M. Egidi

Movement-related modulation of neural activity in human basal ganglia and its L-DOPA dependency: recordings from deep brain stimulation electrodes in patients with Parkinson's disease.

Abstract. Through electrodes implanted for deep brain stimulation in three patients (5 sides) with Parkinsons disease, we recorded the electrical activity from the human basal ganglia before, during and after voluntary contralateral finger movements, before and after L-DOPA. We analysed the movement-related spectral changes in the electroencephalographic signal from the subthalamic nucleus (STN) and from the internal globus pallidus (GPi). Before, during and after voluntary movements, signals arising from the human basal ganglia contained two main frequencies: a high β (around 26 Hz), and a low β (around 18 Hz). The high β (around 26 Hz) power decreased in the STN and GPi, whereas the low β (around 18 Hz) power decrease was consistently found only in the GPi. Both frequencies changed their power with a specific temporal modulation related to the different movement phases. L-DOPA specifically and selectively influenced the spectral power changes in these two signal bands.

Dopamine‐dependent non‐linear correlation between subthalamic rhythms in Parkinson's disease

The basic information architecture in the basal ganglia circuit is under debate. Whereas anatomical studies quantify extensive convergence/divergence patterns in the circuit, suggesting an information sharing scheme, neurophysiological studies report an absence of linear correlation between single neurones in normal animals, suggesting a segregated parallel processing scheme. In 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated monkeys and in parkinsonian patients single neurones become linearly correlated, thus leading to a loss of segregation between neurones. Here we propose a possible integrative solution to this debate, by extending the concept of functional segregation from the cellular level to the network level. To this end, we recorded local field potentials (LFPs) from electrodes implanted for deep brain stimulation (DBS) in the subthalamic nucleus (STN) of parkinsonian patients. By applying bispectral analysis, we found that in the absence of dopamine stimulation STN LFP rhythms became non‐linearly correlated, thus leading to a loss of segregation between rhythms. Non‐linear correlation was particularly consistent between the low‐beta rhythm (13–20 Hz) and the high‐beta rhythm (20–35 Hz). Levodopa administration significantly decreased these non‐linear correlations, therefore increasing segregation between rhythms. These results suggest that the extensive convergence/divergence in the basal ganglia circuit is physiologically necessary to sustain LFP rhythms distributed in large ensembles of neurones, but is not sufficient to induce correlated firing between neurone pairs. Conversely, loss of dopamine generates pathological linear correlation between neurone pairs, alters the patterns within LFP rhythms, and induces non‐linear correlation between LFP rhythms operating at different frequencies. The pathophysiology of information processing in the human basal ganglia therefore involves not only activities of individual rhythms, but also interactions between rhythms.

Altered subthalamo-pallidal synchronisation in parkinsonian dyskinesias

The aim of this work was to study the role of subthalamo-pallidal synchronisation in the pathophysiology of dyskinesias. We recorded local field potentials (LFPs) in a patient with Parkinson’s disease and left surgery induced dyskinesias with double, bilateral deep brain stimulation electrode implants in the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Synchronisation was studied through coherence analysis. In the nuclei contralateral to the dyskinetic side of the body there was decreased STN-GPi coherence in the high beta range (20–30 Hz) and an enhanced coherence at low frequencies (<10 Hz). Despite the possible limitations arising from single-case observations, our findings suggest that parkinsonian dyskinesias are related to altered synchronisation between different structures of the basal ganglia. Firing abnormalities within individual basal ganglia nuclei are probably not enough to account for the complex balance between hypokinetic and hyperkinetic symptoms in human parkinsonian dyskinesias and altered interactions between nuclei should also be considered.

Anatomo-clinical correlation of intraoperative stimulation-induced side-effects during HF-DBS of the subthalamic nucleus

Abstract. The efficacy of deep brain stimulation of the subthalamic nucleus (STN) is dependent on the accuracy of targeting. In order to reduce the number of passes and, consequently, the duration of surgery and risk of bleeding, we have set up a new method based on direct magnetic resonance imaging (MRI) localisation of the STN. This procedure allows a short duration of the neurophysiological session (one or two initial tracks). Whenever a supplementary track is needed, the stimulation-induced side effects are analysed to choose from one of the remaining holes in Bens gun. A good knowledge of anatomical structures surrounding the STN is mandatory to relate side effects to the actual position of the track. In our series of 11 patients (22 sides, 37 tracks), the most common and reproducible side effects were those characterised by motor, sensorial, oculomotor and vegetative signs and symptoms. Moreover, the therapeutic window (distance between the current intensity needed to obtain the best clinical effect and the intensity capable to induce side effects) predicted clinical efficacy in the long-term, and contributed to the choice of which among the examined tracks had to be implanted with the chronic macroelectrode.

Impact of pyrexia on neurochemistry and cerebral oxygenation after acute brain injury.

Background: Postischaemic pyrexia exacerbates neuronal damage. Hyperthermia related cerebral changes have still not been well investigated in humans. Objective: To study how pyrexia affects neurochemistry and cerebral oxygenation after acute brain injury. Methods: 18 acutely brain injured patients were studied at the onset and resolution of febrile episodes (brain temperature ⩾38.7°C). Intracranial pressure (ICP), brain tissue oxygen tension (Pbro2), and brain tissue temperature (Tbr) were recorded continuously; jugular venous blood was sampled intermittently. Microdialysis probes were inserted in the cerebral cortex and in subcutaneous tissue. Glucose, lactate, pyruvate, and glutamate were measured hourly. The lactate to pyruvate ratio was calculated. Results: Mean (SD) Tbr rose from 38 (0.5) to 39.3 (0.3)°C. Arteriojugular oxygen content difference (AJDo2) fell from 4.2 (0.7) to 3.8 (0.5) vol% (p<0.05) and Pbro2 rose from 32 (21) to 37 (22) mm Hg (p<0.05). ICP increased slightly and no significant neurochemical alterations occurred. Opposite changes were recorded when brain temperature returned towards baseline. Conclusions: As long as substrate and oxygen delivery remain adequate, hyperthermia on its own does not seem to induce any further significant neurochemical alterations. Changes in cerebral blood volume may, however, affect intracranial pressure.

Gender differences in patients with Parkinson's disease treated with subthalamic deep brain stimulation

We investigated gender‐differences in clinical phenomenology and response to deep brain stimulation (DBS) of the subthalamic nucleus (STN) in a group of patients with advanced Parkinsons disease (PD). Thirty‐eight consecutive patients with PD (22 men and 16 women), bilaterally implanted for DBS of the STN, were evaluated 1 month before and 11 to 14 months after surgery. Gender differences in severity of the disease (HY and UPDRS), ability in the activities of daily living (ADL, UPDRS II), tremor and rigidity (UPDRS III), bradykinesia (UPDRS III and hand tapping test), levodopa‐induced dyskinesias (LIDs, UPDRS IV), and levodopa equivalent daily dosage (LEDD) were analyzed before and after intervention. We found a predominantly male population, with no gender‐related differences in age at onset, disease progression rate, or severity of disease. Nevertheless, women had more severe LIDs than men, only before the intervention. Bradykinesia was significantly less responsive to any kind of treatment (pharmacologic and neurosurgical) in women than in men. Finally, although STN‐DBS induced similar total benefits in both genders, postoperative assessment suggested that the ADL improved more in women than in men. Women and men with advanced PD appear to differ in some clinical features and in response to dopaminergic and STN‐DBS treatment.

Effects of hyperoxia on brain tissue oxygen tension in cerebral focal lesions

We evaluated the systemic and cerebral effects induced by an increase to 100% of the inspired oxygen fraction (FiO2) on 20 comatose patients with head injury (9 patients) and SAH (11 patients). Brain tissue oxygen tension (PtiO2) was measured through a Clark electrode inserted in penumbra-like areas. We performed 55 hyperoxia tests by increasing FiO2 from 35 +/- 8% to 100% in one second and calculating the PtiO2 index as: PtiO2 variation from baseline at 1 minute/arterial oxygen tension (PaO2) variation from baseline at 1 minute x 100. One hundred percent FiO2 caused an increase of both arterial (from 139 +/- 28 to 396 +/- 77 mmHg) and cerebral (from 22.6 +/- 14 to 65.4 +/- 60 mmHg) oxygenation after 1 minute. The range of the PtiO2 response was not uniform and two groups were identified. The change was small, 0.8 mmHg/min/100 mmHg PaO2 (+/- 0.7; range 0-2) when mean PtiO2 was 19.7 +/- 13.1 mmHg, while a stronger response, 8 mmHg/min/100 mmHg PaO2 (+/- 5; range 3-18) (p < 0.01) was found when mean PtiO2 was 31.7 +/- 14.3 mmHg. Since O2 diffusion should follow the gas diffusion law, the increase in diffusion distance due to a reduction of capillary density in focal lesions may explain this relationship.

Visualisation of the subthalamic nucleus: a multiple sequential image fusion (MuSIF) technique for direct stereotaxic localisation and postoperative control

Abstract. A novel multiple, sequential image fusion (MuSIF) procedure merging stereotaxic CT with frameless magnetic resonance imaging (MRI) is used since June 2000 to visualise and directly localise the subthalamic nucleus (STN) on T2 images. In 13 consecutive Parkinsons cases, intraoperative recording and stimulation verified bilateral electrode implantation guided by fused T2 images. In 85% of sides, final implantation opted for visualised target track. Implanted electrode position on postoperative T2 images matched planned target. Clinical follow-up reproduces literatures best results. This MuSIF technique, effective for direct STN targeting, has practical advantages: MRI can be performed regardless of surgery time; regular MR scanning to correct real image distortion is unneeded; and the need for multiple localising tracks is reduced by enabling us to account for each patients STN anatomy.

The subthalamic nucleus in Parkinson's disease: Power spectral density analysis of neural intraoperative signals

Abstract.To test a new tool for the neurophysiological identification of the human subthalamic nucleus (STN) during stereotactic surgery for the implantation of deep-brain-stimulation (DBS) electrodes, we analysed off-line the intraoperative signals recorded from patients with Parkinson’s disease. We estimated the power spectral density (PSD) along each penetration track (8 patients, 13 sides) and determined the spatial correlation of the PSD with the target location estimated from neuroimaging procedures (“anatomical target”), and with the final target location derived from standard intraoperative neurophysiological procedures for STN localization (“clinical target”). At each step we recorded the ‘on-line’ signal for 120 seconds; because the PSD was estimated by calculating the periodogram for 6-second epochs of neural signal, we had 20 epochs at each step. When the electrode track crossed the STN, the PSD in the 0.25-2.5 kHz band increased, peaking on average <0.5 mm cranial to the clinical target and 1.00±1.51 mm caudal to the anatomical target. When the track was outside the nucleus, the PSD remained unchanged. Even on recordings with low signal-tonoise ratio, off-line PSD analysis of neural signals showed a good correspondence with the target indicated by the surgical team. On-line intraoperative estimation of the PSD may be a simple, reliable, rapid and complementary approach to electrophysiological monitoring during STN surgery for Parkinson’s disease.

Gender-related differences in the human subthalamic area: a local field potential study.

The objective of this study was to investigate the possible existence of gender‐related neurophysiological differences in the oscillatory activity of the human subthalamic area. To this end, we recorded local field potentials (LFPs) after neurosurgical procedures for deep brain stimulation (DBS) in 24 patients (12 males and 12 females) with Parkinsons disease. LFP recordings at rest before levodopa medication (19 nuclei from 11 female patients and 16 nuclei from ten male patients) showed significantly higher power in the alpha/low‐beta band (8–12 Hz, P < 0.01; 13–20 Hz, P = 0.03) in females than in males. After levodopa medication (ten nuclei from six female patients and 11 nuclei from seven male patients), the power in the high‐gamma band (60–90 Hz) and of the 300 Hz rhythm was significantly higher in females than in males (high‐gamma, P = 0.007; 300 Hz, P = 0.002). These findings show that functional gender‐related differences in the central nervous system involve the human subthalamic area (STN) and its response to levodopa in Parkinsons disease. Gender‐related neurophysiological differences may be important for understanding gender‐specific features of neurodegenerative disorders and should be considered when interpreting LFP data from the human basal ganglia.