Revisiting Forel Field Surgery.

BACKGROUND: Lesioning the Forel field or the subthalamic region is considered a possible treatment for tremoric patients with Parkinson disease, essential tremor, and other diseases. This surgical treatment was performed in the 1960s to 1970s and was an alternative to thalamotomy. Recently, there has been increasing interest in the reappraisal of stimulating and/or lesioning these targets, partly as a result of innovations in imaging and noninvasive ablative technologies, such as magnetic resonance-guided focused ultrasonography. OBJECTIVE: We wanted to perform a thorough review of the subthalamic region, both from an anatomic and a surgical standpoint, to offer a comprehensive and updated analysis of the techniques and results reported for patients with tremor treated with different techniques. METHODS: We performed a systematic review of the literature, gathering articles that included patients who underwent ablative or stimulation surgical techniques, targeting the pallidothalamic pathways (pallidothalamic tractotomy), cerebellothalamic pathway (cerebellothalamic tractotomy), or subthalamic area. RESULTS: Pallidothalamic tractotomy consists of a reduced area that includes pallidofugal pathways. It may be considered an interesting target, given the benefit/risk ratio and the clinical effect, which, compared with pallidotomy, involves a lower risk of injury or involvement of vital structures such as the internal capsule or optic tract. Cerebellothalamic tractotomy and/or posterior subthalamic area are other alternative targets to thalamic stimulation or ablative surgery. CONCLUSIONS: Based on the significant breakthrough that magnetic resonance-guided focused ultrasonography has meant in the neurosurgical world, some classic targets such as the pallidothalamic tract, Forel field, and posterior subthalamic area may be reconsidered as surgical alternatives for patients with movement disorders.

Somnolence Preceded the Development of a Subthalamic Lesion in Neuromyelitis Optica Spectrum Disorder.

A 67-year-old woman with neuromyelitis optica spectrum disorder (NMOSD) developed severe somnolence. Ten days after admission, fluid-attenuated inversion-recovery magnetic resonance imaging (MRI) revealed hyperintense areas around the bilateral hypothalamus, which were not present on MRI at admission. The orexin level, which is decreased in idiopathic narcolepsy, was slightly decreased in her cerebrospinal fluid. Immunosuppressive treatment and methylphenidate markedly improved her somnolence. This case shows that NMOSD in the acute phase can cause somnolence in a patient without apparent lesions in the hypothalamus.

Transient increased thalamic-sensory connectivity and decreased whole-brain dynamism in autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with social communication deficits and restricted/repetitive behaviors and is characterized by large-scale atypical subcortical-cortical connectivity, including impaired resting-state functional connectivity between thalamic and sensory regions. Previous studies have typically focused on the abnormal static connectivity in ASD and overlooked potential valuable dynamic patterns in brain connectivity. However, resting-state brain connectivity is indeed highly dynamic, and abnormalities in dynamic brain connectivity have been widely identified in psychiatric disorders. In this study, we investigated the dynamic functional network connectivity (dFNC) between 51 intrinsic connectivity networks in 170 individuals with ASD and 195 age-matched typically developing (TD) controls using independent component analysis and a sliding window approach. A hard clustering state analysis and a fuzzy meta-state analysis were conducted respectively, for the exploration of local and global aberrant dynamic connectivity patterns in ASD. We examined the group difference in dFNC between thalamic and sensory networks in each functional state and group differences in four high-dimensional dynamic measures. The results showed that compared with TD controls, individuals with ASD show an increase in transient connectivity between hypothalamus/subthalamus and some sensory networks (right postcentral gyrus, bi paracentral lobule, and lingual gyrus) in certain functional states, and diminished global meta-state dynamics of the whole-brain functional network. In addition, these atypical dynamic patterns are significantly associated with autistic symptoms indexed by the Autism Diagnostic Observation Schedule. These converging results support and extend previous observations regarding hyperconnectivity between thalamic and sensory regions and stable whole-brain functional configuration in ASD. Dynamic brain connectivity may serve as a potential biomarker of ASD and further investigation of these dynamic patterns might help to advance our understanding of behavioral differences in this complex neurodevelopmental disorder.

The different association of allocentric and egocentric neglect with dorsal and ventral pathways: A case report.

RATIONALE: Egocentric neglect is characterized by responses missing on the contralateral side with respect to the viewer, while allocentric neglect is characterized in responses missing on the contralateral side with respect to the object . However, little has been reported about the neural tracts associated with egocentric and allocentric neglect. We investigated which neural tracts were involved in two types of neglect (egocentric and allocentric) in a stroke patient who showed allocentric neglect by using the Apple Cancellation test, a specialized test to distinguish between egocentric and allocentric neglect. PATIENT CONCERNS: He showed good cognitive function but presented with severe neglect on the left side (A 42-year-old, right-handed male patient). He was unable to undergo even the pencil and paper test for evaluation of the severity of neglect. DIAGNOSES: He was diagnosed as spontaneous intracerebral hemorrhage at the right basal ganglia and underwent conservative management at the neurosurgery department of a university hospital. INTERVENTIONS: Two weeks after onset, he began rehabilitation at the rehabilitation department of the same university hospital. During a seven month rehabilitation, the patient showed significant improvement of his severe left neglect. OUTCOMES: We used the Apple Cancellation test to distinguish between egocentric and allocentric neglect; the results failed to reveal egocentric neglect, however, they did reveal severe allocentric neglect. In addition, on diffusion tensor tractography (DTT) at 2 weeks after onset, the right superior longitudinal fasciculus (SLF) showed partial injury and narrowing in the parietal lobe compared to that of the left SLF. In addition, the right inferior fronto-occipital fasciculus (IFOF) was not reconstructed. By contrast, on 7-month post-onset DTT, the right SLF revealed elongation and thickening in the parietal lobe that approached similarity to that for the left SLF. However, the right IFOF was still not reconstructed. LESSONS: The associations of egocentric neglect with the dorsal pathway (SLF) and the association of allocentric neglect with the ventral pathway (IFOF) in the right hemisphere were demonstrated in a stroke patient. It appears that DTT can be helpful in demonstrating both the affected pathway and the neglect type in patients with neglect.

Long-Term Results of Deep Brain Stimulation of the Mamillotegmental Fasciculus in Chronic Cluster Headache.

BACKGROUND: Deep brain stimulation (DBS) and the proper target for chronic cluster headache (CCH) are still subjects of controversy. OBJECTIVES: We present our long-term results of analysis of the target and its structural connectivity. METHODS: Fifteen patients with drug-resistant CCH underwent DBS in coordinates 4 mm lateral to the III ventricular wall and 2 mm behind and 5 mm below the intercommissural point. The clinical parameters recorded were the number of weekly attacks, pain intensity, and duration of the headache. Structural connectivity was studied using 3-T MR diffusion tensor imaging (DTI). RESULTS: All of our patients improved from a mean of 39 attacks/week to 2; pain intensity decreased from 9 to 3 out of 10, and the mean cephalalgia duration decreased from 53 to 8 min. The mean stereotactic coordinates of the effective contact location were 6.1 mm lateral to the midcommissural point and 1.2 mm behind and 4.0 mm below the intercommissural point. DTI analysis showed that this target was connected to tracts and nuclei of the posterior mesencephalic tegmentum, specifically the dorsal longitudinal and mamillotegmental fasciculi. CONCLUSIONS: Our data showed DBS to be a safe and useful procedure for the treatment of drug-resistant CCH; the rate of improvement was higher than those found in other series. Although these are promising results, larger series targeting those fasciculi with a longer follow-up are needed.

Less is more - Pulse width dependent therapeutic window in deep brain stimulation for essential tremor.

BACKGROUND: Shorter pulse widths than conventional pulse width settings may lead to reduction of side effects and therefore be a valuable therapeutic option for deep brain stimulation (DBS) in patients with essential tremor (ET). OBJECTIVE: To compare the DBS effect of shorter pulse width at 40 µs (DBS-40 µs) to conventional pulse width at 60 µs (DBS-60 µs) on the therapeutic window in ET patients. METHODS: For this prospective, randomized, double-blind, crossover study 9 ET patients with chronic DBS of the ventral intermediate nucleus (VIM)/posterior subthalamic area (PSA) were recruited. Therapeutic window was calculated by determining efficacy and side effect thresholds for DBS-40 µs and DBS-60 µs. Tremor Rating Scales and Kinesia tremor analyses were used to compare clinical efficacy between the considered settings and deactivated DBS (DBS-OFF). Volume of neural activation (VNA) was calculated for both efficacy and side effect thresholds at each pulse width. RESULTS: DBS-40 µs showed a significantly larger therapeutic window than DBS-60 µs mainly due to higher side-effect thresholds. Both conditions significantly improved tremor compared to DBS-OFF, while efficacy was comparable between DBS-40 µs and DBS-60 µs. Moreover, VNA at efficacy threshold was smaller and less energy was required for tremor suppression with DBS-40 µs compared to DBS-60 µs. CONCLUSIONS: VIM/PSA-DBS with short pulse width represents a promising programming option for DBS in ET as it reduces side effects while maintaining efficient tremor suppression. Furthermore, our data support the notion of pulse width dependent selective modulation of distinct fiber tracts leading to widening of the therapeutic window.

Neuropsychological performance changes following subthalamic versus pallidal deep brain stimulation in Parkinson's disease: a systematic review and metaanalysis.

BACKGROUND: Studies comparing subthalamus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for the management of Parkinson's disease in terms of neuropsychological performance are scarce and heterogeneous. Therefore, we performed a systematic review and metaanalysis to compare neuropsychological outcomes following STN DBS versus GPi DBS. METHODS: A computer literature search of PubMed, the Web of Science, and Cochrane Central was conducted. Records were screened for eligible studies, and data were extracted and synthesized using Review Manager (v. 5.3 for Windows). RESULTS: Seven studies were included in the qualitative synthesis. Of them, four randomized controlled trials (n=345 patients) were pooled in the metaanalysis models. The standardized mean difference (SMD) of change in the Stroop color-naming test favored the GPi DBS group (SMD=-0.31, p=0.009). However, other neuropsychological outcomes did not favor either of the two groups (Stroop word-reading: SMD=-0.21, p=0.08; the Wechsler Adult Intelligence Scale (WAIS) digits forward: SMD=0.08, p=0.47; Trail Making Test Part A: SMD=-0.05, p=0.65; WAIS-R digit symbol: SMD=-0.16, p=0.29; Trail Making Test Part B: SMD=-0.14, p=0.23; Stroop color-word interference: SMD=-0.16, p=0.18; phonemic verbal fluency: bilateral DBS SMD=-0.04, p=0.73, and unilateral DBS SMD=-0.05, p=0.83; semantic verbal fluency: bilateral DBS SMD=-0.09, p=0.37, and unilateral DBS SMD=-0.29, p=0.22; Boston Naming Test: SMD=-0.11, p=0.33; Beck Depression Inventory: bilateral DBS SMD=0.15, p=0.31, and unilateral DBS SMD=0.36, p=0.11). CONCLUSIONS: There was no statistically significant difference in most of the neuropsychological outcomes. The present evidence does not favor any of the targets in terms of neuropsychological performance.

Altered functional connectivity of the subthalamus and the bed nucleus of the stria terminalis in obsessive-compulsive disorder.

BACKGROUND: The assessment of inter-regional functional connectivity (FC) has allowed for the description of the putative mechanism of action of treatments such as deep brain stimulation (DBS) of the nucleus accumbens in patients with obsessive-compulsive disorder (OCD). Nevertheless, the possible FC alterations of other clinically-effective DBS targets have not been explored. Here we evaluated the FC patterns of the subthalamic nucleus (STN) and the bed nucleus of the stria terminalis (BNST) in patients with OCD, as well as their association with symptom severity. METHODS: Eighty-six patients with OCD and 104 healthy participants were recruited. A resting-state image was acquired for each participant and a seed-based analysis focused on our two regions of interest was performed using statistical parametric mapping software (SPM8). Between-group differences in FC patterns were assessed with two-sample t test models, while the association between symptom severity and FC patterns was assessed with multiple regression analyses. RESULTS: In comparison with controls, patients with OCD showed: (1) increased FC between the left STN and the right pre-motor cortex, (2) decreased FC between the right STN and the lenticular nuclei, and (3) increased FC between the left BNST and the right frontopolar cortex. Multiple regression analyses revealed a negative association between clinical severity and FC between the right STN and lenticular nucleus. CONCLUSIONS: This study provides a neurobiological framework to understand the mechanism of action of DBS on the STN and the BNST, which seems to involve brain circuits related with motor response inhibition and anxiety control, respectively.

Anxiety-related experience-dependent white matter structural differences in adolescence: A monozygotic twin difference approach.

Anxiety is linked to deficits in structural and functional connectivity between limbic structures and pre-frontal cortices. We employed a monozygotic (MZ) twin difference design to examine the relationship between structural characteristics of the uncinate fasciculus (UF) measured by Diffusion Tensor Imaging (DTI) and anxiety symptoms in a sample of N = 100 monozygotic (genetically identical), adolescent twins. The MZ difference design allowed us focus on environmental factors that vary within twin pairs while controlling for genetic and environmental factors shared by twin pairs. Twins aged 13-18 years reported on symptoms of generalized anxiety and social phobia prior to participating in a neuroimaging visit. Regions of interest from the JHU ICBM atlas, including uncinate fasciculus and sagittal stratum as a control tract, were registered to the study template. We incorporated multiple diffusion tensor measures to characterize the white matter differences. Within twin pairs, the more anxious twin exhibited decreased fractional anisotropy (t = -2.22, p = 0.032) and axial diffusivity (t = -2.38, p = 0.022) in the left UF compared to the less anxious twin, controlling for age and gender. This study demonstrated the feasibility and advantages of adopting the MZ twin design for DTI measures in neuroimaging research.

Antiarrhythmics cure brain arrhythmia: The imperativeness of subthalamic ERG K+ channels in parkinsonian discharges.

ERG K+ channels have long been known to play a crucial role in shaping cardiac action potentials and, thus, appropriate heart rhythms. The functional role of ERG channels in the central nervous system, however, remains elusive. We demonstrated that ERG channels exist in subthalamic neurons and have similar gating characteristics to those in the heart. ERG channels contribute crucially not only to the setting of membrane potential and, consequently, the firing modes, but also to the configuration of burst discharges and, consequently, the firing frequency and automaticity of the subthalamic neurons. Moreover, modulation of subthalamic discharges via ERG channels effectively modulates locomotor behaviors. ERG channel inhibitors ameliorate parkinsonian symptoms, whereas enhancers render normal animals hypokinetic. Thus, ERG K+ channels could be vital to the regulation of both cardiac and neuronal rhythms and may constitute an important pathophysiological basis and pharmacotherapeutic target for the growing list of neurological disorders related to "brain arrhythmias."

Optimizing Prelemniscal Radiations as a Target for Motor Symptoms in Parkinson's Disease Treatment.

OBJECTIVE: To better define prelemniscal radiations (Raprl) as a target for the control of tremor and rigidity in Parkinson's disease (PD). METHODS: A total of 36 deep brain stimulation (DBS) electrodes were stereotactically implanted in Raprl contralateral to the extremities to be treated. Effects on symptoms were evaluated using UPDRS-III before and after DBS, and significance was determined using the Wilcoxon test. The location of DBS contacts in cases with optimum versus suboptimum results was evaluated using Student's t test and percentage improvement correlated through a bivariable Pearson test. The power and percentage of spike components for microelectrode recordings were statistically compared between the target point and structures located above and below. RESULTS: Raprl-DBS improved tremor and rigidity (p < 0.01). The potency of microelectrode recordings indicated that the target was formed by fibers. There was no correlation between demographic characteristics and clinical outcome, and there were no significant differences in stereotactic placement between cases with optimum and suboptimum results. Tremor and rigidity were selectively improved in cases with suboptimum results. CONCLUSION: Raprl-DBS is an effective treatment for the motor symptoms of PD. Selective improvement of symptoms suggests that the target has different fiber components related to either tremor or rigidity, and variations in improvement between cases may derive from individual variations of the location of these fibers.

Modulation of the cerebello-thalamo-cortical network in thalamic deep brain stimulation for tremor: a diffusion tensor imaging study.

BACKGROUND: Deep brain stimulation alleviates tremor of various origins. Several regions like the ventralis intermediate nucleus of thalamus, the caudal zona incerta, and the posterior subthalamic region are generally targeted. Previous work with fiber tractography has shown the involvement of the cerebello-thalamo-cortical network in tremor control. OBJECTIVE: To report the results of a prospective trial in a group of patients with tremor who underwent post hoc tractographic analysis after treatment with traditional thalamic deep brain stimulation. METHODS: A total of 11 patients (aged 64 ± 17 years, 6 male) were enrolled (essential tremor [6], Parkinson tremor [3], and myoclonic tremor in myoclonus dystonia [2]). Patients received 1 (3 patients), 2 (7 patients), or 3 (1 patient) quadripolar electrodes. A 32-direction diffusion tensor magnetic resonance imaging sequence was acquired preoperatively. Tractography was processed postoperatively for evaluation and the dentato-rubro-thalamic tract (DRT) was individually tracked. Electrode positions were determined with helical computed tomography. Electric fields (EFs) were simulated according to individual stimulation parameters in a standardized atlas brain space (ICBM-MNI 152). RESULTS: Tremor was reduced in all patients (69.4% mean) on the global (bilateral) tremor score. Effective contacts were located inside or in proximity to the DRT. In moderate tremor reduction (2 patients), the EFs were centered on its anterior border. In good and excellent tremor reduction (9 patients), EFs focused on its center. CONCLUSION: Deep brain stimulation of the cerebello-thalamo-cortical network reduces tremor. The DRT connects 3 traditional target regions for deep brain stimulation in tremor disease. Tractography techniques can be used to directly visualize the DRT and, therefore, optimize target definition in individual patients.

Individualized current-shaping reduces DBS-induced dysarthria in patients with essential tremor.

OBJECTIVE: To investigate in patients with essential tremor (ET) treated with thalamic/subthalamic deep brain stimulation (DBS) whether stimulation-induced dysarthria (SID) can be diminished by individualized current-shaping with interleaving stimulation (cs-ILS) while maintaining tremor suppression (TS). METHODS: Of 26 patients screened, 10 reported SID and were invited for testing. TS was assessed by the Tremor Rating Scale and kinematic analysis of postural and action tremor. SID was assessed by phonetic and logopedic means. Additionally, patients rated their dysarthria on a visual analog scale. RESULTS: In 6 of the 10 patients with ET, DBS-ON (relative to DBS-OFF) led to SID while tremor was successfully reduced. When comparing individualized cs-ILS with a non-current-shaped interleaving stimulation (ILS) in these patients, there was no difference in TS while 4 of the 6 patients showed subjective improvement of speech during cs-ILS. Phonetic analysis (ILS vs cs-ILS) revealed that during cs-ILS there was a reduction of voicing during the production of voiceless stop consonants and also a trend toward an improvement in oral diadochokinetic rate, reflecting less dysarthria. Logopedic rating showed a trend toward deterioration in the diadochokinesis task when comparing ON with OFF but no difference between ILS and cs-ILS. CONCLUSION: This is a proof-of-principle evaluation of current-shaping in patients with ET treated with thalamic/subthalamic DBS and experiencing SID. Data suggest a benefit on SID from individual shaping of current spread while TS is preserved. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with ET treated with DBS with SID, individualized cs-ILS reduces dysarthria while maintaining tremor control.

Possible mechanisms involved in subthalamotomy-induced dyskinesia in patients with Parkinson's disease.

BACKGROUND/AIMS: Operation-induced dyskinesia (OID) occurs in approximately 10% of patients submitted to subthalamotomy. The goal of the authors was to determine the possible causes of this feared complication. METHODS: The 54 patients who underwent unilateral subthalamotomy were divided into two groups: the OID group (OIDG), composed of 6 patients who developed dyskinesia following the operation, and the control group (CG), consisting of 48 patients who did not present this complication. The two groups were compared regarding age; sex; presence of levodopa-induced dyskinesia (LID) and/or stimulation-induced dyskinesia (SID); side of the operation; territories of the subthalamic nucleus (STN) involved by the lesion, and degree of lesion extension towards the zona incerta (ZI). RESULTS: The lesion involved the dorsolateral territory of the STN and was almost completely restricted to this nucleus in all patients of the OIDG, while it spread to the ZI in all but 1 patient of the CG. SID was significantly (p < 0.05) more frequent in the OIDG. There was also a strong trend favoring LID (p = 0.055). CONCLUSIONS: Damage to the dorsolateral territory of the STN and sparing of the ZI seem to be essential for the development of OID. SID and, to a lesser extent, LID are apparently significant risk factors for the development of this complication.

The impact of low-frequency stimulation of subthalamic region on self-generated isometric contraction in patients with Parkinson's disease.

Growing evidence suggests that spontaneous oscillatory low-frequency synchronization in the subthalamic nuclei (STN) may modulate motor performance in patients with Parkinson's disease (PD). To explore this in more detail, 15 PD patients chronically implanted with deep brain stimulation (DBS) electrodes in both STN were stimulated bilaterally at 5, 10, 20, 50 and 130 Hz and the effects of the DBS on self-initiated isometric elbow flexion (FLEX) and finger pinch (PINCH) were compared to performance without DBS. Baseline performance was very much impaired. Peak force was significantly greater during 130 and 10 Hz stimulation when compared to no stimulation in both tasks. Cumulative sums of the changes in mean rising force and peak force in the two tasks upon stimulation at 10 and 20 Hz demonstrated that patients improved their performance on stimulation, except for those with the best performance off stimulation who deteriorated with stimulation at 20 Hz. Thus, no effect was detected with 20 Hz stimulation at the group level. The current study highlights the need to consider the baseline performance of a subject in a given task when determining the effects of low-frequency STN stimulation in PD patients. It also demonstrates that stimulation at 10 Hz can improve motor function in subjects with poor baseline function.

The effects of bilateral stimulation of the subthalamic nucleus on heart rate variability in patients with Parkinson's disease.

The beneficial effects of subthalamic nucleus deep brain stimulation (STN-DBS) on motor symptoms and quality of life in Parkinson's disease (PD) are well known, but little is known of the effects on autonomic function. Diffusion of current during stimulation of the STN may simultaneously involve the motor and nonmotor, limbic and associative areas of the STN. The aims of this study were to examine whether STN stimulation affects functions of the autonomic nervous system and, if so, to correlate the effects with the active contacts of electrodes in the STN. Eight PD patients with good motor control and quality of sleep after STN-DBS surgery were recruited. All patients had two days of recordings with portable polysomnography (PSG) (first night with stimulation "on" and second night "off"). From the PSG data, the first sleep cycle of each recording night was defined. Heart rate variability (HRV) was analyzed between the same uninterrupted periods of the two sleep nights. In addition, the optimal electrode positions were defined from postoperative MRI studies, and the coordinates of active contacts were confirmed. HRV spectral analysis showed that only low-frequency (LF)/high-frequency (HF) power was significantly activated in the stimulation "on" groups (P = 0.011). There was a significant negative correlation between power change of LF/HF and electrode position lateral to the midcommissural point (ρ = 0.857, P = 0.007) These results demonstrate that STN-DBS can enhance sympathetic regulation; the autonomic response may be due to electrical signals being distributed to limbic components of the STN or descending sympathetic pathways in the zona incerta.

Expanded functional coupling of subcortical nuclei with the motor resting-state network in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortical connections, affecting functional integration within the motor network. Functional magnetic resonance imaging (fMRI) during motor tasks has revealed altered functional connectivity in MS, but it is unclear how much motor disability contributed to these abnormal functional interaction patterns. OBJECTIVE: To avoid any influence of impaired task performance, we examined disease-related changes in functional motor connectivity in MS at rest. METHODS: A total of 42 patients with MS and 30 matched controls underwent a 20-minute resting-state fMRI session at 3 Tesla. Independent component analysis was applied to the fMRI data to identify disease-related changes in motor resting-state connectivity. RESULTS: Patients with MS showed a spatial expansion of motor resting-state connectivity in deep subcortical nuclei but not at the cortical level. The anterior and middle parts of the putamen, adjacent globus pallidus, anterior and posterior thalamus and the subthalamic region showed stronger functional connectivity with the motor network in the MS group compared with controls. CONCLUSION: MS is characterised by more widespread motor connectivity in the basal ganglia while cortical motor resting-state connectivity is preserved. The expansion of subcortical motor resting-state connectivity in MS indicates less efficient funnelling of neural processing in the executive motor cortico-basal ganglia-thalamo-cortical loops.

Subthalamic local field potentials after seven-year deep brain stimulation in Parkinson's disease.

Studies describing subthalamic (STN) local field potentials (LFPs) recorded during deep brain stimulation (DBS) in patients with Parkinson's disease (PD), within the first month after DBS electrode implant, show that DBS modulates specific STN oscillations: whereas low-frequency (LF) oscillations (2-7 Hz) increase, beta oscillations (8-30 Hz) variably decrease. No data show whether LFPs remain stable for longer than one month after DBS surgery. Having long-term information is essential especially for use as a long-term feedback control signal for adaptive DBS systems. To evaluate how STN activity behaves years after prolonged chronic stimulation in PD we studied STN LFPs at rest without DBS and during ongoing DBS, in 11 parkinsonian patients 7 years (7.54±1.04) after STN electrode implantation for DBS (hyperchronic group) and in 16 patients 3 days after STN electrode implantation (acute group). STN LF and beta-band LFPs recorded at rest at 7 years contained almost the same information as those recorded at 3 days. STN recordings showed similar LFP responses to DBS in the acute and hyperchronic stages: whereas during ongoing DBS the LF power band increased for the whole population, beta activity decreased only in nuclei with significant beta activity at baseline. The LF/beta power ratio in all nuclei changed in both study groups, suggesting that this variable might be an even more informative marker of PD than the single LF and beta bands. Because STN LFP activity patterns and STN LFP responses to DBS stay almost unchanged for years after DBS electrode implantation they should provide a consistent feedback control signal for adaptive DBS.

Swallowing function in Parkinson's patients following Zona Incerta deep brain stimulation.

OBJECTIVE: The purpose of the present study was to examine whether there was a negative effect of caudal Zona Incerta deep brain stimulation (cZI DBS) on pharyngeal swallowing function in Parkinson's patients (PD). There are no former reports including swallowing and cZI DBS. METHODS: Eight patients (aged 49-71 years; median 62) were evaluated pre- and post-operatively, at 6 and 12 months after DBS surgery. Evaluation tools were fiberoptic endoscopic evaluation of swallowing examinations and patients' self-assessments of their swallowing function including a visual analog scale and quality-of-life-related questions. The swallowing protocol included Rosenbek's Penetration-Aspiration Scale, Secretion Severity Scale and parameters for preswallow spillage, pharyngeal residue, and pharyngeal clearance. RESULTS: There was no clear-cut effect of neurostimulation post-operatively at 6 and 12 months on any of the swallowing parameters except for the preswallow spillage that was slightly worsened in the stimulation on condition 12 months post-operatively. The answers to the self assessment questions did not vary significantly. CONCLUSIONS: The effect of the stimulation on the swallowing function varied among individuals, but the overall outcome was that cZI DBS did not seem to have a negative influence on swallowing function in the eight patients studied.

Antinociceptive effect of stimulating the zona incerta with glutamate in rats.

The zona incerta (ZI) is a subthalamic nucleus connected to several structures, some of them known to be involved with antinociception. The ZI itself may be involved with both antinociception and nociception. The antinociceptive effects of stimulating the ZI with glutamate using the rat tail-flick test and a rat model of incision pain were examined. The effects of intraperitoneal antagonists of acetylcholine, noradrenaline, serotonin, dopamine, or opioids on glutamate-induced antinociception from the ZI in the tail-flick test were also evaluated. The injection of glutamate (7 µg/0.25 µl) into the ZI increased tail-flick latency and inhibited post-incision pain, but did not change the animal performance in a Rota-rod test. The injection of glutamate into sites near the ZI was non effective. The glutamate-induced antinociception from the ZI did not occur in animals with bilateral lesion of the dorsolateral funiculus, or in rats treated intraperitoneally with naloxone (1 and 2 m/kg), methysergide (1 and 2 m/kg) or phenoxybenzamine (2 m/kg), but remained unchanged in rats treated with atropine, mecamylamine, or haloperidol (all given at doses of 1 and 2 m/kg). We conclude that the antinociceptive effect evoked from the ZI is not due to a reduced motor performance, is likely to result from the activation of a pain-inhibitory mechanism that descends to the spinal cord via the dorsolateral funiculus, and involves at least opioid, serotonergic and α-adrenergic mechanisms. This profile resembles the reported effects of these antagonists on the antinociception caused by stimulating the periaqueductal gray or the pedunculopontine tegmental nucleus.