November 16, 2022

Towards Personalized Precision Medicine for Stroke Recovery: A Multi‐Modal, Multidomain Longitudinal Approach (TiMeS)

1st Call, PM / PH Research

Short Summary

Stroke is the main course of long-term disability leaving more than 80% of patients with long-term deficits impacting on their daily professional and private life, health care systems and on society. Despite novel developments in neuro-rehabilitative therapy the outcome remains still unsatisfactory. Reasons for unsatisfactory recovery after are (i) stroke is a heterogenous disorder, (ii) insufficient understanding of processes relevant for recovery, (iii) lack of prediction of degree and course of recovery of individual patients and (iv) lack of patient-tailored personalized neuro-rehabilitative treatment to maximize individual treatment effects for patients. The current project will pave the way to the development of biomarkers, which allow to predict the individual degree and course of recovery as the basis for personalized precision medicine treatments. First approaches of precision rehabilitation based on neurotechnology (non-invasive brain stimulation, virtual reality and robotics) will be tested.

Goals

The current project addresses (1) the better, individual understanding of recovery and its underlying mechanisms by a multimodal, multi-domain, longitudinal evaluation of a large number of stroke patients, (2) the development of biomarkers usable in daily clinical life for stratification of patients towards precision medicine and (3) to apply first approaches of personalized neurotechnology-based neurorehabilitation. Such a project requires strong scientific and clinical expertise, up-to-date research equipment in close vicinity to large numbers of patients in the acute as well as in the subacute and chronic stage, requirements uniquely achieved in Sion. In summary, TiMeS will add to the better understanding of stroke and pave the way to novel, neurotechnology-based personalized treatment strategies.

Significance

TiMeS aims to acquire detailed multi-domain and multimodal information to understand mechanisms of recovery and to predict the course of recovery from the acute to the chronic phase after a stroke. This knowledge will translate into ‘biomarkers’, which can hopefully be used in daily clinical life and will impact on the selection of specific personalized treatments. The second main goal is to use the acquired understanding to develop and evaluate innovative, personalized interventional approaches based on neurotechnology, such as brain stimulation, virtual reality or robotics to maximize the interventional effects for each individual patient. If successful, this will significantly improve stroke neurorehabilitation with better outcomes for patients with respective impact on patients’ and relatives’ life, health care and socio-economics.

Background

In the global burden report, stroke has been described as the epidemic of the 21st century. This statement is based on the high incidence (e.g., 16.000 new patients/year in CH, 1.5 Million/year in Europe, 15 Millions/year in the world) with up to 20% of patients below 55 years. Despite current developments in stroke treatment, full recovery is still limited to 15-20%. This impacts daily life of the individual patients and their relatives and leads to significant cost for them and the society (29 Billion € in Europe). Remaining deficits of upper extremity function, especially hand function, is the main factor determining the re-integration into professional and social life, affecting independence and quality of life. Efforts in improving neuro-rehabilitative therapy remain unsatisfactory leaving still too many patients significantly impaired with a lack of independence and a need of continuous assistance from health care providers. What are the reasons for the still unsatisfactory recovery? Stroke is a heterogeneous disorder, there is insufficient understanding of the processes relevant for recovery, a lack of understanding of courses and degrees of recovery of the individual patients and an insufficient usage of the available rehabilitative treatment strategies (e.g., based on neuro-technologies), especially in the view of personalized, precision medicine. These facts lead to unsatisfactory treatment effects.

Publications

Bigoni C, Cadic-Melchior A., Vassiliadis P, Morishita T, Hummel FC (2022) An Automatized Method to Determine Latencies of Motor-Evoked Potentials under physiological and pathophysiological conditions. Journal of Neural Engineering Apr 2. doi: 10.1088/1741- 2552/ac636c. Online ahead of print. 20. Kinany N, Pirondini E, Mattera L, Martuzzi R, Micera S, Van De Ville D. (2022) Towards reliable spinal cord fMRI: Assessment of common imaging protocols. Apr 15;250:118964. doi: 10.1016/j.neuroimage.2022.118964.
Crema A, Bassolino M, Guanziroli E, Colombo M, Blanke O, Serino A, Micera S, & Molteni F (2022). Neuromuscular electrical stimulation restores upper limb sensory-motor functions and body representations in chronic stroke survivors. Med, 3(1), 58-74.e10.
Raffin E, Witon A, Salamanca-Giron RS, Huxlin K, Hummel FC (2021) Functional segregation within the dorsal frontoparietal network: a multimodal Dynamic Causal Modeling study. Cerebral Cortex Dec 1:bhab409. doi: 10.1093/cercor/bhab409. Online ahead of print.
Wessel MJ, Egger P, Hummel FC (2021) Predictive models for response to non-invasive brain stimulation in stroke: a critical review of opportunities and pitfalls. Brain Stimulation Sep 21;14(6):1456-1466. doi: 10.1016/j.brs.2021.09.006.
Fanciullacci C, Panarese A, Spina V, Lassi M, Mazzoni A, Artoni F, Micera S, Chisari C. Connectivity Measures Differentiate Cortical and Subcortical Sub- Acute Ischemic Stroke Patients. Front Hum Neurosci. 2021 Jul 1;15:669915.
Egger P*, Evangelista GG*, Koch PJ, Park CH, Levin-Gleba L, Girard G, Beanato E, Lee J, Choirat C, Guggisberg A, Kim YH, Hummel FC (2021) Disconnectomics of the rich club impacts motor recovery after stroke Stroke Jun;52(6):2115-2124. doi: 10.1161/STROKEAHA.120.031541. * contributed equally
Koch PJ, Park CH, Girard G, Beanato E, Egger P, Evangelista GG, Lee J, Koch G, Thiran J-P, Guggisberg A, Rosso C, Kim YH, Hummel FC (2021) The structural connectome and motor recovery after stroke: predicting natural recovery Brain Aug 17;144(7):2107-2119. doi: 10.1093/brain/awab082.
Wessel MJ, Park CH, Beanato E, Cuttaz EA, Timmermann JE, Schulz R, Morishita T, Koch PJ, Hummel FC (2021) Multifocal stimulation of the cerebro-cerebellar loop during the acquisition of a novel motor skill Nature Scientific Reports Jan 19;11(1):1756. doi: 10.1038/s41598-021- 81154-2.
Micera S, Calleo M, Chisari C., Hummel FC, Pedrocchi A (2020) Advanced neurotechnologies for the restoration of motor function Neuron 19;105(4):604-620
Kinany N, Pirondini E, Micera S, Van De Ville D. (2020) Dynamic Functional Connectivity of Resting-State Spinal Cord fMRI Reveals Fine-Grained Intrinsic Architecture. Neuron. Nov 11;108(3):424-435.e4. doi:10.1016/j.neuron.2020.07.024. Epub 2020 Sep 9. PMID: 32910894. 30. Pierella C, Pirondini E, Kinany N, Coscia M, Giang C, Miehlbradt J, Magnin C, Nicolo P, Dalise S, Sgherri G, Chisari C, Van De Ville D, Guggisberg A, Micera S. (2020) A multimodal approach to capture post-stroke temporal dynamics of recovery. J Neural Eng. Jul 10;17(4):045002. doi: 10.1088/1741-2552/ab9ada. PMID:32516757.
Giang C, Pirondini E, Kinany N, Pierella C, Panarese A, Coscia M, Miehlbradt J, Magnin C, Nicolo P, Guggisberg A, Micera S. (2020) Motor improvement estimation and task adaptation for personalized robot-aided therapy: a feasibility study. Biomed Eng Online. May 14;19(1):33.
Wessel MJ*,Draaisma LR*, De Boer A, Park CH, Maceira-Elvira P, Durand-Ruel M, Koch PJ, Morishita T, Hummel FC (2020) Cerebellar transcranial alternating current stimulation in the gamma range applied during the acquisition of a novel motor skill Nature Scientific Reports 10(1):11217 * contributed equally
Henneken T & Hummel FC (2020) Transkranielle elektrische Gleichstromstimulation (tDCS) zur Final Scientific Report 52 Behandlung des Schlaganfalls: Ein Update und ein Blick in die Zukunft Leading Opinions Neurologie & Psychiatrie 01/2019: 16-21.
Coscia M, Wessel MJ, Ujwal Chaudary, Millán JdR, Micera S, Guggisberg A, Vuadens P, Donoghue J, Birbaumer N*, Hummel FC* (2019) Neurotechnology-aided interventions for upper limb motor rehabilitation in severe chronic stroke Brain 142(8):2182-2197. doi: 10.1093/brain/awz181. * contributed equally.
Kinany N, Pirondini E, Martuzzi R, Mattera L, Micera S, Van de Ville D (2019) Functional imaging of rostrocaudal spinal activity during upper limb motor tasks. Neuroimage. Oct 15;200:590-600.
Guggisberg AG, Koch PJ Hummel FC, Buetefisch C (2019) Brain networks and their relevance for stroke rehabilitation Clin Neurophysiol. 130 (7): 1098-1124
Wessel MJ*, Draaisma LR*, Morishita T, Hummel FC (2019) The effects of stimulator, waveform, and current direction on intracortical inhibition and facilitation: a TMS comparison study Frontiers in Neuroscience 13:703. * contributed equally
Hummel FC (2018) Transkranielle elektrische Stimulation und ihre Bedeutung in der Neurorehabilitation, Neuroreha 10: 167–173 DOI : 10.1055/a-0754-3214
Crema A, Bassolino M, Guanziroli E, Colombo M, Blanke O, Serino A, Micera S, & Molteni F (2022). Neuromuscular electrical stimulation restores upper limb sensory-motor functions and body representations in chronic stroke survivors. Med, 3(1), 58-74.e10.
Egger P*, Evangelista GG*, Koch PJ, Park CH, Levin-Gleba L, Girard G, Beanato E, Lee J, Choirat C, Guggisberg A, Kim YH, Hummel FC (2021) Disconnectomics of the rich club impacts motor recovery after stroke Stroke Jun;52(6):2115-2124. doi: 10.1161/STROKEAHA.120.031541. * contributed equally
Micera S, Calleo M, Chisari C., Hummel FC, Pedrocchi A (2020) Advanced neurotechnologies for the restoration of motor function Neuron 19;105(4):604-620
Kinany N, Pirondini E, Micera S, Van De Ville D. (2020) Dynamic Functional Connectivity of Resting-State Spinal Cord fMRI Reveals Fine-Grained Intrinsic Architecture. Neuron. Nov 11;108(3):424-435.e4. doi:10.1016/j.neuron.2020.07.024. Epub 2020 Sep 9. PMID: 32910894.
Pierella C, Pirondini E, Kinany N, Coscia M, Giang C, Miehlbradt J, Magnin C, Nicolo P, Dalise S, Sgherri G, Chisari C, Van De Ville D, Guggisberg A, Micera S. (2020) A multimodal approach to capture post-stroke temporal dynamics of recovery. J Neural Eng. Jul 10;17(4):045002. doi: 10.1088/1741-2552/ab9ada. PMID:32516757
Coscia M, Wessel MJ, Ujwal Chaudary, Millán JdR, Micera S, Guggisberg A, Vuadens P, Donoghue J, Birbaumer N*, Hummel FC* (2019) Neurotechnology-aided interventions for upper limb motor rehabilitation in severe chronic stroke Brain 142(8):2182-2197. doi: 10.1093/brain/awz181. * contributed equally.
Kinany N, Pirondini E, Martuzzi R, Mattera L, Micera S, Van de Ville D (2019) Functional imaging of rostrocaudal spinal activity during upper limb motor tasks. Neuroimage. Oct 15;200:590-600.
Bigoni C, Zandvliet SB, Beanato E, Crema A, Coscia M, Espinsosa A, Henneken C, Oflar M, Hervé J, Evangelista G, Morishita T, Wessel MJ, Bonvin C, Turlan JL, Birbaumer N and Hummel FC (submitted) A novel patient-tailored, cumulative neurotechnology-based therapy for upper-limb rehabilitation in severely impaired chronic stroke patients: the AVANCER study.
Crema A, Bassolino M, Guanziroli E, Colombo M, Blanke O, Serino A, Micera S, & Molteni F (2022). Neuromuscular electrical stimulation restores upper limb sensory-motor functions and body representations in chronic stroke survivors. Med, 3(1), 58-74.e10.
Giang C, Pirondini E, Kinany N, Pierella C, Panarese A, Coscia M, Miehlbradt J, Magnin C, Nicolo P, Guggisberg A, Micera S. (2020) Motor improvement estimation and task adaptation for personalized robot-aided therapy: a feasibility study. Biomed Eng Online. May 14;19(1):33.
Kinany N, Pirondini E, Martuzzi R, Mattera L, Micera S, Van de Ville D (2019) Functional imaging of rostrocaudal spinal activity during upper limb motor tasks. Oct 15;200:590-600.
Hummel FC (2018) Transkranielle elektrische Stimulation und ihre Bedeutung in der Neurorehabilitation, Neuroreha 10: 167–173 DOI : 10.1055/a-0754-3214