scholarly journals Aberrant striatal oscillations after dopamine loss in parkinsonian non-human primates

2019 ◽  
Author(s):  
Arun Singh ◽  
Stella M. Papa
Keyword(s):  
Basal Ganglia ◽  
Oscillatory Activity ◽  
Field Potentials ◽  
Striatal Neurons ◽  
Dopamine Depletion ◽  
Frequency Bands ◽  
Oscillatory Pattern ◽  
Motor Abnormalities ◽  
Beta Frequency

AbstractDopamine depletion in Parkinson’s disease (PD) is associated with abnormal oscillatory activity in the cortico-basal ganglia network. However, the oscillatory pattern of striatal neurons in PD remains poorly defined. Here, we analyzed the local field potentials in one untreated and five MPTP-treated non-human primates (NHP) to model advanced PD. Augmented oscillatory activity in the alpha (8-13 Hz) and low-beta (13-20 Hz) frequency bands was found in the striatum in parallel to the motor cortex and globus pallidus of the NHP-PD model. The coherence analysis showed increased connectivity in the cortico-striatal and striato-pallidal pathways at alpha and low-beta frequency bands, confirming the presence of abnormal 8-20 Hz activity in the cortico-basal ganglia network. The acute L-Dopa injection that induced a clear motor response normalized the amplified 8-20 Hz oscillations. These findings indicate that pathological striatal oscillations at alpha and low-beta bands are concordant with the basal ganglia network changes after dopamine depletion, and thereby support a key role of the striatum in the generation of parkinsonian motor abnormalities.

scholarly journals Dopamine depletion can be predicted by the aperiodic component of subthalamic local field potentials

2021 ◽  
Author(s):  
Jinmo Kim ◽  
Jungmin Lee ◽  
Eunho Kim ◽  
Joon Ho Choi ◽  
Jong-Cheol Rah ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Gamma Oscillations ◽  
Significant Negative Correlation ◽  
Field Potentials ◽  
Dopamine Depletion ◽  
Frequency Oscillation ◽  
Beta Power ◽  
Aperiodic Component ◽  
Beta Frequency ◽  
Nigrostriatal Lesion

Electrophysiological biomarkers reflecting the pathological activities in the basal ganglia are essential to gain an etiological understanding of Parkinson′s disease (PD) and develop a method of diagnosing and treating the disease. Previous studies that explored electrophysiological biomarkers in PD have focused mainly on oscillatory or periodic activities such as beta and gamma oscillations. Emerging evidence has suggested that the nonoscillatory, aperiodic component reflects the firing rate and synaptic current changes corresponding to cognitive and pathological states. Nevertheless, it has never been thoroughly examined whether the aperiodic component can be used as a biomarker that reflect pathological activities in the basal ganglia in PD. In this study, we examined the parameters of the aperiodic component and tested its practicality as an electrophysiological biomarker of pathological activity in PD. We found that a set of aperiodic parameters, aperiodic offset and exponent, were significantly decreased by the nigrostriatal lesion. To further prove the usefulness of the parameters as biomarkers, acute levodopa treatment reverted the aperiodic offset. We then compared the aperiodic parameters with a previously established periodic biomarker of PD, beta frequency oscillation. We found a moderately significant negative correlation with beta power. Finally, taking the aperiodic parameters into account, we could significantly improve the beta power-based prediction of pathological activities in the basal ganglia, demonstrating the validity of these parameters as biomarkers.

scholarly journals Modulation of dopamine tone induces frequency shifts in cortico-basal ganglia beta oscillations

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
L. Iskhakova ◽  
P. Rappel ◽  
M. Deffains ◽  
G. Fonar ◽  
O. Marmor ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Phase Locking ◽  
Oscillatory Activity ◽  
Dopamine Depletion ◽  
Beta Oscillations ◽  
Strongly Coupled ◽  
Beta Power ◽  
Oscillatory Power ◽  
Phase Amplitude ◽  
Beta Frequency

AbstractΒeta oscillatory activity (human: 13–35 Hz; primate: 8–24 Hz) is pervasive within the cortex and basal ganglia. Studies in Parkinson’s disease patients and animal models suggest that beta-power increases with dopamine depletion. However, the exact relationship between oscillatory power, frequency and dopamine tone remains unclear. We recorded neural activity in the cortex and basal ganglia of healthy non-human primates while acutely and chronically up- and down-modulating dopamine levels. We assessed changes in beta oscillations in patients with Parkinson’s following acute and chronic changes in dopamine tone. Here we show beta oscillation frequency is strongly coupled with dopamine tone in both monkeys and humans. Power, coherence between single-units and local field potentials (LFP), spike-LFP phase-locking, and phase-amplitude coupling are not systematically regulated by dopamine levels. These results demonstrate that beta frequency is a key property of pathological oscillations in cortical and basal ganglia networks.

Dynamic Changes in the Cortex-Basal Ganglia Network After Dopamine Depletion in the Rat

2008 ◽  
Vol 100 (1) ◽  
pp. 385-396 ◽  
Author(s):  
Cyril Dejean ◽  
Christian E. Gross ◽  
Bernard Bioulac ◽  
Thomas Boraud
Keyword(s):  
Basal Ganglia ◽  
Local Field ◽  
Signal Transmission ◽  
Local Field Potentials ◽  
Cellular Level ◽  
Cortical Activation ◽  
Field Potentials ◽  
Dopamine Depletion ◽  
Indirect Pathway ◽  
Before And After

It is well established that parkinsonian syndrome is associated with alterations in the temporal pattern of neuronal activity and local field potentials in the basal ganglia (BG). An increase in synchronized oscillations has been observed in different BG nuclei in parkinsonian patients and animal models of this disease. However, the mechanisms underlying this phenomenon remain unclear. This study investigates the functional connectivity in the cortex-BG network of a rodent model of Parkinson's disease. Single neurons and local field potentials were simultaneously recorded in the motor cortex, the striatum, and the substantia nigra pars reticulata (SNr) of freely moving rats, and high-voltage spindles (HVSs) were used to compare signal transmission before and after dopaminergic depletion. It is shown that dopaminergic lesion results in a significant enhancement of oscillatory synchronization in the BG: the coherence between pairs of structures increased significantly and the percentage of oscillatory auto- and cross-correlograms. HVS episodes were also more numerous and longer. These changes were associated with a shortening of the latency of SNr response to cortical activation, from 40.5 ± 4.8 to 10.2 ± 1.07 ms. This result suggests that, in normal conditions, SNr neurons are likely to be driven by late inputs from the indirect pathway; however, after the lesion, their shorter latency also indicates an overactivation of the hyperdirect pathway. This study confirms that neuronal signal transmission is altered in the BG after dopamine depletion but also provides qualitative evidence for these changes at the cellular level.

Effects of Striatal GABAA-Receptor Blockade on Striatal and Cortical Activity in Monkeys

2008 ◽  
Vol 99 (3) ◽  
pp. 1294-1305 ◽  
Author(s):  
Olivier Darbin ◽  
Thomas Wichmann
Keyword(s):  
Single Neuron ◽  
Aminobutyric Acid ◽  
Neuron Activity ◽  
Ionotropic Glutamate Receptor ◽  
Field Potentials ◽  
Striatal Neurons ◽  
Glutamate Receptor Antagonists ◽  
Electrical Activities ◽  
Single Neuron Activity

To elucidate the role of ambient striatal γ-aminobutyric acid (GABA) in the regulation of neuronal activity in the basal ganglia–thalamocortical circuits, we studied the effects of blocking striatal GABAA receptors on the electrical activities of single striatal neurons, on local field potentials (LFPs) in the striatum, and on motor cortical electroencephalograms (EEGs) in two monkeys. Striatal LFPs were recorded with a device that allowed us to simultaneously record field potentials and apply drugs by reverse microdialysis at the same site. Administration of the GABAA-receptor antagonist gabazine (SR95531, 10 and 500 μM) induced large-amplitude LFP fluctuations at the infusion site, occurring every 2–5 s for about 2 h after the start of the 20-min drug administration. These events were prevented by cotreatment with a GABAA-receptor agonist (muscimol, 100 μM) or a combination of ionotropic glutamate receptor antagonists (CNQX and MK-801, each given at 100 μM). Gabazine (10 μM) also increased the firing of single neurons recorded close to the injection site, but in most cases there was no correlation between single-neuron activity and the concomitantly recorded LFP signals from the same striatal region. In contrast, intrastriatal application of gabazine increased the correlation between striatal LFPs and EEG, and resulted in the appearance of recurrent EEG events that were temporally related to the striatal LFP events. These data provide evidence that a GABAergic “tone” in the monkey striatum controls the spontaneous activity of striatal neurons, as well as the level of striatal and cortical synchrony.

scholarly journals Key Modulatory Role of Presynaptic Adenosine A2AReceptors in Cortical Neurotransmission to the Striatal Direct Pathway

2009 ◽  
Vol 9 ◽  
pp. 1321-1344 ◽  
Author(s):  
César Quiroz ◽  
Rafael Luján ◽  
Motokazu Uchigashima ◽  
Ana Patrícia Simoes ◽  
Talia N. Lerner ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Neuropsychiatric Disorders ◽  
Receptor Function ◽  
Striatal Neurons ◽  
Indirect Pathway ◽  
Direct Pathway ◽  
Selective Modulation ◽  
Efferent Pathways

Basal ganglia processing results from a balanced activation of direct and indirect striatal efferent pathways, which are controlled by dopamine D1and D2receptors, respectively. Adenosine A2Areceptors are considered novel antiparkinsonian targets, based on their selective postsynaptic localization in the indirect pathway, where they modulate D2receptor function. The present study provides evidence for the existence of an additional, functionally significant, segregation of A2Areceptors at the presynaptic level. Using integrated anatomical, electrophysiological, and biochemical approaches, we demonstrate that presynaptic A2Areceptors are preferentially localized in cortical glutamatergic terminals that contact striatal neurons of the direct pathway, where they exert a selective modulation of corticostriatal neurotransmission. Presynaptic striatal A2Areceptors could provide a new target for the treatment of neuropsychiatric disorders.

scholarly journals Frequency matters: Up- and Down-Regulation of Dopamine Tone Induces Similar Frequency Shifts in Cortico-Basal Ganglia Beta Oscillations

2020 ◽  
Author(s):  
L. Iskhakova ◽  
P. Rappel ◽  
G. Fonar ◽  
O. Marmor ◽  
R. Paz ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Phase Locking ◽  
Oscillatory Activity ◽  
Dopamine Depletion ◽  
Beta Oscillations ◽  
Similar Frequency ◽  
Strongly Coupled ◽  
Beta Power ◽  
Oscillatory Power ◽  
Network Studies

AbstractBeta oscillatory activity (13-30Hz) is pervasive within the cortico-basal ganglia (CBG) network. Studies in Parkinson’s disease (PD) patients and animal models suggested that beta-power increases with dopamine depletion. However, the exact relationship between oscillatory power, frequency and dopamine-tone remains unclear. We recorded neural activity in the CBG network of non-human-primates (NHP) while acutely up- and down-modulating dopamine levels. Further, we assessed changes in beta oscillations of PD patients following acute and chronic changes in dopamine-tone. Beta oscillation frequency was strongly coupled with dopamine-tone in both NHPs and human patients. In contrast, power, coherence between single-units and LFP, and spike-LFP phase-locking were not systematically regulated by dopamine levels. These results demonstrate via causal manipulations that frequency, rather than other properties, is the key property of pathological oscillations in the CBG networks. These insights can lead to improvements in understanding of CBG physiology, PD progression tracking and patient care.

scholarly journals Neuroleptic Malignant Syndrome Associated with Refractory Acute Disseminated Encephalomyelitis

2016 ◽  
Vol 8 (1) ◽  
pp. 92-96
Author(s):  
Silvia R. Delgado ◽  
Leticia Tornes ◽  
Janice Maldonado ◽  
Jeffrey Hernandez ◽  
Yesica Campos ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Neuroleptic Malignant Syndrome ◽  
Clinical Improvement ◽  
Acute Disseminated Encephalomyelitis ◽  
Dopamine Depletion ◽  
Intravenous Methylprednisolone ◽  
Intravenous Cyclophosphamide ◽  
Inflammatory Lesions ◽  
Significant Clinical Improvement

We present the case of a young man who was transferred to our hospital with worsening acute disseminated encephalomyelitis (ADEM) despite treatment with intravenous methylprednisolone, intravenous immunoglobulin and plasma exchange. He developed neuroleptic malignant syndrome (NMS) without the use of dopamine-modulating drugs. His progressive clinical improvement started after treatment with intravenous cyclophosphamide and methylprednisolone. In our patient, acute demyelination with severe bilateral inflammation of the basal ganglia could have caused a state of central dopamine depletion, creating proper conditions for the development of NMS. Significant clinical improvement of our case after treatment with intravenous cyclophosphamide and steroids provides further evidence for a possible role of the inflammatory lesions in the pathogenesis of NMS in association with ADEM.

Oscillatory Activity and Phase–Amplitude Coupling in the Human Medial Frontal Cortex during Decision Making

2009 ◽  
Vol 21 (2) ◽  
pp. 390-402 ◽  
Author(s):  
Michael X Cohen ◽  
Christian E. Elger ◽  
Juergen Fell
Keyword(s):  
Decision Making ◽  
Frontal Cortex ◽  
Phase Coherence ◽  
Medial Frontal Cortex ◽  
Oscillatory Activity ◽  
Feedback Processing ◽  
Frequency Bands ◽  
Phase Amplitude ◽  
Beta Frequency ◽  
Trial Phase

Electroencephalogram oscillations recorded both within and over the medial frontal cortex have been linked to a range of cognitive functions, including positive and negative feedback processing. Medial frontal oscillatory characteristics during decision making remain largely unknown. Here, we examined oscillatory activity of the human medial frontal cortex recorded while subjects played a competitive decision-making game. Distinct patterns of power and cross-trial phase coherence in multiple frequency bands were observed during different decision-related processes (e.g., feedback anticipation vs. feedback processing). Decision and feedback processing were accompanied by a broadband increase in cross-trial phase coherence at around 220 msec, and dynamic fluctuations in power. Feedback anticipation was accompanied by a shift in the power spectrum from relatively lower (delta and theta) to higher (alpha and beta) power. Power and cross-trial phase coherence were greater following losses compared to wins in theta, alpha, and beta frequency bands, but were greater following wins compared to losses in the delta band. Finally, we found that oscillation power in alpha and beta frequency bands were synchronized with the phase of delta and theta oscillations (“phase–amplitude coupling”). This synchronization differed between losses and wins, suggesting that phase–amplitude coupling might reflect a mechanism of feedback valence coding in the medial frontal cortex. Our findings link medial frontal oscillations to decision making, with relations among activity in different frequency bands suggesting a phase-utilizing coding of feedback valence information.

scholarly journals Anatomical localization of Cav3.1 calcium channels and electrophysiological effects of T-type calcium channel blockade in the motor thalamus of MPTP-treated monkeys

2016 ◽  
Vol 115 (1) ◽  
pp. 470-485 ◽  
Author(s):  
Annaelle Devergnas ◽  
Erdong Chen ◽  
Yuxian Ma ◽  
Ikuma Hamada ◽  
Damien Pittard ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Oscillatory Activity ◽  
Electron Microscopic Level ◽  
Dopamine Depletion ◽  
Frequency Range ◽  
Electron Microscopic ◽  
Motor Thalamus

Conventional anti-Parkinsonian dopamine replacement therapy is often complicated by side effects that limit the use of these medications. There is a continuing need to develop nondopaminergic approaches to treat Parkinsonism. One such approach is to use medications that normalize dopamine depletion-related firing abnormalities in the basal ganglia-thalamocortical circuitry. In this study, we assessed the potential of a specific T-type calcium channel blocker (ML218) to eliminate pathologic burst patterns of firing in the basal ganglia-receiving territory of the motor thalamus in Parkinsonian monkeys. We also carried out an anatomical study, demonstrating that the immunoreactivity for T-type calcium channels is strongly expressed in the motor thalamus in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. At the electron microscopic level, dendrites accounted for >90% of all tissue elements that were immunoreactive for voltage-gated calcium channel, type 3.2-containing T-type calcium channels in normal and Parkinsonian monkeys. Subsequent in vivo electrophysiologic studies in awake MPTP-treated Parkinsonian monkeys demonstrated that intrathalamic microinjections of ML218 (0.5 μl of a 2.5-mM solution, injected at 0.1–0.2 μl/min) partially normalized the thalamic activity by reducing the proportion of rebound bursts and increasing the proportion of spikes in non-rebound bursts. The drug also attenuated oscillatory activity in the 3–13-Hz frequency range and increased gamma frequency oscillations. However, ML218 did not normalize Parkinsonism-related changes in firing rates and oscillatory activity in the beta frequency range. Whereas the described changes are promising, a more complete assessment of the cellular and behavioral effects of ML218 (or similar drugs) is needed for a full appraisal of their anti-Parkinsonian potential.

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