Exaggerated phase-amplitude coupling in the primary motor cortex in Parkinson disease.
Ontology highlight
ABSTRACT:
SUBMITTER: de Hemptinne C
PROVIDER: S-EPMC3606991 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ObjectiveRecent discoveries suggest that it is most likely the coupling of β oscillations (13-30Hz) and not merely their power that relates to Parkinson disease (PD) pathophysiology.MethodsWe analyzed power and phase amplitude coupling (PAC) in local field potentials (LFP) recorded from Pallidum after placement of deep brain stimulation (DBS) leads in nineteen PD patients and three patients with dystonia.ResultsWithin GPi, we identified PAC between phase of β and amplitude of high frequency oscillations (200-300Hz) and distinct β-low γ (40-80Hz) PAC both modulated by contralateral movement. Resting β-low γ PAC, also present in dystonia patients, inversely correlated with severity of rigidity and bradykinesia (R=-0.44, P=0.028). These findings were specific to the low β band, suggesting a differential role for the two β sub-bands.ConclusionsPAC is present across distinct frequency bands within the GPi. Given the presence of low β-low γ PAC in dystonia and the inverse correlation with symptom severity, we propose that this PAC may be a normal pallidal signal.SignificanceThis study provides new evidence on the pathophysiological contribution of local pallidal coupling and suggests similar and distinct patterns of coupling within GPi and STN in PD.
| S-EPMC5675765 | biostudies-literature
Project description:ObjectiveHigh-amplitude beta band oscillations within the subthalamic nucleus are frequently associated with Parkinson's disease but it is unclear how they might lead to motor impairments. Here we investigate a likely pathological coupling between the phase of beta band oscillations and the amplitude of high-frequency oscillations around 300 Hz.MethodsWe analysed an extensive data set comprising resting-state recordings obtained from deep brain stimulation electrodes in 33 patients before and/or after taking dopaminergic medication. We correlated mean values of spectral power and phase-amplitude coupling with severity of hemibody bradykinesia/rigidity. In addition, we used simultaneously recorded magnetoencephalography to look at functional interactions between the subthalamic nucleus and ipsilateral motor cortex.ResultsBeta band power and phase-amplitude coupling within the subthalamic nucleus correlated positively with severity of motor impairment. This effect was more pronounced within the low-beta range, whilst coherence between subthalamic nucleus and motor cortex was dominant in the high-beta range.ConclusionsWe speculate that the beta band might impede pro-kinetic high-frequency activity patterns when phase-amplitude coupling is prominent. Furthermore, results provide evidence for a functional subdivision of the beta band into low and high frequencies.SignificanceOur findings contribute to the interpretation of oscillatory activity within the cortico-basal ganglia circuit.
| S-EPMC4803022 | biostudies-literature
Project description:Oscillatory neural activity in different frequency bands and phase-amplitude coupling (PAC) are hypothesized to be biomarkers of Parkinson's disease (PD) that could explain dysfunction in the motor circuit and be used for closed-loop deep brain stimulation (DBS). How these putative biomarkers change from the normal to the parkinsonian state across nodes in the motor circuit and within the same subject, however, remains unknown. In this study, we characterized how parkinsonism and vigilance altered oscillatory activity and PAC within the primary motor cortex (M1), subthalamic nucleus (STN), and globus pallidus (GP) in two nonhuman primates. Static and dynamic analyses of local field potential (LFP) recordings indicate that 1) after induction of parkinsonism using the neurotoxin MPTP, low-frequency power (8-30 Hz) increased in the STN and GP in both subjects, but increased in M1 in only one subject; 2) high-frequency power (~330 Hz) was present in the STN in both normal subjects but absent in the parkinsonian condition; 3) elevated PAC measurements emerged in the parkinsonian condition in both animals, but in different sites in each animal (M1 in one subject and GPe in the other); and 4) the state of vigilance significantly impacted how oscillatory activity and PAC were expressed in the motor circuit. These results support the hypothesis that changes in low- and high-frequency oscillatory activity and PAC are features of parkinsonian pathophysiology and provide evidence that closed-loop DBS systems based on these biomarkers may require subject-specific configurations as well as adaptation to changes in vigilance.NEW & NOTEWORTHY Chronically implanted electrodes were used to record neural activity across multiple nodes in the basal ganglia-thalamocortical circuit simultaneously in a nonhuman primate model of Parkinson's disease, enabling within-subject comparisons of electrophysiological biomarkers between normal and parkinsonian conditions and different vigilance states. This study improves our understanding of the role of oscillatory activity and phase-amplitude coupling in the pathophysiology of Parkinson's disease and supports the development of more effective DBS therapies based on pathophysiological biomarkers.
| S-EPMC5672540 | biostudies-literature
Project description:To characterize Parkinson's disease, abnormal phase-amplitude coupling is assessed in the cortico-basal circuit using invasive recordings. It is unknown whether the same phenomenon might be found in regions other than the cortico-basal ganglia circuit. We hypothesized that using magnetoencephalography to assess phase-amplitude coupling in the whole brain can characterize Parkinson's disease. We recorded resting-state magnetoencephalographic signals in patients with Parkinson's disease and in healthy age- and sex-matched participants. We compared whole-brain signals from the two groups, evaluating the power spectra of 3 frequency bands (alpha, 8-12 Hz; beta, 13-25 Hz; gamma, 50-100 Hz) and the coupling between gamma amplitude and alpha or beta phases. Patients with Parkinson's disease showed significant beta-gamma phase-amplitude coupling that was widely distributed in the sensorimotor, occipital, and temporal cortices; healthy participants showed such coupling only in parts of the somatosensory and temporal cortices. Moreover, beta- and gamma-band power differed significantly between participants in the two groups (P < 0.05). Finally, beta-gamma phase-amplitude coupling in the sensorimotor cortices correlated significantly with motor symptoms of Parkinson's disease (P < 0.05); beta- and gamma-band power did not. We thus demonstrated that beta-gamma phase-amplitude coupling in the resting state characterizes Parkinson's disease.
| S-EPMC8813926 | biostudies-literature
Project description:Dopamine release and phase-amplitude cross-frequency coupling (CFC) have independently been implicated in prefrontal cortex (PFC) functioning. To causally investigate whether dopamine release affects phase-amplitude comodulation between different frequencies in local field potentials (LFP) recorded from the medial PFC (mPFC) of behaving rats, we used RuBiDopa, a light-sensitive caged compound that releases the neurotransmitter dopamine when irradiated with visible light. LFP power did not change in any frequency band after the application of light-uncaged dopamine, but significantly strengthened phase-amplitude comodulation between delta and gamma oscillations. Saline did not exert significant changes, while injections of dopamine and RuBiDopa produced a slow increase in comodulation for several minutes after the injection. The results show that dopamine release in the medial PFC shifts phase-amplitude comodulation from theta-gamma to delta-gamma. Although being preliminary results due to the limitation of the low number of animals present in this study, our findings suggest that dopamine-mediated modification of the frequencies involved in comodulation could be a mechanism by which this neurotransmitter regulates functioning in mPFC.
| S-EPMC5422429 | biostudies-literature
Project description:Attention is a core cognitive mechanism that allows the brain to allocate limited resources depending on current task demands. A number of frontal and posterior parietal cortical areas, referred to collectively as the fronto-parietal attentional control network, are engaged during attentional allocation in both humans and non-human primates. Numerous studies have examined this network in the human brain using various neuroimaging and scalp electrophysiological techniques. However, little is known about how these frontal and parietal areas interact dynamically to produce behavior on a fine temporal (sub-second) and spatial (sub-centimeter) scale. We addressed how human fronto-parietal regions control visuospatial attention on a fine spatiotemporal scale by recording electrocorticography (ECoG) signals measured directly from subdural electrode arrays that were implanted in patients undergoing intracranial monitoring for localization of epileptic foci. Subjects (n = 8) performed a spatial-cuing task, in which they allocated visuospatial attention to either the right or left visual field and detected the appearance of a target. We found increases in high gamma (HG) power (70-250 Hz) time-locked to trial onset that remained elevated throughout the attentional allocation period over frontal, parietal, and visual areas. These HG power increases were modulated by the phase of the ongoing delta/theta (2-5 Hz) oscillation during attentional allocation. Critically, we found that the strength of this delta/theta phase-HG amplitude coupling predicted reaction times to detected targets on a trial-by-trial basis. These results highlight the role of delta/theta phase-HG amplitude coupling as a mechanism for sub-second facilitation and coordination within human fronto-parietal cortex that is guided by momentary attentional demands.
| S-EPMC4144794 | biostudies-literature
Project description:ObjectiveWe hypothesized that subthalamic nucleus (STN) deep brain stimulation (DBS) will improve long-term potentiation (LTP)-like plasticity in motor cortex in Parkinson disease (PD).MethodsWe studied 8 patients with PD treated with STN-DBS and 9 age-matched healthy controls. Patients with PD were studied in 4 sessions in medication (Med) OFF/stimulator (Stim) OFF, Med-OFF/Stim-ON, Med-ON/Stim-OFF, and Med-ON/Stim-ON states in random order. Motor evoked potential amplitude and cortical silent period duration were measured at baseline before paired associated stimulation (PAS) and at 3 different time intervals (T0, T30, T60) up to 60 minutes after PAS in the abductor pollicis brevis and abductor digiti minimi muscles.ResultsMotor evoked potential size significantly increased after PAS in controls (+67.7% of baseline at T30) and in patients in the Med-ON/Stim-ON condition (+55.8% of baseline at T30), but not in patients in the Med-OFF/Stim-OFF (-0.4% of baseline at T30), Med-OFF/Stim-ON (+10.3% of baseline at T30), and Med-ON/Stim-OFF conditions (+17.3% of baseline at T30). Cortical silent period duration increased after PAS in controls but not in patients in all test conditions.ConclusionsOur findings suggest that STN-DBS together with dopaminergic medications restore LTP-like plasticity in motor cortex in PD. Restoration of cortical plasticity may be one of the mechanisms of how STN-DBS produces clinical benefit.
| S-EPMC4534071 | biostudies-literature
Project description:Deep brain stimulation (DBS) is increasingly applied for the treatment of brain disorders, but its mechanism of action remains unknown. Here we evaluate the effect of basal ganglia DBS on cortical function using invasive cortical recordings in Parkinson's disease (PD) patients undergoing DBS implantation surgery. In the primary motor cortex of PD patients, neuronal population spiking is excessively synchronized to the phase of network oscillations. This manifests in brain surface recordings as exaggerated coupling between the phase of the beta rhythm and the amplitude of broadband activity. We show that acute therapeutic DBS reversibly reduces phase-amplitude interactions over a similar time course as that of the reduction in parkinsonian motor signs. We propose that DBS of the basal ganglia improves cortical function by alleviating excessive beta phase locking of motor cortex neurons.
| S-EPMC4414895 | biostudies-literature
Project description:The level of activity of many animals including humans rises and falls with a period of ~ 24 hours. The intrinsic biological oscillator that gives rise to this circadian oscillation is driven by a molecular feedback loop with an approximately 24 hour cycle period and is influenced by the environment, most notably the light:dark cycle. In addition to the circadian oscillations, behavior of many animals is influenced by multiple oscillations occurring at faster-ultradian-time scales. These ultradian oscillations are also thought to be driven by feedback loops. While many studies have focused on identifying such ultradian oscillations, less is known about how the ultradian behavioral oscillations interact with each other and with the circadian oscillation. Decoding the coupling among the various physiological oscillators may be important for understanding how they conspire together to regulate the normal activity levels, as well in disease states in which such rhythmic fluctuations in behavior may be disrupted. Here, we use a wavelet-based cross-frequency analysis to show that different oscillations identified in spontaneous mouse behavior are coupled such that the amplitude of oscillations occurring at higher frequencies are modulated by the phase of the slower oscillations. The patterns of these interactions are different among different individuals. Yet this variability is not random. Differences in the pattern of interactions are confined to a low dimensional subspace where different patterns of interactions form clusters. These clusters expose the differences among individuals-males and females are preferentially segregated into different clusters. These sex-specific features of spontaneous behavior were not apparent in the spectra. Thus, our methodology reveals novel aspects of the structure of spontaneous animal behavior that are not observable using conventional methodology.
| S-EPMC5025157 | biostudies-literature
Project description:Analysis of the coupling between the phases and amplitudes of oscillations within the same continuously sampled signal has provided interesting insights into the physiology of memory and other brain process, and, more recently, the pathophysiology of parkinsonism and other movement disorders. Technical aspects of the analysis have a significant impact on the results. We present an empirical exploration of a variety of analysis design choices that need to be considered when measuring phase-amplitude coupling (PAC). We studied three alternative filtering approaches to the commonly used Kullback-Leibler distance-based method of PAC analysis, including one method that uses wavelets, one that uses constant filter settings, and one in which filtering of the data is optimized for individual frequency bands. Additionally, we introduce a time-dependent PAC analysis technique that takes advantage of the inherent temporality of wavelets. We examined how the duration of the sampled data, the stability of oscillations, or the presence of artifacts affect the value of the "modulation index", a commonly used parameter describing the degree of PAC. We also studied the computational costs associated with calculating modulation indices by the three techniques. We found that wavelet-based PAC performs better with similar or less computational cost than the two other methods while also allowing to examine temporal changes of PAC. We also show that the reliability of PAC measurements strongly depends on the duration and stability of PAC, and the presence (or absence) of artifacts. The best parameters to be used for PAC analyses of long samples of data may differ, depending on data characteristics and analysis objectives. Prior to settling on a specific PAC analysis approach for a given set of data, it may be useful to conduct an initial analysis of the time-dependence of PAC using our time-resolved PAC analysis.
| S-EPMC6615623 | biostudies-literature