best tremor suppression between 100 and 130 Hz, whereas the remaining patients showed a trend for better tremor suppression as rate increased across the whole range. Paired t-tests showed no significant difference between changing charge per phase via pulse duration or current/voltage, although both these effects were small, leading to poor statistical power.

Chronic stress-like syndrome as a consequence of medial site subthalamic stimulation in Parkinson's disease

Considering the functional organization of the subthalamic nucleus (STN), we hypothesized that subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease might have a differential impact on the hypothalamic-pituitary-adrenal axis in relation to the position of active stimulating contact within the STN. In addition, we searched for any STN-DBS-related morning plasma cortisol changes in association with postoperative anxiety and weight gain. A plasma cortisol measurement was performed on the day of initiation of bilateral STN-DBS and repeated after 1 and 17 months in twenty patients with advanced Parkinson's disease. The body weight change and anxiety scores following the implantation were assessed as well. The electrode positions in the STN were determined on T1-weighted magnetic resonance images. After initiation of stimulation, cortisol levels significantly decreased and the cortisol changes after 1 and 17 months strongly correlated with the position of active contact in the subthalamic area. Patients with at least one contact located more medially in the STN experienced a significantly greater decrease of cortisol than those with one or both active contacts more laterally. Furthermore, the lower cortisol levels were strongly associated with higher trait anxiety and weight gain. These changes mimicked the effects of chronic stress and suggest the disturbing impact of STN-DBS on limbic and motivational systems.

Higher neuronal discharge rate in the motor area of the subthalamic nucleus of Parkinsonian patients.

In Parkinson's disease, pathological synchronous oscillations divide the subthalamic nucleus (STN) of patients into a dorsolateral oscillatory region and ventromedial nonoscillatory region. This bipartite division reflects the motor vs. the nonmotor (associative/limbic) subthalamic areas, respectively. However, significant topographic differences in the neuronal discharge rate between these two STN subregions in Parkinsonian patients is still controversial. In this study, 119 STN microelectrode trajectories (STN length > 2 mm, mean = 5.32 mm) with discernible oscillatory and nonoscillatory regions were carried on 60 patients undergoing deep brain stimulation surgery for Parkinson's disease. 2,137 and 2,152 multiunit stable signals were recorded (recording duration > 10 s, mean = 21.25 s) within the oscillatory and nonoscillatory STN regions, respectively. Spike detection and sorting were applied offline on every multiunit stable signal using an automatic method with systematic quantification of the isolation quality (range = 0-1) of the identified units. In all, 3,094 and 3,130 units were identified in the oscillatory and nonoscillatory regions, respectively. On average, the discharge rate of better-isolated neurons (isolation score > 0.70) was higher in the oscillatory region than the nonoscillatory region (44.55 ± 0.87 vs. 39.97 ± 0.77 spikes/s, N = 665 and 761, respectively). The discharge rate of the STN neurons was positively correlated to the strength of their own and their surrounding 13- to 30-Hz beta oscillatory activity. Therefore, in the Parkinsonian STN, beta oscillations and higher neuronal discharge rate are correlated and coexist in the motor area of the STN compared with its associative/limbic area.

Multitarget, dual-electrode deep brain stimulation of the thalamus and subthalamic area for treatment of Holmes' tremor

Holmes' tremor (HT) is generally considered to be a symptomatic tremor associated with lesions of the cerebellum, midbrain, or thalamus. Deep brain stimulation (DBS) therapy for essential tremor and parkinsonian tremor has proved quite successful. In contrast, surgical treatment outcomes for HT have often been disappointing. The use of 2 ipsilateral DBS electrodes implanted in parallel within the thalamus for severe essential tremor has been reported. Since dual-lead stimulation within a single target can cover a wider area than single-lead stimulation, it produces greater effects. On the other hand, DBS of the subthalamic area (SA) was recently reported to be effective for refractory tremor. The authors implanted 2 DBS electrodes (one at the nucleus ventralis oralis/nucleus ventralis intermedius and the other at the SA) in 4 patients with HT. For more than 2 years after implantation, each patient's tremor was evaluated using a tremor rating scale under the following 4 conditions of stimulation: "on" for both thalamus and SA DBS; "off" for both thalamus and SA DBS; "on" for thalamus and "off" for SA DBS; and "on" for SA and "off" for thalamus DBS. The tremor in all patients was improved for more than 2 years (mean 25.8 ± 3.5 months). Stimulation with 2 electrodes exerted greater effect on the tremor than did 1-electrode stimulation. Interestingly, in all patients progressive effects were observed, and in one patient treated with DBS for 1 year, tremor did not appear even while stimulation was temporarily switched off, suggesting irreversible improvement effects. The presence of both resting and intentional/action tremor implies combined destruction of the pallidothalamic and cerebellothalamic pathways in HT. A larger stimulation area may thus be required for HT patients. Multitarget, dual-lead stimulation permits coverage of the wide area needed to suppress the tremor without adverse effects of stimulation. Some reorganization of the neural network may be involved in the development of HT because the tremor appears several months after the primary insult. The mechanism underlying the absence of tremor while stimulation was temporarily off remains unclear, but the DBS may have normalized the abnormal neural network. The authors successfully treated patients with severe HT by using dual-electrode DBS over a long period. Such DBS may offer an effective and safe treatment modality for intractable HT.

Neuronal Activity in the Subthalamic Cerebrovasodilator Area under Partial-Gravity Conditions in Rats.

The reduced-gravity environment in space is known to cause an upward shift in body fluids and thus require cardiovascular adaptations in astronauts. In this study, we recorded in rats the neuronal activity in the subthalamic cerebrovasodilator area (SVA), a key area that controls cerebral blood flow (CBF), in response to partial gravity. “Partial gravity” is the term that defines the reduced-gravity levels between 1 g (the unit gravity acceleration on Earth) and 0 g (complete weightlessness in space). Neuronal activity was recorded telemetrically through chronically implanted microelectrodes in freely moving rats. Graded levels of partial gravity from 0.4 g to 0.01 g were generated by customized parabolic-flight maneuvers. Electrophysiological signals in each partial-gravity phase were compared to those of the preceding 1 g level-flight. As a result, SVA neuronal activity was significantly inhibited by the partial-gravity levels of 0.15 g and lower, but not by 0.2 g and higher. Gravity levels between 0.2–0.15 g could represent a critical threshold for the inhibition of neurons in the rat SVA. The lunar gravity (0.16 g) might thus trigger neurogenic mechanisms of CBF control. This is the first study to examine brain electrophysiology with partial gravity as an experimental parameter.

Mechanisms of deep brain stimulation for essential tremor

Although essential tremor is often thought of as benign, it can be disabling to the point of justifying invasive deep brain stimulation (DBS). However, the mechanisms by which thalamic and subthalamic stimulation suppress tremor are poorly understood. In this issue of Brain , Groppa et al. (2014) quantified the performance of seven patients with essential tremor in a reaching task to determine the DBS target structures associated with therapeutic reduction in tremor and with the side effect of stimulation-induced ataxia. The optimum site of stimulation was usually in the posterior subthalamic area, beneath the inferior border of the thalamic nucleus ventralis intermedius. Probabilistic diffusion tractography identified the dentatothalamic tract as the key therapeutic DBS target structure. Supratherapeutic stimulation of this site produced upper limb ataxia, despite continued suppression of tremor. The authors systematically varied stimulation pulse strength and duration to find that stimulation chronaxies of 27 and 52 µs were associated with tremor suppression and the induction of ataxia, respectively. Chronaxie is loosely defined as the minimum duration at which a current twice threshold (minimum current with indefinitely long pulse duration) elicits a response and provides a clue as to the properties of the axons recruited. They reasoned that two different populations of large myelinated nerve fibres were affected: (i) dentatothalamic axons for the therapeutic effect; and (ii) afferent or efferent axons of the red nucleus for the stimulation-induced ataxia. However, the involvement of rubral pathways could not be confirmed with diffusion tractography. This work is an important contribution to a growing literature addressing the mechanisms of DBS and the preferred site of DBS stimulation for essential tremor. Ventralis intermedius has historically been the preferred stereotactic target for thalamotomy and DBS in the treatment of essential tremor and other tremor disorders (Miocinovic et al. , 2013), but recent postoperative correlations …

Physiological and anatomical decomposition of subthalamic neurostimulation effects in essential tremor

Postural tremor is the leading symptom in essential tremor, but in some cases intention tremor and limb ataxia emerge and can become highly disabling features. Deep brain stimulation of the thalamus or subthalamic white matter improve tremor and ataxia; however, the underlying network mechanisms are enigmatic. To elucidate the mechanisms of deep brain stimulation in essential tremor, we pursued a multimodal approach combining kinematic measures of reach-to-grasp movements, clinical assessments, physiological measures of neuronal excitability and probabilistic tractography from diffusion tensor imaging. Seven patients with essential tremor (age 62.9 ± 10.3 years, two females) received thalamic deep brain stimulation and a clinical examination of severity of limb tremor and ataxia at off stimulation, using therapeutic and supratherapeutic stimulation parameters. A reach-to-grasp task based on acoustic cues was also performed. To examine the electrical properties of target structures, we determined the chronaxie of neural elements modulated. A control group of 13 healthy subjects (age 56 ± 7.6 years, five females) underwent whole-brain diffusion tensor imaging at 3 T. Probabilistic tractography was applied in healthy subjects from seeds in cerebellum and midbrain to reconstruct the connectivity pattern of the subthalamic area. The positions of stimulation electrodes in patients were transferred into probability maps and connectivity values were correlated to clinical outcome measures. Therapeutic stimulation improved ataxia and tremor mainly during the target period of the reaching paradigm (63% reduction compared with off stimulation). Notably the acceleration (29%) and deceleration periods (41%) were improved. By contrast, supratherapeutic stimulation worsened ataxia during the deceleration period with a 55% increase of spatial variability, while maintaining near complete suppression of tremor. Chronaxie measures were in the range of rapidly-conducting myelinated fibres with significantly different values for the anti-tremor effect of therapeutic stimulation (27 s) and the pro-ataxic effect of supratherapeutic stimulation (52 s). The degree of connectivity to the dentato-thalamic tract at the stimulating electrode correlated significantly with the reduction of tremor in the therapeutic condition. Our data suggest that stimulation induced tremor reduction and induction of ataxia by supratherapeutic stimulation are mediated by different fibre systems. Probalistic tractography identified the dentato-thalamic tract as a likely target of tremor suppression. Stimulation-induced ataxia may be caused by additional recruitment of adjacent fibre systems at higher amplitudes. Stimulation with short pulse duration may help to increase the therapeutic window and focus on the anti-tremor effect.

Deep brain stimulation for Parkinsonʼs disease and other movement disorders

Deep brain stimulation (DBS) is now widely used in the treatment of Parkinson's disease, tremor, and dystonia. This review examines recent developments in the application of DBS to the management of movement disorders. In Parkinson's disease, recent work has demonstrated that early DBS may have a significant benefit on quality of life and motor symptoms while permitting a decrease in levodopa equivalent dosage. Thalamic DBS continues to be a well established target for the treatment of tremor, although recent work suggests that alternative targets such as the posterior subthalamic area may be similarly efficacious. The treatment of primary dystonia with DBS has been established in multiple recent trials, demonstrating prolonged symptomatic benefit. DBS is now an established symptomatic treatment modality for Parkinson's disease and other movement disorders. Future work will undoubtedly involve establishing new indications and targets in the treatment of movement disorders with further refinements to existing technology. Ultimately, these methods combined with biologically based therapies may catalyze a shift from symptomatic treatment to actually modifying the natural history of neurodegenerative diseases such as Parkinson's disease.

Changes in spontaneous brain activity in early Parkinson's disease

Resting state brain activity can provide valuable insights into the pathophysiology of Parkinson's disease (PD). The purpose of the present study was (a) to investigate abnormal spontaneous neuronal activity in early PD patients using resting-state functional MRI (fMRI) with a regional homogeneity (ReHo) method and (b) to demonstrate the potential of using changes in abnormal spontaneous neuronal activity for monitoring the progression of PD during its early stages. Seventeen early PD patients were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr disability scale and the Mini-mental State Examination (MMSE) were compared with seventeen gender- and age-matched healthy controls. All subjects underwent MRI scans using a 1.5T General Electric Signa Excite II scanner. The MRI scan protocol included whole-brain volumetric imaging using a 3D inversion recovery prepared (IR-Prep) fast spoiled gradient-echo pulse sequence and 2D multi-slice (22 axial slices covering the whole brain) resting-state fMRI using an echo planar imaging (EPI) sequence. Images were analyzed in SPM5 together with a ReHo algorithm using the in-house software program REST. A corrected threshold of p<0.05 was determined by AlphaSim and used in statistical analysis. Compared with the healthy controls, the early PD group showed significantly increased ReHo in a number of brain regions, including the left cerebellum, left parietal lobe, right middle temporal lobe, right sub-thalamic nucleus areas, right superior frontal gyrus, middle frontal gyrus (MFG), right inferior parietal lobe (IPL), right precuneus lobe, left MFG and left IPL. Additionally, significantly reduced ReHo was also observed in the early PD patients in the following brain regions: the left putamen, left inferior frontal gyrus, right hippocampus, right anterior cingulum, and bilateral lingual gyrus. Moreover, in PD patients, ReHo in the left putamen was negatively correlated with the UPDRS scores (r=−0.69). These results indicate that the abnormal resting state spontaneous brain activity associated with patients with early PD can be revealed by Reho analysis.

Cognitive effects of deep brain stimulation for essential tremor: evaluation at 1 and 6 years

Only a few studies have explored cognitive changes with deep brain stimulation (DBS) in patients with essential tremor (ET). Furthermore, the cognitive effects after years of electrical stimulation are unknown. Assessing the impact of stereotactic electrode implantation and the actual electrical stimulation on cognition in patients with ET in the short and long term is of interest, because DBS is increasingly applied and can offer deeper insight into human brain functions. We examined nine ET patients before surgery (PRE-SURGERY), and 1 and 6 years thereafter with DBS switched on (DBS-ON) and off (DBS-OFF). Standardized neuropsychological tests and reaction time tests were applied. There were no differences in tasks of verbal fluency, memory, and executive and intellectual functions comparing PRE-SURGERY, DBS-ON, and DBS-OFF at 1 and 6 years post-surgery. Imaging data revealed that the dorsolateral prefrontal cortex and mamillo-thalamic tracts crucial for cognitive functioning were spared by electrode implantation. Additionally, with electrodes targeting the thalamus and adjacent subthalamic area, the actual electrical stimulation did not affect neuropsychological functioning. However, lesions caused by electrode implantation led to an increase in simple reaction time, while the actual electrical stimulation restored impaired reaction time. This is the second largest study of neuropsychological functioning in patients with ET treated with DBS, and the first covering a neuropsychological long-term follow-up over 6 years. Neither stereotactic surgery nor electrical stimulation affected higher cognitive processes. This study proposes that cerebello-thalamo-cortical pathways in humans are involved in tasks of simple reaction time.

Hemichorea caused by intracranial hemorrhage following contralateral herpes zoster ophthalmicus

A healthy, 66-year-old, right-handed man was admitted to our university hospital and diagnosed with herpes zoster ophthalmicus (HZO). After 4weeks, he complained of hemichorea on his left side. Brain MRI showed a focal hemorrhage in the right subthalamic area. No evidence of aneurysmal lesion or cerebral angiitis was observed on cerebral angiography.