scholarly journals Roles of Motor Cortex Neuron Classes in Reach-Related Modulation for Hemiparkinsonian Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Min Li ◽  
Xuenan Wang ◽  
Xiaomeng Yao ◽  
Xiaojun Wang ◽  
Feiyu Chen ◽  
...  

Disruption of the function of the primary motor cortex (M1) is thought to play a critical role in motor dysfunction in Parkinson’s disease (PD). Detailed information regarding the specific aspects of M1 circuits that become abnormal is lacking. We recorded single units and local field potentials (LFPs) of M1 neurons in unilateral 6-hydroxydopamine (6-OHDA) lesion rats and control rats to assess the impact of dopamine (DA) cell loss during rest and a forelimb reaching task. Our results indicated that M1 neurons can be classified into two groups (putative pyramidal neurons and putative interneurons) and that 6-OHDA could modify the activity of different M1 subpopulations to a large extent. Reduced activation of putative pyramidal neurons during inattentive rest and reaching was observed. In addition, 6-OHDA intoxication was associated with an increase in certain LFP frequencies, especially those in the beta range (broadly defined here as any frequency between 12 and 35 Hz), which become pathologically exaggerated throughout cortico-basal ganglia circuits after dopamine depletion. Furthermore, assessment of different spike-LFP coupling parameters revealed that the putative pyramidal neurons were particularly prone to being phase-locked to ongoing cortical oscillations at 12–35 Hz during reaching. Conversely, putative interneurons were neither hypoactive nor synchronized to ongoing cortical oscillations. These data collectively demonstrate a neuron type-selective alteration in the M1 in hemiparkinsonian rats. These alterations hamper the ability of the M1 to contribute to motor conduction and are likely some of the main contributors to motor impairments in PD.

2021 ◽  
Vol 13 ◽  
Author(s):  
Kaixuan Shi ◽  
Xiaoli Liu ◽  
Lijuan Hou ◽  
Decai Qiao ◽  
Yuan Peng

Aberrant cortical spike-local field potential (LFP) coupling leads to abnormal basal ganglia activity, disruption of cortical function, and impaired movement in Parkinson's disease (PD). Here, the primary motor cortex mediated plasticity mechanism underlying behavioral improvement by exercise intervention was investigated. Exercise alleviates motor dysfunction and induces neuroplasticity in PD. In this study, Sprague-Dawley (SD) rats were injected with 6-hydroxydopamine (6-OHDA) to induce unilateral nigrostriatal dopamine depletion. Two weeks later, a 4-week exercise intervention was initiated in the PD + exercise (Ex) group. Multichannel recording technology recorded spikes and LFPs in rat motor cortices, and balanced ability tests evaluated behavioral performance. The balanced ability test showed that the total crossing time/front leg error/input latency time was significantly lower in PD + Ex rats than in PD rats (P < 0.05). Scalograms and LFP power spectra indicated increased beta-range LFP power in lesioned hemispheres, with exercise reducing LFP power spectral density. Spike-triggered LFP waveform averages showed strong phase-locking in PD motor cortex cells, and exercise reduced spike-LFP synchronization. Our results suggest that exercise can suppress overexcitability of LFPs and minimize spike-LFP synchronization in the motor cortex, leading to motor-improving effects in PD.


2013 ◽  
Vol 110 (12) ◽  
pp. 2792-2805 ◽  
Author(s):  
C. J. Lobb ◽  
A. K. Zaheer ◽  
Y. Smith ◽  
D. Jaeger

Numerous studies have suggested that alpha-synuclein plays a prominent role in both familial and idiopathic Parkinson's disease (PD). Mice in which human alpha-synuclein is overexpressed (ASO) display progressive motor deficits and many nonmotor features of PD. However, it is unclear what in vivo pathophysiological mechanisms drive these motor deficits. It is also unknown whether previously proposed pathophysiological features (i.e., increased beta oscillations, bursting, and synchronization) described in toxin-based, nigrostriatal dopamine-depletion models are also present in ASO mice. To address these issues, we first confirmed that 5- to 6-mo-old ASO mice have robust motor dysfunction, despite the absence of significant nigrostriatal dopamine degeneration. In the same animals, we then recorded simultaneous single units and local field potentials (LFPs) in the substantia nigra pars reticulata (SNpr), the main basal ganglia output nucleus, and one of its main thalamic targets, the ventromedial nucleus, as well as LFPs in the primary motor cortex in anesthetized ASO mice and their age-matched, wild-type littermates. Neural activity was examined during slow wave activity and desynchronized cortical states, as previously described in 6-hydroxydopamine-lesioned rats. In contrast to toxin-based models, we found a small decrease, rather than an increase, in beta oscillations in the desynchronized state. Similarly, synchronized burst firing of nigral neurons observed in toxin-based models was not observed in ASO mice. Instead, we found more subtle changes in pauses of SNpr firing compared with wild-type control mice. Our results suggest that the pathophysiology underlying motor dysfunction in ASO mice is distinctly different from striatal dopamine-depletion models of parkinsonism.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Radoslav I Raychev ◽  
Jeffrey Saver ◽  
Scott Brown ◽  
Gary Duckwiler ◽  
Reza Jahan ◽  
...  

Background: Targeted eloquence-based tissue reperfusion within the primary motor cortex may have differential effect on disability as compared to the traditional volume-based (TICI) reperfusion after endovascular thrombectomy (EVT) in setting of acute ischemic stroke (AIS). Methods: We explored the impact of eloquent reperfusion (ER) within primary motor cortex (PMC) on clinical outcome (mRS) in AIS patients undergoing EVT. ER was defined as presence of flow on final digital subtraction angiography (DSA) within four main cortical branches, supplying the PMC (MCA - precentral, central, anterior parietal; ACA- pericallosal) and graded as absent (0), partial (1), and complete (2). Prospectively collected data from two centers were analyzed. Multivariable analysis was conducted to assess the impact of ER on 90-day disability (mRS) among patients with anterior circulation occlusion who achieved partial reperfusion (TICI 2 a and b). Results: Among the 125 patients who met study criteria, median age was 73, median NIHSS was 16, median ASPECTS was 7, 48% (60/125) were female, and 36.8% achieved functional independence (mRS 0-2) at 90 days. ER distribution was: Absent (0) in 19/125 (15.2%); Partial (1) in 52/125 (41.6%), and Complete (2) in 54/125 (43.2%). TICI 2b was achieved in 102/125 (81.6%) and ER was substantially higher in those patients (p<0.001). In multivariate analysis, in addition to age and sICH, ER had a profound independent impact on 90-day disability (OR 6.10, p=0.001 for ER 1 vs 0; and OR 9.87, p<0.001 for ER 2 vs 0). In contrast, extent of total partial reperfusion (TICI 2b vs 2a) was not related to 90-day disability. Conclusions: Our findings support that eloquent PMC-tissue reperfusion is a major determinant of functional outcome, more impactful than volume-based degree of partial reperfusion. More aggressive, PMC-targeted revascularization among patients with non-eloquent partial reperfusion may further improve post-stroke disability after EVT.


1997 ◽  
Vol 78 (3) ◽  
pp. 1516-1530 ◽  
Author(s):  
Ruth E. Martin ◽  
Gregory M. Murray ◽  
Pentti Kemppainen ◽  
Yuji Masuda ◽  
Barry J. Sessle

Martin, Ruth E., Gregory M. Murray, Pentti Kemppainen, Yuji Masuda, and Barry J. Sessle. Functional properties of neurons in the primate tongue primary motor cortex during swallowing. J. Neurophysiol. 78: 1516–1530, 1997. Recent studies conducted in our laboratory have suggested that the tongue primary motor cortex (i.e., tongue-MI) plays a critical role in the control of voluntary tongue movements in the primate. However, the possible involvement of tongue-MI in semiautomatic tongue movements, such as those in swallowing, remains unkown. Therefore the present study was undertakein in attempts to address whether tongue-MI plays a role in the semiautomatic tongue movements produced during swallowing. Extracellular single neuron recordings were obtained from tongue-MI, defined by intracortical microstimulation (ICMS), in two awake monkeys as they performed three types of swallowing (swallowing of a juice reward after successful tongue task performance, nontask-related swallowing of a liquid bolus, and nontask-related swallowing of a solid bolus) as well as a trained tongue-protrusion task. Electromyographic activity was recorded simultaneously from various orofacial and laryngeal muscles. In addition, the afferent input to each tongue-MI neuron and ICMS-evoked motor output characteristics at each neuronal recording site were determined. Neurons were considered to show swallow and/or tongue-protrusion task-related activity if a statistically significant difference in firing rate was seen in association with these behaviors compared with that observed during a control pretrial period. Of a total of 80 neurons recorded along 40 microelectrode penetrations in the ICMS-defined tongue-MI, 69% showed significant alterations of activity in relation to the swallowing of a juice reward, whereas 66% exhibited significant modulations of firing in association with performance of the trained tongue-protrusion task. Moreover, 48% showed significant alterations of firing in relation to both swallowing and the tongue-protrusion task. These findings suggest that the region of cortex involved in swallowing includes MI and that tongue-MI may play a role in the regulation of semiautomatic tongue movement, in addition to trained motor behavior. Swallow-related tongue-MI neurons exhibited a variety of swallow-related activity patterns and were distributed throughout the ICMS-defined tongue-MI at sites where ICMS evoked a variety of types of tongue movements. These findings are consistent with the view that multiple efferent zones for the production of tongue movements are activated in swallowing. Many swallow-related tongue-MI neurons had an orofacial mechanoreceptive field, particularly on the tongue dorsum, supporting the view that afferent inputs may be involved in the regulation of the swallowing synergy.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Desmond Agboada ◽  
Mohsen Mosayebi Samani ◽  
Asif Jamil ◽  
Min-Fang Kuo ◽  
Michael A. Nitsche

AbstractSize and duration of the neuroplastic effects of tDCS depend on stimulation parameters, including stimulation duration and intensity of current. The impact of stimulation parameters on physiological effects is partially non-linear. To improve the utility of this intervention, it is critical to gather information about the impact of stimulation duration and intensity on neuroplasticity, while expanding the parameter space to improve efficacy. Anodal tDCS of 1–3 mA current intensity was applied for 15–30 minutes to study motor cortex plasticity. Sixteen healthy right-handed non-smoking volunteers participated in 10 sessions (intensity-duration pairs) of stimulation in a randomized cross-over design. Transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEP) were recorded as outcome measures of tDCS effects until next evening after tDCS. All active stimulation conditions enhanced motor cortex excitability within the first 2 hours after stimulation. We observed no significant differences between the three stimulation intensities and durations on cortical excitability. A trend for larger cortical excitability enhancements was however observed for higher current intensities (1 vs 3 mA). These results add information about intensified tDCS protocols and suggest that the impact of anodal tDCS on neuroplasticity is relatively robust with respect to gradual alterations of stimulation intensity, and duration.


2008 ◽  
Vol 20 (1) ◽  
pp. 5-22 ◽  
Author(s):  
Bogdan Sadowski

Plasticity of the Cortical Motor SystemThe involvement of brain plastic mechanisms in the control of motor functions under normal and pathological conditions is described. These mechanisms are based on a similar principle as the neuronal models of neuronal plasticity - long-term potentiation (LTP), and long-term depression (LTD). In the motor cortex, LTP-like phenomena play a role in strengthening synaptic connections between pyramidal neurons. LTD is important for the elimination of unnecessary inputs to the cortex. The dynamic features of the primary motor cortex activity depend on particular neuronal interconnectivity within this area. The pyramidal cells send horizontal collaterals to adjacent subregions of the primary motor cortex, and so can either excite or inhibit remote pyramidal cells. These connections can expand or shrink depending on actual physiological demands, and play a role in skill learning.


2019 ◽  
Author(s):  
Jérémy Cousineau ◽  
Léa Lescouzères ◽  
Anne Taupignon ◽  
Lorena Delgado-Zabalza ◽  
Emmanuel Valjent ◽  
...  

AbstractDopamine (DA) plays a crucial role in the control of motor and higher cognitive functions such as learning, working memory and decision making. The primary motor cortex (M1), which is essential for motor control and the acquisition of motor skills, receives dopaminergic inputs in its superficial and deep layers from the midbrain. However, the precise action of DA and DA receptor subtypes on the cortical microcircuits of M1 remains poorly understood. The aim of this work was to investigate how DA, through the activation of D2 receptors (D2R), modulates the cellular and synaptic activity of M1 parvalbumin-expressing interneurons (PVINs) which are crucial to regulate the spike output of pyramidal neurons (PNs). By combining immunofluorescence, ex vivo electrophysiology, pharmacology and optogenetics approaches, we show that D2R activation increases neuronal excitability of PVINs and GABAergic synaptic transmission between PVINs and PNs in layer V of M1. Our data reveal a mechanism through which cortical DA modulates M1 microcircuitry and might participate in the acquisition of motor skills.Significance StatementPrimary motor cortex (M1), which is a region essential for motor control and the acquisition of motor skills, receives dopaminergic inputs from the midbrain. However, precise action of dopamine and its receptor subtypes on specific cell types in M1 remained poorly understood. Here, we demonstrate in M1 that dopamine D2 receptors (D2R) are present in parvalbumin interneurons (PVINs) and their activation increases the excitability of the PVINs, which are crucial to regulate the spike output of pyramidal neurons (PNs). Moreover the activation of the D2R facilitates the GABAergic synaptic transmission of those PVINs on layer V PNs. These results highlight how cortical dopamine modulates the functioning of M1 microcircuit which activity is disturbed in hypo- and hyperdopaminergic states.


2018 ◽  
Author(s):  
Gerard Derosiere ◽  
David Thura ◽  
Paul Cisek ◽  
Julie Duque

AbstractDecisions about actions typically involve a period of deliberation that ends with the commitment to a choice and the motor processes overtly expressing that choice. Previous studies have shown that neural activity in sensorimotor areas, including the primary motor cortex (M1), correlates with deliberation features during action selection. Yet, the causal contribution of these areas to the decision process remains unclear. Here, we investigated whether M1 determines choice commitment, or whether it simply reflects decision signals coming from upstream structures and instead mainly contributes to the motor processes that follow commitment. To do so, we tested the impact of a disruption of M1 activity, induced by continuous theta burst stimulation (cTBS), on the behavior of human subjects in (1) a simple reaction time (SRT) task allowing us to estimate the duration of the motor processes and (2) a modified version of the tokens task (Cisek et al., 2009), which allowed us to estimate subjects’ time of commitment as well as accuracy criterion. The efficiency of cTBS was attested by a reduction in motor evoked potential amplitudes following M1 disruption, as compared to those following a sham stimulation. Furthermore, M1 cTBS lengthened SRTs, indicating that motor processes were perturbed by the intervention. Importantly, all of the behavioral results in the tokens task were similar following M1 disruption and sham stimulation, suggesting that the contribution of M1 to the deliberation process is potentially negligible. Taken together, these findings favor the view that M1 contribution is downstream of the decision process.New and noteworthyDecisions between actions are ubiquitous in the animal realm. Deliberation during action choices entails changes in the activity of the sensorimotor areas controlling those actions, but the causal role of these areas is still often debated. Using continuous theta burst stimulation, we show that disrupting the primary motor cortex (M1) delays the motor processes that follow instructed commitment but does not alter volitional deliberation, suggesting that M1 contribution may be downstream of the decision process.


2001 ◽  
Vol 85 (2) ◽  
pp. 869-885 ◽  
Author(s):  
S. N. Baker ◽  
R. Spinks ◽  
A. Jackson ◽  
R. N. Lemon

Neural synchronization in the cortex, and its potential role in information coding, has attracted much recent attention. In this study, we have recorded long spike trains (mean, 33,000 spikes) simultaneously from multiple single neurons in the primary motor cortex (M1) of two conscious macaque monkeys performing a precision grip task. The task required the monkey to use its index finger and thumb to move two spring-loaded levers into a target, hold them there for 1 s, and release for a food reward. Synchrony was analyzed using a time-resolved cross-correlation method, normalized using an estimate of the instantaneous firing rate of the cell. This was shown to be more reliable than methods using trial-averaged firing rate. A total of 375 neurons was recorded from the M1 hand area; 235 were identified as pyramidal tract neurons. Synchrony was weak [mean k′ = 1.05 ± 0.04 (SD)] but widespread among pairs of M1 neurons (218/1359 pairs with above-chance synchrony), including output neurons. Synchrony usually took the form of a broad central peak [average width, 18.7 ± 8.7 (SD) ms]. There were marked changes during different phases of the task. As a population, synchrony was greatest during the steady hold period in striking contrast to the averaged cell firing rate, which was maximal when the animal was moving the levers into target. However, the modulation of synchrony during task performance showed considerable variation across individual cell pairs. Two types of synchrony were identified: oscillatory (with periodic side lobes in the cross-correlation) and nonoscillatory. Their relative contributions were quantified by filtering the cross-correlations to exclude either frequencies from 18 to 37 Hz or all higher and lower frequencies. At the peak of population synchrony during the hold period, about half (51.7% in one monkey, 56.2% in the other) of the synchronization was within this oscillatory bandwidth. This study provides strong support for assemblies of neurons being synchronized during specific phases of a complex task with potentially important consequences for both information processing within M1 and for the impact of M1 commands on target motoneurons.


Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Doris D Wang ◽  
Coralie de Hemptinne ◽  
Svjetlana Miocinovic ◽  
Witney Chen ◽  
Jill L Ostrem ◽  
...  

Abstract INTRODUCTION In Parkinson's disease, the emergence of motor dysfunction is thought to be related to an imbalance between antikinetic and prokinetic patterns of oscillatory activity in the motor network. Invasive recordings from the basal ganglia and cortex in surgical patients have suggested that levodopa and therapeutic deep brain stimulation can suppress antikinetic beta band (13-30 Hz) rhythms while promoting prokinetic gamma band (60-90 Hz) rhythms. Surgical ablation of the globus pallidus internus is one of the oldest effective therapies for Parkinson's disease and gives a remarkable immediate relief from rigidity and bradykinesia, but its effects on oscillatory activity in the motor network have not been studied. We characterize the effects of pallidotomy on cortical oscillatory activity in Parkinson's disease patients. METHODS Using a temporary 6-contact lead placed over the sensorimotor cortex in the subdural space, we recorded acute changes in cortical oscillatory activities in 3 Parkinson's disease patients undergoing pallidotomy and compared the results to that of 3 essential tremor patients undergoing thalamotomy. RESULTS In all 3 Parkinson's disease patients, we observed the emergence of an approximately 70 to 80 Hz narrow-band oscillation with effective thermolesion of the pallidum. This gamma oscillatory activity was spatially localized over the primary motor cortex, was minimally affected by voluntary movements, and was not found in the motor cortex of essential tremor patients undergoing thalamotomy. CONCLUSION Our finding suggests that acute lesioning of the pallidum promotes cortical gamma band oscillations. This may represent an important mechanism for alleviating bradykinesia in Parkinson's disease.


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