Cortical propagation tracks functional recovery after stroke

Cecchini, Gloria; Scaglione, Alessandro; Mascaro, Anna Letizia Allegra; Checcucci, Curzio; Conti, Emilia; Adam, Ihusan; Fanelli, Duccio; Livi, Roberto; Pavone, Francesco S.; Kreuz, Thomas

doi:10.1371/journal.pcbi.1008963

Cited by 9 publications

(23 citation statements)

References 55 publications

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“…This is consistent with other studies that report widespread neuronal activity over the cortical mantle of animals engaged in behavioral tasks ( Allen et al, 2017 ; Steinmetz et al, 2019 ; Quarta et al, 2021 ). In particular, this is consistent with our previous findings where we observed a large wave traveling across most of the field of view especially during the reward pull ( Cecchini et al, 2021 ). Therefore the high degree of accuracy obtained for the detection of the pull for each parcel could be the expressions of traveling waves propagating over the cortex independently of the experimental group.…”

Section: Discussionsupporting

confidence: 93%

“…Finally, the separation among the three groups supports the idea that functional recovery is not necessarily entangled with the restoration of pre-stroke features of motor-related cortical activity. As mentioned in our previous works ( Cecchini et al, 2021 ; Conti et al, 2021b ), we believe that the rehabilitation paradigm can promote different strategies in order to overcome the structural and functional alterations induced by the stroke damage.…”

Section: Discussionmentioning

confidence: 80%

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Tracking the Effect of Therapy With Single-Trial Based Classification After Stroke

Scaglione

Conti

Mascaro

et al. 2022

Front. Syst. Neurosci.

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Stroke is a debilitating disease that leads, in the 50% of cases, to permanent motor or cognitive impairments. The effectiveness of therapies that promote recovery after stroke depends on indicators of the disease state that can measure the degree of recovery or predict treatment response or both. Here, we propose to use single-trial classification of task dependent neural activity to assess the disease state and track recovery after stroke. We tested this idea on calcium imaging data of the dorsal cortex of healthy, spontaneously recovered and rehabilitated mice while performing a forelimb retraction task. Results show that, at a single-trial level for the three experimental groups, neural activation during the reward pull can be detected with high accuracy with respect to the background activity in all cortical areas of the field of view and this activation is quite stable across trials and subjects of the same group. Moreover, single-trial responses during the reward pull can be used to discriminate between healthy and stroke subjects with areas closer to the injury site displaying higher discrimination capability than areas closer to this site. Finally, a classifier built to discriminate between controls and stroke at the single-trial level can be used to generate an index of the disease state, the therapeutic score, which is validated on the group of rehabilitated mice. In conclusion, task-related neural activity can be used as an indicator of disease state and track recovery without selecting a peculiar feature of the neural responses. This novel method can be used in both the development and assessment of different therapeutic strategies.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 80%

Tracking the Effect of Therapy With Single-Trial Based Classification After Stroke

Scaglione

Conti

Mascaro

et al. 2022

Front. Syst. Neurosci.

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“…These findings suggest that rehabilitation strategies for functional recovery might not essentially aim at the restoration of pre-stroke features of motor-related activity, as observed in a recent work by Cecchini and collaborators. 30 Nevertheless, the reestablishment of pre-stroke activation transients was a distinguished feature of the most efficient therapeutic approach, the combined therapy. In accordance with our previous findings 31 on a different combined rehabilitation paradigm, this study supports the hypothesis that the restoration of pre-stroke temporal features could be an important biomarker of the functional recovery.…”

Section: Discussionmentioning

confidence: 99%

Combining Optogenetic Stimulation and Motor Training Improves Functional Recovery and Perilesional Cortical Activity

Conti

Scaglione

Vito

et al. 2021

Neurorehabil Neural Repair

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Background. An ischemic stroke is followed by the remapping of motor representation and extensive changes in cortical excitability involving both hemispheres. Although stimulation of the ipsilesional motor cortex, especially when paired with motor training, facilitates plasticity and functional restoration, the remapping of motor representation of the single and combined treatments is largely unexplored. Objective. We investigated if spatio-temporal features of motor-related cortical activity and the new motor representations are related to the rehabilitative treatment or if they can be specifically associated to functional recovery. Methods. We designed a novel rehabilitative treatment that combines neuro-plasticizing intervention with motor training. In detail, optogenetic stimulation of peri-infarct excitatory neurons expressing Channelrhodopsin 2 was associated with daily motor training on a robotic device. The effectiveness of the combined therapy was compared with spontaneous recovery and with the single treatments (ie optogenetic stimulation or motor training). Results. We found that the extension and localization of the new motor representations are specific to the treatment, where most treatments promote segregation of the motor representation to the peri-infarct region. Interestingly, only the combined therapy promotes both the recovery of forelimb functionality and the rescue of spatio-temporal features of motor-related activity. Functional recovery results from a new excitatory/inhibitory balance between hemispheres as revealed by the augmented motor response flanked by the increased expression of parvalbumin positive neurons in the peri-infarct area. Conclusions. Our findings highlight that functional recovery and restoration of motor-related neuronal activity are not necessarily coupled during post-stroke recovery. Indeed the reestablishment of cortical activation features of calcium transient is distinctive of the most effective therapeutic approach, the combined therapy.

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“…This therapy already affects the central nervous system, whereby in addition to influencing vascular dementia, neuroregenerative and neuroprotective effects also appear to be in action [113]. A functional effect through the modulation of neural activity has already been shown in stroke models [114]. For the treatment of epilepsy, modulators of the T-type, Pand Q-type calcium channels are in clinical use-such as ethosuximide, pregabalin, and gabapentin.…”

Section: Voltage-dependent Calcium Channels Cause Spontaneous Oscillations In the Early Phase Of Cn Nsc Maturation And Allow Exogenous Inmentioning

confidence: 99%

Spontaneous Calcium Oscillations through Differentiation: A Calcium Imaging Analysis of Rat Cochlear Nucleus Neural Stem Cells

Voelker¹,

Voelker²,

Engert³

et al. 2021

Cells

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Causal therapies for the auditory-pathway and inner-ear diseases are still not yet available for clinical application. Regenerative medicine approaches are discussed and examined as possible therapy options. Neural stem cells could play a role in the regeneration of the auditory pathway. In recent years, neural stem and progenitor cells have been identified in the cochlear nucleus, the second nucleus of the auditory pathway. The current investigation aimed to analyze cell maturation concerning cellular calcium activity. Cochlear nuclei from PND9 CD rats were microscopically dissected and propagated as neurospheres in free-floating cultures in stem-cell medium (Neurobasal, B27, GlutaMAX, EGF, bFGF). After 30 days, the dissociation and plating of these cells took place under withdrawal of the growth factors and the addition of retinoic acid, which induces neural cell differentiation. Calcium imaging analysis with BAPTA-1/Oregon Green was carried out at different times during the differentiation phase. In addition, the influence of different voltage-dependent calcium channels was analyzed through the targeted application of inhibitors of the L-, N-, R- and T-type calcium channels. For this purpose, comparative examinations were performed on CN NSCs, and primary CN neurons. As the cells differentiated, a significant increase in spontaneous neuronal calcium activity was demonstrated. In the differentiation stage, specific frequencies of the spontaneous calcium oscillations were measured in different regions of the individual cells. Initially, the highest frequency of spontaneous calcium oscillations was ascertainable in the maturing somata. Over time, these were overtaken by calcium oscillations in the axons and dendrites. Additionally, in the area of the growth cones, an increasing activity was determined. By inhibiting voltage-dependent calcium channels, their expression and function in the differentiation process were confirmed. A comparable pattern of maturation of these channels was found in CN NSCs and primary CN neurons. The present results show that neural stem cells of the rat cochlear nucleus differentiated not only morphologically but also functionally. Spontaneous calcium activities are of great relevance in terms of neurogenesis and integration into existing neuronal structures. These functional aspects of neurogenesis within the auditory pathway could serve as future targets for the exogenous control of neuronal regeneration.

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Cortical propagation tracks functional recovery after stroke

Cited by 9 publications

References 55 publications

Tracking the Effect of Therapy With Single-Trial Based Classification After Stroke

Tracking the Effect of Therapy With Single-Trial Based Classification After Stroke

Combining Optogenetic Stimulation and Motor Training Improves Functional Recovery and Perilesional Cortical Activity

Spontaneous Calcium Oscillations through Differentiation: A Calcium Imaging Analysis of Rat Cochlear Nucleus Neural Stem Cells

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