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G Foffani

Publications and source records attributed to G Foffani.

13 recordsLinked to original sources

Low-frequency subthalamic oscillations increase after deep brain stimulation in Parkinson's disease.

This work is the second of a series of papers in which we investigated the neurophysiological basis of deep brain stimulation (DBS) clinical efficacy using post-operative local field potential (LFP) recordings from DBS electrodes implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease. We found that low-frequency (1-1.5Hz) oscillations in LFP recordings from the STN of patients with Parkinson's disease dramatically increase after DBS of the STN itself (log power change=0.93+/-0.62; Wilcoxon: p=0.0002, n=13), slowly decaying to baseline levels after turning DBS off. The DBS-induced increase of low-frequency LFP oscillations is highly reproducible and appears only after the delivery of DBS for a time long enough to induce clinical improvement. This increase of low-frequency LFP oscillations could reflect stimulation-induced modulation of network activity or could represent changes of the electrochemical properties at the brain-electrode interface.

Action Potentials↗

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.

Adult↗

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 Parkinson's 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 Parkinson's 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.

Action Potentials↗

Subthalamic oscillatory activities at beta or higher frequency do not change after high-frequency DBS in Parkinson's disease.

This study aimed to assess whether changes in the patterns of local field potential (LFP) oscillations of the subthalamic nucleus (STN) underlie to the clinical improvement within 60 s after turning off subthalamic DBS. We studied by spectral analysis the STN LFPs recorded in 13 nuclei from 7 patients with Parkinson's disease before and immediately after unilateral high-frequency (130 Hz) stimulation of the same nucleus, when the clinical benefit of DBS was unchanged. The results were compared with LFP data previously reported [A. Priori, G. Foffani, A. Pesenti, F. Tamma, A.M. Bianchi, M. Pellegrini et al., Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson's disease. Exp. Neurol. 189 (2004) 369-379]--namely 13 STN from 9 parkinsonian patients recorded before and after levodopa administration--which were used as a control. Before DBS, in the 'off' clinical state after overnight withdrawal of dopaminergic therapy, the STN spectrum did not significantly differ from the control nuclei, showing prominent activity at beta frequencies (13-20 and 20-35 Hz). After DBS (10-15 min) of the STN, the recorded nuclei significantly differed from the control, failing to show significant changes either in the beta bands or at higher frequencies (60-90 and 250-350 Hz). The patterns of subthalamic LFP oscillations after DBS therefore differ from those after dopaminergic medication. These results suggest (1) that subthalamic LFP modulations are not the epiphenomenon of peripheral motor improvement and (2) that the transitory clinical efficacy maintained after discontinuation of subthalamic DBS is not associated with local modulation of LFP activity at beta or higher frequencies within the STN.

Action Potentials↗

Movement-related frequency modulation of beta oscillatory activity in the human subthalamic nucleus.

Event-related changes of brain electrical rhythms are typically analysed as amplitude modulations of local field potential (LFP) oscillations, like radio amplitude modulation broadcasting. In telecommunications, frequency modulation (FM) is less susceptible to interference than amplitude modulation (AM) and is therefore preferred for high-fidelity transmissions. Here we hypothesized that LFP rhythms detected from deep brain stimulation (DBS) electrodes implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease could represent movement-related activity not only in AM but also in FM. By combining adaptive autoregressive identification with spectral power decomposition, we were able to show that FM of low-beta (13-20 Hz) and high-beta (20-35 Hz) rhythms significantly contributes to the involvement of the human STN in movement preparation, execution and recovery, and that the FM patterns are regulated by the dopamine levels in the system. Movement-related FM of beta oscillatory activity in the human subthalamic nucleus therefore provides a novel informational domain for rhythm-based pathophysiological models of cortico-basal ganglia processing.

Adult↗

Physiological recordings from electrodes implanted in the basal ganglia for deep brain stimulation in Parkinson's disease. the relevance of fast subthalamic rhythms.

Deep brain stimulation electrodes implanted in the subthalamic nucleus of patients with Parkinson's disease allow electrophysiological recordings from the human basal ganglia. Subthalamic local field potential recordings revealed the presence of multiple rhythms, from the classical EEG frequency range (<50 Hz), to surprisingly high frequencies (70 Hz and 300 Hz). Fast rhythms are particularly attractive because of their likely interaction with the excitatory mechanisms of action of deep brain stimulation. Here we investigated whether the two rhythms at 70 Hz and at 300 Hz represent distinct modes of operation, and therefore different targets, within the subthalamic nucleus. We retrospectively analyzed the dataset we used to describe the 300 Hz rhythm (Foffani, Priori et al., Brain 126: 2153-2163, 2003) searching for significant 70 Hz oscillations after levodopa administration. Whereas (as previously reported) 300 Hz activity was a consistent feature in the dataset, significant 70 Hz activity was observed in only 2 of 11 nuclei. Therefore, 70 Hz oscillations are not a necessary condition for the presence of 300 Hz oscillations. The two rhythms probably arise from different mechanisms, reflecting different functional and/or spatial aspects of subthalamic pathophysiology. Fast subthalamic oscillations could be exploited for intra-operative electrophysiological monitoring of the subthalamic nucleus, post-operative confirmation of electrode placement and patient-specific 'reglage' of the electrical parameters for chronic deep brain stimulation.

Basal Ganglia↗

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.

Deep Brain Stimulation↗

Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson's disease.

The subthalamic nucleus (STN) has a key role in the pathophysiology of Parkinson's disease and is the primary target for high-frequency deep brain stimulation (DBS). The STN rest electrical activity in Parkinson's disease, however, is still unclear. Here we tested the hypothesis that pharmacological modulation of STN activity has rhythm-specific effects in the classical range of EEG frequencies, below 50 Hz. We recorded local field potentials (LFPs) through electrodes implanted in the STN of patients with Parkinson's disease (20 nuclei from 13 patients). After overnight withdrawal of antiparkinsonian therapy, LFPs were recorded at rest both before (off) and after (on) acute administration of different antiparkinsonian drugs: levodopa, apomorphine, or orphenadrine. In the off-state, STN LFPs showed clearly defined peaks of oscillatory activity below 50 Hz: at low frequencies (2-7 Hz), in the alpha (7-13 Hz), low-beta (13-20 Hz), and high-beta range (20-30 Hz). In the on-state after levodopa and apomorphine administration, low-beta activity significantly decreased and low-frequency activity increased. In contrast, orphenadrine increased beta activity. Power changes elicited by levodopa and apomorphine at low frequencies and in the beta range were not correlated, whereas changes in the alpha band, which were globally not significant, correlated with the beta rhythm (namely, low beta: 13-20 Hz). In conclusion, in the human STN, there are at least two rhythms below 50 Hz that are separately modulated by antiparkinsonian medication: one at low frequencies and one in the beta range. Multiple rhythms are consistent with the hypothesis of multiple oscillating systems, each possibly correlating with specific aspects of human STN function and dysfunction.

Action Potentials↗

Independent component analysis compared to Laplacian filtering as "deblurring" techniques for event related desynchronization/synchronization.

OBJECTIVES: The aim of the work was to compare two different approaches - one model-dependent, the other data-dependent - for "deblurring" EEG data, in order to improve the estimation of Event-Related Desynchronization/Synchronization. METHODS: Realistic Surface Laplacian filtering (SL) and Infomax Independent Component Analysis (ICA) were applied on multivariate scalp EEG signals (SL: 128 electrodes with MRI-based realistic modeling; ICA: a subset of 19 electrodes, no MRI) prior to beta Event Related Synchronization (ERS) estimation after finger movement in 8 normal subjects. ERS estimation was performed using standard band-pass filtering. ERS peak amplitudes and latencies in the most responsive channel were calculated and the effect of the two methods above was evaluated by one-way analysis of variance (ANOVA) and Sheffe's test. RESULTS: Both methods and their combination significantly improved ERS estimation (greater ERS peak amplitude, p <0.05). The results obtained after ICA on 19 electrodes were not significantly different than the ones obtained with Realistic SL using 128 electrodes and MRI for scalp modeling (p >0.89). CONCLUSIONS: The "low cost" of ICA (19 electrodes, no MRI) imposes such method as a valid alternative to SL filtering. The employ of ICA after SL filtering suggests that the "ideal EEG deblurring method" would unify the two approaches, depending on both the scalp model and the data.

Artifacts↗

300-Hz subthalamic oscillations in Parkinson's disease.

Despite several studies and models, much remains unclear about how the human basal ganglia operate. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for complicated Parkinson's disease, but how DBS acts also remains unknown. The clinical benefit of DBS at frequencies >100 Hz suggests the possible importance of neural rhythms operating at frequencies higher than the range normally considered for basal ganglia processing (<100 Hz). The electrodes implanted for DBS also offer the opportunity to record neural activity from the human basal ganglia. This study aimed to assess whether oscillations at frequencies >100 Hz operate in the human STN. While recording local field potentials from the STN of nine patients with Parkinson's disease through DBS electrodes, we found a dopamine- and movement-dependent 300-Hz rhythm. At rest, and in the absence of dopaminergic medication, in most cases (eight out of 11 nuclei) the 100-1000 Hz band showed no consistent rhythm. Levodopa administration elicited (or markedly increased) a 300-Hz rhythm at rest [(mean +/- SD) central frequency: 319 +/- 33 Hz; bandwidth: 72 +/- 21 Hz; power increase (after medication - before medication)/before medication: 1.30 +/- 1.25; n = 11, P = 0.00098]. The 300-Hz rhythm was also increased by apomorphine, but not by orphenadrine. The 300-Hz rhythm was modulated by voluntary movement. Before levodopa administration, movement-related power increase in the 300-Hz rhythm was variably present in different subjects, whereas after levodopa it became a robust phenomenon [before 0.014 +/- 0.014 arbitrary units (AU), after 0.178 +/- 0.339 AU; n = 8, P = 0.0078]. The dopamine-dependent 300-Hz rhythm probably reflects a bistable compound nuclear activity and supports high-resolution information processing in the basal ganglia circuit. An absent 300-Hz subthalamic rhythm could be a pathophysiological clue in Parkinson's disease. The 300-Hz rhythm also provides the rationale for an excitatory--and not only inhibitory--interpretation of DBS mechanism of action in humans.

Adult↗

Deep brain stimulation for Parkinson's disease: the experience of the Policlinico-San Paolo Group in Milan.

Thirty patients with idiopathic Parkinson's disease were treated with deep brain stimulation electrode in the subthalamic nucleus. After surgery, the patients' best mean Unified Parkinson's Disease Rating Scale (UPDRS III) scores (medictionOFF-stimulatorON versus preoperative medicationOFF) were 77+/-14% at 3 months ( n=20 patients) and 72+/-14% at 12 months follow-up ( n=16). The mean reduction in therapy (expressed in levodopa dose equivalents in mg) was 68+/-25% at 12 months. Postoperative complications were rare, mostly mild, and reversible. Therapeutic success depends on a multidisciplinary team approach, meticulous patient selection, including patients' cognitive, psychic, and behavioral status, and patient and family lifestyles.

Electric Stimulation Therapy↗

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.

Through electrodes implanted for deep brain stimulation in three patients (5 sides) with Parkinson's 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 beta (around 26 Hz), and a low beta (around 18 Hz). The high beta (around 26 Hz) power decreased in the STN and GPi, whereas the low beta (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.

Antiparkinson Agents↗