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Biomedical subjects

Jean A Saint-Cyr

Publications and source records attributed to Jean A Saint-Cyr.

16 recordsLinked to original sources

Subthalamic nucleus stimulation: improvements in outcome with reprogramming.

BACKGROUND: Deep brain stimulation (DBS) is currently the most effective surgical treatment for advanced Parkinson disease (PD). Even when the electrode is well positioned in the target, the optimization of clinical results depends on careful programming of electrical parameters and changes in antiparkinsonian drug dosages. OBJECTIVE: To determine whether stable outcomes from subthalamic nucleus DBS for PD can be improved by revising stimulation parameters and drug dosages through "hands-on" involvement of a neurologist expert in both movement disorders and DBS programming. METHODS: In 44 consecutive patients with PD with long-term stable response to subthalamic nucleus DBS (mean +/- SD, 3.5 +/- 1.7 years), we compared scores from the Unified Parkinson's Disease Rating Scale parts II through IV obtained immediately before and following a formal reprogramming of their stimulation. The reprogramming was performed by a neurologist expert in both PD and DBS and accompanied by further medication adjustments. The patients were subsequently followed up for as long as 14 months. RESULTS: In 24 patients (54.6%), the scores on the Unified Parkinson's Disease Rating Scale parts II and III significantly improved by 15.0% and 25.9%, respectively. Anti-PD drugs were significantly reduced (by 25.9%). No improvement was observed in 16 patients (36.4%), and the conditions of 4 patients (9.1%) worsened. CONCLUSIONS: Further improvement of parkinsonian signs can be achieved in the majority of patients even after long-term stable stimulation. Improved patient outcomes from subthalamic nucleus DBS are obtained when postoperative care is personally managed by a neurologist expert in movement disorders and DBS who is directly responsible for stimulation programming and simultaneous drug adjustments based on observed clinical responses to changing stimulation parameters.

Antiparkinson Agents↗

Speech and nonspeech sequence skill learning in adults who stutter.

UNLABELLED: Two studies compared the speech and nonspeech sequence skill learning of nine persons who stutter (PWS) and nine matched fluent speakers (PNS). Sequence skill learning was defined as a continuing process of stable improvement in speed and/or accuracy of sequencing performance over practice and was measured by comparing PWS's and PNS's performance curves of accuracy, reaction time, and sequence duration, as well as retention and transfer. In experiment one, participants completed a 30-trial finger tapping sequence and in experiment two, a 30-trial read-aloud sequence of nonsense syllables. Significant between-group differences were found in the speed of sequencing performance after practice, and on retention and transfer tests. These results partially supported the inference that PWS demonstrated differences in early stages of sequence skill learning compared to PNS. EDUCATIONAL OBJECTIVES: As a result of this activity the participant will be able to: (1) define skill learning and the important indicators of skill learning; (2) summarize the reviewed literature concerning the performance of PWS on speech and nonspeech sequencing tasks over practice; and (3) explain the implication of reaction time differences over practice between PWS and PNS.

Acoustic Stimulation↗

Exploring the recognition memory deficit in Parkinson's disease: estimates of recollection versus familiarity.

Current theories postulate that recognition memory can be supported by two independent processes: recollection (i.e. vivid memory for an item and the contextual details surrounding it) versus familiarity (i.e. the mere sense that an item is old). There is conflicting evidence on whether recognition memory is impaired in Parkinson's disease, perhaps because few studies have separated recollection from familiarity. We aimed to explore whether recollection or familiarity is more likely to be affected by Parkinson's disease, using three methods: (i) the word-frequency mirror effect to make inferences about recollection and familiarity based on recognition of high- versus low-frequency words, (ii) subjective estimates of recollection (remembering) versus familiarity (knowing), and (iii) a process-dissociation procedure where participants are required to endorse only some of the previously studied items on a recognition memory test, but not others. We tested Parkinson's disease patients (n = 19 and n = 16, age range = 58-77 years and age range = 50-75 in Experiments 1 and 2, respectively) and age- and education-matched controls (n = 23 and n = 16 in Experiments 1 and 2, respectively). Overall, the Parkinson's disease group showed a reduction in recognition memory, but this appeared to be primarily due to impairment of familiarity, with a lesser decline in recollection. We discuss how this pattern may be related to dysfunction of striatal, prefrontal and/or medial temporal regions in Parkinson's disease.

Aged↗

Correspondence of microelectrode mapping with magnetic resonance imaging for subthalamic nucleus procedures.

BACKGROUND: Magnetic resonance imaging (MRI) and microelectrode recording (MER) are commonly used to guide stereotactic procedures on the subthalamic nucleus (STN). Little is known about the correlation between the position of the STN as seen on MRI and that as determined by MER mapping. We compared these in 10 patients with Parkinson's disease. METHODS: The position of the STN was determined by intraoperative MER findings and stereotactic axial T2 magnetic resonance images with 2-mm slice thickness. Images were reconstructed in a 3-dimensional workstation. The anterior, posterior, medial, lateral, dorsal, and ventral borders of the STN defined with the MRI were measured relative to the midcommissural point. The location of STN activity during MER was reconstructed relative to the midcommissural point for comparison. RESULTS: Twenty-nine tracks recorded with microelectrodes provided clear spans of STN-like activity in 18 STN nuclei. The coordinates of MER were, in general, within the borders of the STN defined with the MRI. However, when analyzed individually, some of the tracks had STN-like activity outside the borders of the MRI-defined nucleus (mostly <1 mm). Three tracks had STN-like activity recorded between 2 and 3 mm more anterior than the anterior border of the nucleus defined with the MRI. CONCLUSIONS: There was a good correlation between MER and the borders of the STN defined in the MRI, except for the anterior-posterior axis, in which MER indicated that the STN extended more anteriorly than as suggested by MRI. This should be taken into account in STN surgery.

Action Potentials↗

Psychiatric symptoms following surgery for Parkinson's disease with an emphasis on subthalamic stimulation.

Bilateral subthalamic stimulation is a very effective neurosurgical treatment for advanced Parkinson's disease. Despite the range and frequency of psychiatric symptoms occurring in the postoperative state, most of these symptoms are transient and manageable. In clinical practice, preoperative psychiatric vulnerability, as with that of preoperative cognitive status, takes on an important role. Psychiatric assessment and active preoperative and postoperative intervention can potentially modify psychiatric outcomes. These psychiatric and psychological issues will take on greater importance, particularly with the rapid expansion of the number of neurosurgical sites and the need for adequate assessment and optimal management of patients. The paucity of the literature underscores the need for well-designed studies on psychiatric issues investigating both pathophysiology and clinical outcomes.

Anxiety↗

Involvement of human thalamus in the preparation of self-paced movement.

Cortical areas participating in the preparation of voluntary movements have been studied extensively. There is emerging evidence that subcortical structures, particularly the basal ganglia, also contribute to movement preparation. The thalamus is connected to both the basal ganglia and the cerebellar pathways, but its role in movement preparation has not been studied extensively in humans. We studied seven patients who underwent deep brain stimulation (DBS) electrode implantation in the thalamus for treatment of tremor (six patients) and myoclonus-dystonia (one patient). We recorded from the DBS contacts and scalp simultaneously, while patients performed self-paced wrist extension movements. Post-surgical MRI was used for precise localization of the DBS contacts in six patients. Back-averaging of the scalp recordings showed a slow negative movement-related potential (MRP) in all patients (onset 1846 +/- 189 ms prior to electromyography onset), whereas DBS electrode recordings showed pre-movement MRP in five out of seven patients. The thalamic MRP preceded both contralateral and ipsilateral wrist movements. There was no significant difference between the onset time of thalamic MRP (-2116 +/- 607 ms) and cortical MRP. Neither the scalp nor the thalamus showed pre-movement potentials with passive wrist extensions in two patients. In four patients with postoperative MRI who had thalamic MRP, the maximum amplitude or phase reversal occurred at contacts located in the ventral lateral nucleus. Frequency analysis was performed in the five patients with thalamic MRP. The medial frontocentral scalp contacts and the thalamic contacts with maximum MRP amplitude showed two discrete frequency bands in the alpha (mean peak 9 Hz) and beta (mean peak 17 Hz) range. Both frequency bands showed pre-movement event-related desynchronization (ERD). In the grand average, alpha and beta ERD in the scalp and beta ERD in the thalamus began 2.5-2.8 s prior to the onset of movement. However, the thalamic alpha ERD began considerably later, at 1.2 s before EMG onset. The beta band showed cortico-thalamic coherence from the beginning of the baseline period until approximately 0.5 s before the onset of movement. There was no cortico-thalamic coherence in the alpha band. Our findings suggest that the cerebellar thalamus is involved early in the process of movement preparation. Different cortico-subcortical circuits may mediate alpha and beta oscillations. During movement preparation, the motor thalamus and the supplementary motor area predominantly interact in the beta band.

Adult↗

Subthalamic nucleus deep brain stimulation for parkinson's disease after successful pallidotomy: clinical and electrophysiological observations.

Unilateral pallidotomy is an effective treatment for contralateral parkinsonism and dyskinesia, yet symptoms progress in many patients. Little is known about whether such patients obtain a useful response to subsequent bilateral subthalamic nucleus deep brain stimulation (STN DBS). Changes in Unified Parkinson's Disease Rating Scale (UPDRS) Motor and Activities of Daily Living (ADL) scores, medication requirements, and dyskinesias were measured. Clinical outcomes were compared to patients with de novo STN DBS. Neuronal recordings were performed. STN DBS resulted in a significant reduction in UPDRS Motor scores (42.1%; 95% confidence interval [CI], 26.9-57.4; P = 0.03), comparable with de novo STN DBS surgery (41%; 95% CI, 26-46%; P < 0.001). There was also less change in dyskinesia duration and disability scores (P = 0.017, 0.005). There were no side-to-side differences clinically or in the STN neuronal firing rates and patterns. Bilateral STN DBS is safe and efficacious in improving motor symptoms in patients with prior pallidotomy.

Activities of Daily Living↗

Determining the position and size of the subthalamic nucleus based on magnetic resonance imaging results in patients with advanced Parkinson disease.

OBJECT: The subthalamic nucleus (STN) is a target in surgery for Parkinson disease, but its location according to brain atlases compared with its position on an individual patient's magnetic resonance (MR) images is incompletely understood. In this study both the size and location of the STN based on MR images were compared with those on the Talairach and Tournoux, and Schaltenbrand and Wahren atlases. METHODS: The position of the STN relative to the midcommissural point was evaluated on 18 T2-weighted MR images (2-mm slices). Of 35 evaluable STNs, the most anterior, posterior, medial, and lateral borders were determined from axial images, dorsal and ventral borders from coronal images. These methods were validated using histological measurements in one case in which a postmortem examination was performed. The mean length of the anterior commissure-posterior commissure was 25.8 mm. Subthalamic nucleus borders derived from MR imaging were highly variable: anterior, 4.1 to -3.7 mm relative to the midcommissural point; posterior, 4.2 to 10 mm behind the midcommissural point; medial, 7.9 to 12.1 mm from the midline; lateral, 12.3 to 15.4 mm from the midline; dorsal, 0.2 to 4.2 mm below the intercommissural plane; and ventral, 5.7 to 9.9 mm below the intercommissural plane. The position of the anterior border on MR images was more posterior, and the medial border more lateral, than its position in the brain atlases. The STN was smaller on MR images compared with its size in atlases in the anteroposterior (mean 5.9 mm), mediolateral (3.7 mm), and dorsoventral (5 mm) dimensions. CONCLUSIONS: The size and position of the STN are highly variable, appearing to be smaller and situated more posterior and lateral on MR images than in atlases. Care must be taken in relying on coordinates relative to the commissures for targeting of the STN.

Adult↗

The subthalamic nucleus in the context of movement disorders.

The subthalamic nucleus (STN) has been regarded as an important modulator of basal ganglia output. It receives its major afferents from the cerebral cortex, thalamus, globus pallidus externus and brainstem, and projects mainly to both segments of the globus pallidus, substantia nigra, striatum and brainstem. The STN is essentially composed of projection glutamatergic neurons. Lesions of the STN induce choreiform abnormal movements and ballism on the contralateral side of the body. In animal models of Parkinson's disease this nucleus may be dysfunctional and neurons may fire in oscillatory patterns that can be closely related to tremor. Both STN lesions and high frequency stimulation ameliorate the major motor symptoms of parkinsonism in humans and animal models of Parkinson's disease and reverse certain electrophysiological and metabolic consequences of dopamine depletion. These new findings have led to a renewed interest in the STN. The aim of the present article is to review briefly the major anatomical, pharmacological and physiological aspects of the STN, as well as its involvement in the pathophysiology and treatment of Parkinson's disease.

Animals↗

Neuropsychology for movement disorders neurosurgery.

The neuropsychologist plays a crucial role in three phases of the neurosurgical treatment of movement disorder patients, namely screening, outcome evaluation and research. In screening patients, the differential diagnosis of dementia, impact of depression or other psychiatric conditions, and the influence of disease and medication-induced symptoms on cognitive performance must be determined. Postoperatively, systematic evaluations elucidate the cognitive costs or benefits of the procedure. The neuropsychologist is then able to provide feedback and counselling to the professional staff, patient and family to inform management strategies. Neuropsychologists also study alteration of cognitive processing due to lesions or stimulation, which, in tandem with functional imaging, shed light on plasticity in cortical and subcortical processing.

Dementia↗

Frontal-striatal circuit functions: context, sequence, and consequence.

The exact role of the basal ganglia in both the motor and non-motor domains has proven elusive since it is virtually impossible to refer to its function in isolation of cortical, and especially frontal cortical circuits. The result is that we often speak of frontal-striatal circuits and functions but this still leaves us in the dark when trying to specify basal ganglia information processing. A critical review of the data from both basic science and clinical studies suggests that we should break down processing along a temporal continuum, including the domains of context, sequential information processing, and feedback or reinforcement (i.e., the consequences of action). This analysis would cut across other theoretical constructs, such as attention, central executive, memory, and learning functions, traditionally employed in the neuropsychological literature. Under specified behavioral constraint, the basal ganglia can then be seen to be involved in fundamental aspects of attentional control (often covert), in the guidance of the early stages of learning (especially reinforcement-based, but also encoding strategies in explicit paradigms), and in the associative binding of reward to cue salience and response sequences via dopaminergic mechanisms. Parkinson's disease is considered to offer only a limited view of basal ganglia function due to partial striatal depletion of dopamine and the potential involvement of other structures and transmitters in its pathology. It is hoped that the present formulation will suggest new heuristic research strategies for basal ganglia research, permitting a closer link to be established between neurophysiological, functional imaging and neuropsychological paradigms.

Basal Ganglia↗

Long-term follow up of bilateral deep brain stimulation of the subthalamic nucleus in patients with advanced Parkinson disease.

OBJECT: The use of deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been associated with a marked initial improvement in individuals with advanced Parkinson disease (PD). Few data are available on the long-term outcomes of this procedure, however, or whether the initial benefits are sustained over time. The authors present the long-term results of a cohort of 25 individuals who underwent bilateral DBS of the STN between 1996 and 2001 and were followed up for 1 year or longer after implantation of the stimulator. METHODS: Patients were evaluated at baseline and repeatedly after surgery by using the Unified Parkinson's Disease Rating Scale (UPDRS); the scale was applied to patients during periods in which antiparkinsonian medications were effective and periods when their effects had worn off. Postoperative UPDRS total scores and subscores, dyskinesia scores, and drug dosages were compared with baseline values, and changes in the patients' postoperative scores were evaluated to assess the possibility that the effect of DBS diminished over time. In this cohort the median duration of follow-up review was 24 months (range 12-52 months). The combined (ADL and motor) total UPDRS score during the medication-off period improved after 1 year, decreasing by 42% relative to baseline (95% confidence interval [CI 35-50%], p < 0.001) and the motor score decreased by 48% (95% CI 42-55%, p < 0.001). These gains did diminish over time, although a sustained clinical benefit remained at the time of the last evaluation (41% improvement over baseline, 95% CI 31-50%; p < 0.001). Axial subscores at the time of the last evaluation showed only a trend toward improvement (p = 0.08), in contrast to scores for total tremor (p < 0.001), rigidity (p < 0.001), and bradykinesia (p = 0.003), for which highly significant differences from baseline were still present at the time of the last evaluation. Medication requirements diminished substantially, with total medication doses reduced by 38% (95% CI 27-48%, p < 0.001) at 1 year and 36% (95% CI 25-48%, p < 0.001) at the time of the last evaluation; this decrease may have accounted, at least in part, for the significant decrease of 46.4% (95% CI 20.2-72.5%, p = 0.007) in dyskinesia scores obtained by patients during the medication-on period. No preoperative demographic variable, such as the patient's age at the time of disease onset, age at surgery, sex, duration of disease before surgery, preoperative drug dosage, or preoperative severity of dyskinesia, was predictive of long-term outcome. The only predictor of a better outcome was the patient's preoperative response to levodopa. CONCLUSIONS: In this group of patients with advanced PD who underwent bilateral DBS of the STN, sustained improvement in motor function was present a mean of 2 years after the procedure, and sustained reductions in drug requirements were also achieved. Improvements in tremor, rigidity, and bradykinesia were more marked and better sustained over time than improvements in axial symptoms. A good preoperative response to levodopa predicted a good response to surgery.

Adult↗

Localization of clinically effective stimulating electrodes in the human subthalamic nucleus on magnetic resonance imaging.

OBJECT: The authors sought to determine the location of deep brain stimulation (DBS) electrodes that were most effective in treating Parkinson disease (PD). METHODS: Fifty-four DBS electrodes were localized in and adjacent to the subthalamic nucleus (STN) postoperatively by using magnetic resonance (MR) imaging in a series of 29 patients in whom electrodes were implanted for the treatment of medically refractory PD, and for whom quantitative clinical assessments were available both pre- and postoperatively. A novel MR imaging sequence was developed that optimized visualization of the STN. The coordinates of the tips of these electrodes were calculated three dimensionally and the results were normalized and corrected for individual differences by using intraoperative neurophysiological data (mean 5.13 mm caudal to the midcommissural point [MCP], 8.46 mm inferior to the anterior commissure-posterior commissure [AC-PC], and 10.2 mm lateral to the midline). Despite reported concerns about distortion on the MR image, reconstructions provided consistent data for the localization of electrodes. The neurosurgical procedures used, which were guided by combined neuroimaging and neurophysiological methods, resulted in the consistent placement of DBS electrodes in the subthalamus and mesencephalon such that the electrode contacts passed through the STN and dorsally adjacent fields of Forel (FF) and zona incerta (ZI). The mean location of the clinically effective contacts was in the anterodorsal STN (mean 1.62 mm posterior to the MCP, 2.47 mm inferior to the AC-PC, and 11.72 mm lateral to the midline). Clinically effective stimulation was most commonly directed at the anterodorsal STN, with the current spreading into the dorsally adjacent FF and ZI. CONCLUSIONS: The anatomical localization of clinically effective electrode contacts provided in this study yields useful information for the postoperative programming of DBS electrodes.

Adult↗

Movement-related neurons of the subthalamic nucleus in patients with Parkinson disease.

OBJECT: The subthalamic nucleus (STN) is a target in the surgical treatment of Parkinson disease (PD). Little is known about the neurons within the human STN that modulate movement. The authors' goal was to examine the distribution of movement-related neurons within the STN of humans by using microelectrode recording to identify neuronal receptive fields. METHODS: Data were retrospectively collected from microelectrode recordings that had been obtained in 38 patients with PD during surgery for placement of STN deep brain stimulation electrodes. The recordings had been obtained in awake, nonsedated patients. Antiparkinsonian medications were withheld the night before surgery. Neuronal discharges were amplified, filtered, and displayed on an oscilloscope and fed to an audio monitor. The receptive fields were identified by the presence of reproducible, audible changes in the firing rate that were time-locked to the movement of specific joint(s). The median number of electrode tracks per patient was six (range two-nine). The receptive fields were identified in 278 (55%) of 510 STN neurons studied. One hundred one tracks yielded receptive field data. Fourteen percent of 64 cells tested positive for face receptive fields, 32% of 687 cells tested positive for upper-extremity receptive fields, and 21% of 242 cells tested positive for lower-extremity receptive fields. Sixty-eight cells (24%) demonstrated multiple-joint receptive fields. Ninety-three cells (65%) with movement-related receptive fields were located in the dorsal half of the STN, and 96.8% of these were located in the rostral two thirds of the STN. Analysis of receptive field locations from pooled data and along individual electrode tracks failed to reveal a consistent somatotopic organization. CONCLUSIONS: Data from this study demonstrate a regional compartmentalization of neurons with movement-related receptive fields within the STN, supporting the existence of specific motor territories within the STN in patients suffering from PD.

Adult↗