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A Priori

Publications and source records attributed to A Priori.

At least 19 recordsLinked to original sources
PubMed2006

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↗
PubMed2006

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↗
PubMed2006

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↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2005

Non-synaptic mechanisms underlie the after-effects of cathodal transcutaneous direct current stimulation of the human brain.

Although cathodal transcranial direct current stimulation (tDCS) decreases cortical excitability, the mechanisms underlying DC-induced changes remain largely unclear. In this study we investigated the effect of cathodal DC stimulation on spontaneous neural activity and on motor responses evoked by stimulation of the central and peripheral nervous system. We studied 17 healthy volunteers. Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) of the motor area were used to study the effects of cathodal tDCS (1.5 mA, 10 min) on resting motor threshold and motor evoked potentials (MEPs) recorded from the contralateral first dorsal interosseous muscle (FDI). The electroencephalographic (EEG) activity in response to cathodal tDCS was analysed by power spectral density (PSD). Motor axonal excitability changes in response to transcutaneous DC stimulation of the ulnar nerve (0.3 mA, 10 min) were assessed by testing changes in the size of the compound muscle action potential (CMAP) elicited by submaximal nerve stimulation. Cathodal tDCS over the motor area for 10 min increased the motor threshold and decreased the size of MEPs evoked by TMS for at least 60 min after current offset (t(0) 71.7 +/- 5%, t(20) 50.8 +/- 11%, t(40) 47.7 +/- 7.7%, and t(60) 39.7 +/- 6.4%, P < 0.01). The tDCS also significantly decreased the size of MEPs elicited by TES (t(0) 64 +/- 16.4%, P = 0.09; t(20) 67.6 +/- 10.8%, P = 0.06; and t(40) 58.3 +/- 9.9%, P < 0.05). At the same time in the EEG the power of delta (2-4 Hz) and theta (4-7 Hz) rhythms increased (delta 181.1 +/- 40.2, P < 0.05; and theta 138.7 +/- 27.6, P = 0.07). At the peripheral level cathodal DC stimulation increased the size of the ulnar nerve CMAP (175 +/- 34.3%, P < 0.05). Our findings demonstrate that the after-effects of tDCS have a non-synaptic mechanism of action based upon changes in neural membrane function. These changes apart from reflecting local changes in ionic concentrations, could arise from alterations in transmembrane proteins and from electrolysis-related changes in [H(+)] induced by exposure to constant electric field.

Adult↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2004

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

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-to-noise 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.

Aged↗
PubMed2004

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↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

Paired transcranial magnetic stimulation for the early diagnosis of corticobasal degeneration.

OBJECTIVE: To investigate cortical excitability in patients with corticobasal degeneration (CBD) and to find a reliable diagnostic technique for differentiating CBD from Parkinson's disease (PD). METHODS: Using a paired transcranial magnetic stimulation technique, we studied motor cortex excitability at rest in 6 patients with clinically probable CBD, 10 patients with PD, and 10 normal subjects. The recovery cycle of the motor evoked potentials was tested by delivering paired magnetic stimulation over the hand area of the motor cortex at interstimulus intervals (ISIs) from 1 to 17ms. RESULTS: In patients with CBD, paired magnetic stimuli delivered at short ISIs invariably elicited enlarged test MEPs. At ISIs of 1-10ms, the conditioned test MEPs were significantly larger in patients with CBD than in control subjects; and at ISIs of 1, 2, 4, and 6ms,they were also larger in patients with CBD than in patients with PD. At the other ISIs tested, patients and control subjects had similar amplitude conditioned test responses. CONCLUSIONS: Our findings suggest that the unusual clinical manifestations of CBD might arise partly from motor cortex disinhibition. Paired magnetic stimulation could be a useful diagnostic test particularly in the early stages of the disease.

Aged↗
PubMed2003

Multiple sequential image-fusion and direct MRI localisation of the subthalamic nucleus for deep brain stimulation.

AIM: Deep brain stimulation (DBS) is the treatment of choice for advanced Parkinson's disease. The target co-ordinates are traditionally calculated in relation to the intercommissural distance. Anterior (AC) and posterior commissures (PC) may be visualised by the means of ventriculography, CT or MRI. METHODS: We have studied the efficacy of direct visualisation of the subthalamic-red nucleus complex on MRI, the advantage of fusion of stereotactic CT and MR images (Multiple Sequences Image Fusion - MuSIF). These methods are combined with double check of indirect calculation of the target co-ordinates based on AC-PC line, as well as the corrispondence to the stereotactic electronic atlas. RESULTS: Subthalamic nucleus (STN) was well recognisable in fused images in all 22 sides. At 3 months from surgery it was possible to reduce 76% of L-dopa equivalent daily dose. Dyskine-sias reduced to 50% and motor fluctuation up to 45%. CONCLUSION: In our experience MuSIF offers very high rate of accuracy in calculation of target co-ordinates. Direct visualisation of STN in MR and MuSIF are reliable and facilitate the accuracy of identification of target co-ordinates. Intraoperative neurophysiological recording increases the accuracy of microelectrode position.

Antiparkinson Agents↗
PubMed2003

Do intraoperative microrecordings improve subthalamic nucleus targeting in stereotactic neurosurgery for Parkinson's disease?

AIM: The clinical importance of intraoperative microrecordings for subthalamic nucleus (STN) localization in neurosurgical practice remains a matter of debate in the various groups. METHODS: To investigate their usefulness in localizing the STN, we retrospectively evaluated how intraoperative microelectrode recordings changed the targeting of the STN estimated only on intraoperative stimulation and neuroanatomic targeting procedures. For neuroradiologic targeting of the nucleus we used a TC-MRI fusion algorithm and direct visualization of the STN. Besides standard microrecordings we also analyzed the power spectral density (PSD) pattern of physiological signals along the track and its neuroanatomic and clinical correlations. RESULTS: In our series of 12 patients with Parkinson's disease undergoing surgery for implantation of deep-brain stimulation (DBS) electrodes in the STN we found that in 25% (1/4) of patients, microrecordings determined the choice of the optimal track. In all the tracks analyzed the PSD peak coincided with the point selected for the final electrode implantation on the basis of the standard procedure for intraoperative monitoring based on both microstimulation and recordings. CONCLUSION: Intraoperative microrecordings are of determinant importance for accurate STN localization and are essential for optimal results in neurosurgical practice. PSD analysis is a simple and quick quantitative signal descriptor that will probably provide even more precise, simple and rapid tool for intraoperative neurophysiological localization of the STN.

Electrodes, Implanted↗
PubMed2002

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

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 Parkinson's 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 literature's 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 patient's STN anatomy.

Electrodes, Implanted↗