Miguel Valencia

Coupling between Beta and High-Frequency Activity in the Human Subthalamic Nucleus May Be a Pathophysiological Mechanism in Parkinson's Disease

In Parkinsons disease (PD), the oscillatory activity recorded from the basal ganglia shows dopamine-dependent changes. In the “off” parkinsonian motor state, there is prominent activity in the beta band (12–30 Hz) that is mostly attenuated after dopaminergic therapy (“on” medication state). The on state is also characterized by activity in the gamma (60–80 Hz) and high-frequency (300 Hz) bands that is modulated by movement. We recorded local field potentials from a group of 15 PD patients (three females) treated with bilateral deep brain stimulation of the subthalamic nucleus, using a high sampling rate (2 kHz) and filters suitable to study high-frequency activity (0.3–1000 Hz). We observed high-frequency oscillations (HFOs) in both the off and on motor states. In the off state, the amplitude of the HFOs was coupled to the phase of the abnormal beta activity. The beta-coupled HFOs showed little or even negative movement-related changes in amplitude. Moreover, the degree of movement-related modulation of the HFOs correlated negatively with the rigidity/bradykinesia scores. In the on motor state, the HFOs were liberated from this beta coupling, and they displayed marked movement-related amplitude modulation. Cross-frequency interactions between the phase of slow activities and the amplitude of fast frequencies have been attributed an important role in information processing in cortical structures. Our findings suggest that nonlinear coupling between frequencies may not only be a physiological mechanism (as shown previously) but also that it may participate in the pathophysiology of parkinsonism.

Independent component analysis as a tool to eliminate artifacts in EEG: A quantitative study

Summary Independent component analysis (ICA) is a novel technique that calculates independent components from mixed signals. A hypothetical clinical application is to remove artifacts in EEG. The goal of this study was to apply ICA to standard EEG recordings to eliminate well-known artifacts, thus quantifying its efficacy in an objective way. Eighty samples of recordings with spikes and evident artifacts of electrocardiogram (EKG), eye movements, 50-Hz interference, muscle, or electrode artifact were studied. ICA components were calculated using the Joint Approximate Diagonalization of Eigen-matrices (JADE) algorithm. The signal was reconstructed excluding those components related to the artifacts. A normalized correlation coefficient was used as a measure of the changes caused by the suppression of these components. ICA produced an evident clearing-up of signals in all the samples. The morphology and the topography of the spike were very similar before and after the removal of the artifacts. The correlation coefficient showed that the rest of the signal did not change significantly. Two examiners independently looked at the samples to identify the changes in the morphology and location of the discharge and the artifacts. In conclusion, ICA proved to be a useful tool to clean artifacts in short EEG samples, without having the disadvantages associated with the digital filters. The distortion of the interictal activity measured by correlation analysis was minimal.

Functional modularity of background activities in normal and epileptic brain networks.

We analyze the connectivity structure of weighted brain networks extracted from spontaneous magnetoencephalographic signals of healthy subjects and epileptic patients (suffering from absence seizures) recorded at rest. We find that, for the activities in the 5-14 Hz range, healthy brains exhibit a sparse connectivity, whereas the brain networks of patients display a rich connectivity with a clear modular structure. Our results suggest that modularity plays a key role in the functional organization of brain areas during normal and pathological neural activities at rest.

Movement-related changes in oscillatory activity in the human subthalamic nucleus : ipsilateral vs. contralateral movements

A voluntary movement is accompanied by a series of changes in neuronal oscillatory activity in the subthalamic nucleus (STN). These changes can be recorded through electrodes implanted for deep brain stimulation to treat Parkinsons disease in the time interval between the surgery and the internalization of the connections to the batteries. Both baseline activity and movement‐related changes are different in the ‘on’ and ‘off’ medication motor states. In the ‘off’ state a low frequency activity in the alpha–beta range (8–25 Hz) that dominates the spectrum is interrupted during the movement, while in the ‘on’ state baseline frequencies are higher and a peri‐movement gamma increase (70–80 Hz) is usually observed. Similar changes have been described with electrocorticographic recordings over the primary motor cortex but the gamma increase was only present during contralateral movements. We compared ipsi‐ and contralateral movement‐related changes in STN activity, using a time–frequency analysis of the recordings obtained simultaneously in both STN and the scalp (electroencephalography) during right and left hand movements. The movement‐related changes observed in the STN in the ‘on’ and the ‘off’ states were similar to those described previously in terms of predominant frequency bands, but we found bilateral changes in the STN during movements of either hand. A contralateral earlier start of the beta STN changes was mostly observed when the moving hand corresponded to the less‐affected side, irrespective of hand dominance. These results suggest that movement‐related activity in the STN has, by and large, a bilateral representation and probably reflects cortical input.

Independent component analysis removing artifacts in ictal recordings

Summary:  Purpose: Independent component analysis (ICA) is a novel algorithm able to separate independent components from complex signals. Studies in interictal EEG demonstrate its usefulness to eliminate eye, muscle, 50‐Hz, electrocardiogram (ECG), and electrode artifacts. The goal of this study was to evaluate the usefulness of ICA in removing artifacts in ictal recordings with a known EEG onset.

Frontal and central oscillatory changes related to different aspects of the motor process: a study in go/no-go paradigms

We studied alpha and beta EEG oscillatory changes in healthy volunteers during two different auditory go/no-go paradigms, in order to investigate their relationship with different components of the motor process. In the first paradigm (S2-centered), the initial tone (S1) was constant (warning), and the second tone (S2) indicated the subject whether to move or not. In the second paradigm (S1-centered), S1 indicated whether to move or not, while S2 just indicated the timing of the movement. A medial frontal beta energy increase was found in all conditions after the stimulus that forces the subject to decide whether to move or not (S1 or S2 depending on the paradigm). In both go conditions, a central alpha and beta energy decrease began after the go decision, reaching minimum values during the movement; it was followed by a beta post-movement increase, limited to the central contralateral area. In the no-go conditions, a marked fronto-central beta synchronization appeared after the decision not to move. In conclusion, our study was able to dissociate the beta oscillatory changes related to movement preparation and execution (central decrease/increase) from those associated with decision-making (medial frontal increase) and motor inhibition (fronto-central increase).

Remote synchronization reveals network symmetries and functional modules

We study a Kuramoto model in which the oscillators are associated with the nodes of a complex network and the interactions include a phase frustration, thus preventing full synchronization. The system organizes into a regime of remote synchronization where pairs of nodes with the same network symmetry are fully synchronized, despite their distance on the graph. We provide analytical arguments to explain this result, and we show how the frustration parameter affects the distribution of phases. An application to brain networks suggests that anatomical symmetry plays a role in neural synchronization by determining correlated functional modules across distant locations.

Ketamine-Induced Oscillations in the Motor Circuit of the Rat Basal Ganglia

Oscillatory activity can be widely recorded in the cortex and basal ganglia. This activity may play a role not only in the physiology of movement, perception and cognition, but also in the pathophysiology of psychiatric and neurological diseases like schizophrenia or Parkinsons disease. Ketamine administration has been shown to cause an increase in gamma activity in cortical and subcortical structures, and an increase in 150 Hz oscillations in the nucleus accumbens in healthy rats, together with hyperlocomotion. We recorded local field potentials from motor cortex, caudate-putamen (CPU), substantia nigra pars reticulata (SNr) and subthalamic nucleus (STN) in 20 awake rats before and after the administration of ketamine at three different subanesthetic doses (10, 25 and 50 mg/Kg), and saline as control condition. Motor behavior was semiautomatically quantified by custom-made software specifically developed for this setting. Ketamine induced coherent oscillations in low gamma (50 Hz), high gamma (80 Hz) and high frequency (HFO, 150 Hz) bands, with different behavior in the four structures studied. While oscillatory activity at these three peaks was widespread across all structures, interactions showed a different pattern for each frequency band. Imaginary coherence at 150 Hz was maximum between motor cortex and the different basal ganglia nuclei, while low gamma coherence connected motor cortex with CPU and high gamma coherence was more constrained to the basal ganglia nuclei. Power at three bands correlated with the motor activity of the animal, but only coherence values in the HFO and high gamma range correlated with movement. Interactions in the low gamma band did not show a direct relationship to movement. These results suggest that the motor effects of ketamine administration may be primarily mediated by the induction of coherent widespread high-frequency activity in the motor circuit of the basal ganglia, together with a frequency-specific pattern of connectivity among the structures analyzed.

High beta activity in the subthalamic nucleus and freezing of gait in Parkinson's disease.

OBJECTIVE Oscillatory activity in the beta band is increased in the subthalamic nucleus (STN) of Parkinsons disease (PD) patients. Rigidity and bradykinesia are associated with the low-beta component (13-20Hz) but the neurophysiological correlate of freezing of gait in PD has not been ascertained. METHODS We evaluated the power and coherence of the low- and high-beta bands in the STN and cortex (EEG) of PD patients with (p-FOG) (n=14) or without freezing of gait (n-FOG) (n=8) in whom electrodes for chronic stimulation in the STN had been implanted for treatment with deep brain stimulation. RESULTS p-FOG patients showed higher power in the high-beta band (F=11.6, p=0.002) that was significantly reduced after l-dopa administration along with suppression of FOG (F=4.6, p=0.042). High-beta cortico-STN coherence was maximal for midline cortical EEG electrodes, whereas the low-beta band was maximal for lateral electrodes (χ(2)=20.60, p<0.0001). CONCLUSIONS The association between freezing of gait, high-beta STN oscillations and cortico-STN coherence suggests that this oscillatory activity might interfere in the frontal cortex-basal ganglia networks, thereby participating in the pathophysiology of FOG in PD.

Segregated cholinergic transmission modulates dopamine neurons integrated in distinct functional circuits.

Dopamine neurons in the ventral tegmental area (VTA) receive cholinergic innervation from brainstem structures that are associated with either movement or reward. Whereas cholinergic neurons of the pedunculopontine nucleus (PPN) carry an associative/motor signal, those of the laterodorsal tegmental nucleus (LDT) convey limbic information. We used optogenetics and in vivo juxtacellular recording and labeling to examine the influence of brainstem cholinergic innervation of distinct neuronal subpopulations in the VTA. We found that LDT cholinergic axons selectively enhanced the bursting activity of mesolimbic dopamine neurons that were excited by aversive stimulation. In contrast, PPN cholinergic axons activated and changed the discharge properties of VTA neurons that were integrated in distinct functional circuits and were inhibited by aversive stimulation. Although both structures conveyed a reinforcing signal, they had opposite roles in locomotion. Our results demonstrate that two modes of cholinergic transmission operate in the VTA and segregate the neurons involved in different reward circuits.