Are the Symptoms of Parkinsonism Cortical in Origin?

Arbuthnott, G.W.; García‐Muñoz, Marianela

doi:10.1016/j.csbj.2016.10.006

Cited by 10 publications

(12 citation statements)

References 70 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with the involvement of M1 in the pathogenesis of PD, previous studies have described various abnormalities in the M1 of parkinsonian patients and PD models, including increased beta activity of local field potentials and electroencephalogram, 14,30,[41][42][43][44][45][46][47] attenuated motor parameter encoding and increased pairwise synchronization of M1 neurons in MPTPtreated monkeys, 16,35,36,[48][49][50][51] as well as functional imaging abnormalities in the M1 of PD patients. 52 At the population level M1 can be regarded as a dynamic system generating temporally precise sequences of output motor commands in layer 5 PT neurons to control dexterous movements.…”

Section: Discussionsupporting

confidence: 68%

Intrinsic Disruption of the M1 Cortical Network in a Mouse Model of Parkinson's Disease

et al. 2021

View full text Add to dashboard Cite

Background: Parkinson's disease (PD) disrupts motor performance by affecting the basal ganglia system. Yet, despite the critical position of the primary motor cortex in linking basal ganglia computations with motor performance, its contribution to motor disability in PD is largely unknown. The objective of this study was to characterize the role of the primary motor cortex in PD-related motor disability. Methods: Two-photon calcium imaging and optogenetic stimulation of primary motor cortex neurons was done during performance of a dexterous reach-to-grasp motor task in control and 6-hydroxydopamine-induced PD mice. Results: Experimental PD disrupted performance of the reach-to-grasp motor task and especially initiation of the task, which was partially restored by optogenetic activation of the primary motor cortex. Two-photon calcium imaging during task performance revealed experimental-PD affected the primary motor cortex in a cell-typespecific manner. It suppressed activation of output layer 5 pyramidal tract neurons, with greater effects on freeze versus nonfreeze trials. In contrast, it did not attenuate the initial movement-related activation response of layer 2/3 pyramidal neurons while diminishing the late inhibitory phase of their response. At the network level, experimental PD disrupted movement-related population dynamics of the layer 5 pyramidal tract network while almost not affecting the dynamics of the layer 2/3 neuronal population. It also disrupted short-and long-term robustness and stability of the pyramidal tract subnetwork, with reduced intertrial temporal accuracy and diminished reproducibility of motor parameter encoding and temporal recruitment of the output pyramidal tract neurons over repeated daily sessions. Conclusions: Experimental PD disrupts both external driving and intrinsic properties of the primary motor cortex. Motor disability in experimental PD results primarily from the inability to generate robust and stable output motor sequences in the parkinsonian primary motor cortex output layer 5 pyramidal tract subnetwork.

show abstract

Section: Discussionsupporting

confidence: 68%

Intrinsic Disruption of the M1 Cortical Network in a Mouse Model of Parkinson's Disease

et al. 2021

View full text Add to dashboard Cite

show abstract

“…It is being discussed whether the signs and symptoms of parkinsonism have a cortical origin (Arbuthnott & Garcia‐Munoz, ) as abnormal neuronal correlations are recorded in the motor cortex before motor signs of the disease are apparent (Li et al ., ). Some cortical influences over striatal circuitry and its changes during parkinsonism have been described (Calabresi et al ., , ; Hammond et al ., ; Pérez‐Ortega et al ., ).…”

Section: Discussionmentioning

confidence: 99%

“…In dopamine‐depleted animal models, alterations in the synaptic integration of corticostriatal commands have been reported, such as differences in neuronal excitability (Fieblinger et al ., ), distinct corticostriatal synaptic integration (Flores‐Barrera et al ., ), changes in NMDA receptor subunits (Feng et al ., ), altered responses to somatosensory inputs (Ketzef et al ., ) and changes in long‐term plasticity (Picconi et al ., ). Cortical stimulation by several means temporarily improves the parkinsonian state (e.g., Dileone et al ., ), leading some researchers think that the cortex is a main player in the disease (Arbuthnott & Garcia‐Munoz, ; Pérez‐Ortega et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Cortical stimulation relieves parkinsonian pathological activity in vitro

Aparicio-Juárez

Duhne

Lara-González

et al. 2018

Eur J of Neuroscience

View full text Add to dashboard Cite

Previously, we have shown that chemical excitatory drives such as N-methyl-d-aspartate (NMDA) are capable of activating the striatal microcircuit exhibiting neuronal ensembles that alternate their activity producing temporal sequences. One aim of this work was to demonstrate whether similar activity could be evoked by delivering cortical stimulation. Dynamic calcium imaging allowed us to follow the activity of dozens of neurons with single-cell resolution in mus musculus brain slices. A train of electrical stimuli in the cortex evoked network activity similar to the one induced by bath application of NMDA. Previously, we have also shown that the dopamine-depleted striatal microcircuit increases its spontaneous activity generating dominant recurrent ensembles that interrupt the temporal sequences found in control microcircuits. This activity correlates with parkinsonian pathological activity. Several cortical stimulation protocols such as transcranial magnetic stimulation reduce motor signs of Parkinsonism. Here, we show that cortical stimulation in vitro temporarily eliminates the pathological activity from the dopamine-depleted striatal microcircuit by turning off some neurons that sustain this activity and recruiting new ones that allow transitions between network states, similar to the control circuit. When cortical stimulation is given in the presence of L-DOPA, parkinsonian activity is eliminated during the whole recording period. The present experimental evidence suggests that cortical stimulation such as that generated by transcranial magnetic stimulation, or otherwise, may allow reduce L-DOPA dosage.

show abstract

“…These projections might originate in the primary motor cortex or neighboring cortical regions like the supplementary motor area and the dorsal and ventral divisions of the premotor cortex (Nambu et al, 2002). Interestingly, stimulation of cortical layer V neurons reduced Parkinsonian symptoms in mice (Gradinaru et al, 2009), indicating that the motor cortex might play a causal role in the pathogenesis of PD and that DBS of the STN might be effective through antidromic activation of the motor cortex via the hyperdirect pathway (Arbuthnott and Garcia-Munoz, 2017). The amygdala has the potential to influence all three pathways within the basal ganglia due to its connections to the STN, the GP and the motor cortex.…”

Section: Connections Of the Amygdala With Motor Areas And Implicationmentioning

confidence: 99%

Beyond Emotions: Oscillations of the Amygdala and Their Implications for Electrical Neuromodulation

Schönfeld

Wojtecki

2019

Front. Neurosci.

View full text Add to dashboard Cite

The amygdala is a structure involved in emotions, fear, learning and memory and is highly interconnected with other brain regions, for example the motor cortex and the basal ganglia that are often targets of treatments involving electrical stimulation. Deep brain stimulation of the basal ganglia is successfully used to treat movement disorders, but can carry along non-motor side effects. The origin of these non-motor side effects is not fully understood yet, but might be altered oscillatory communication between specific motor areas and the amygdala. Oscillations in various frequency bands have been detected in the amygdala during cognitive and emotional tasks, which can couple with oscillations in cortical regions or the hippocampus. However, data on oscillatory coupling between the amygdala and motor areas are still lacking. This review provides a summary of oscillation frequencies measured in the amygdala and their possible functional relevance in different species, followed by evidence for connectivity between the amygdala and motor areas, such as the basal ganglia and the motor cortex. We hypothesize that the amygdala could communicate with motor areas through coherence of low frequency bands in the theta-alpha range. Furthermore, we discuss a potential role of the amygdala in therapeutic approaches based on electrical stimulation.

show abstract

Are the Symptoms of Parkinsonism Cortical in Origin?

Cited by 10 publications

References 70 publications

Intrinsic Disruption of the M1 Cortical Network in a Mouse Model of Parkinson's Disease

Intrinsic Disruption of the M1 Cortical Network in a Mouse Model of Parkinson's Disease

Cortical stimulation relieves parkinsonian pathological activity in vitro

Beyond Emotions: Oscillations of the Amygdala and Their Implications for Electrical Neuromodulation

Contact Info

Product

Resources

About