Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson’s disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study
Background and objectivesIntermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive therapeutic option to alleviate the emergence of clinical deficits in Parkinson’s disease (PD) patients. Alth...
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1258315/full |
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| author | Raúl Rashid-López Raúl Rashid-López Paloma Macías-García Paloma Macías-García F. Luis Sánchez-Fernández F. Luis Sánchez-Fernández Fátima Cano-Cano Esteban Sarrias-Arrabal Esteban Sarrias-Arrabal Florencia Sanmartino Florencia Sanmartino Constantino Méndez-Bértolo Constantino Méndez-Bértolo Elena Lozano-Soto Elena Lozano-Soto Remedios Gutiérrez-Cortés Álvaro González-Moraleda Álvaro González-Moraleda Lucía Forero Lucía Forero Fernando López-Sosa Fernando López-Sosa Amaya Zuazo Rocío Gómez-Molinero Jaime Gómez-Ramírez José Paz-Expósito Guillermo Rubio-Esteban Raúl Espinosa-Rosso Raúl Espinosa-Rosso Álvaro J. Cruz-Gómez Álvaro J. Cruz-Gómez Javier J. González-Rosa Javier J. González-Rosa |
| author_facet | Raúl Rashid-López Raúl Rashid-López Paloma Macías-García Paloma Macías-García F. Luis Sánchez-Fernández F. Luis Sánchez-Fernández Fátima Cano-Cano Esteban Sarrias-Arrabal Esteban Sarrias-Arrabal Florencia Sanmartino Florencia Sanmartino Constantino Méndez-Bértolo Constantino Méndez-Bértolo Elena Lozano-Soto Elena Lozano-Soto Remedios Gutiérrez-Cortés Álvaro González-Moraleda Álvaro González-Moraleda Lucía Forero Lucía Forero Fernando López-Sosa Fernando López-Sosa Amaya Zuazo Rocío Gómez-Molinero Jaime Gómez-Ramírez José Paz-Expósito Guillermo Rubio-Esteban Raúl Espinosa-Rosso Raúl Espinosa-Rosso Álvaro J. Cruz-Gómez Álvaro J. Cruz-Gómez Javier J. González-Rosa Javier J. González-Rosa |
| author_sort | Raúl Rashid-López |
| collection | DOAJ |
| description | Background and objectivesIntermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive therapeutic option to alleviate the emergence of clinical deficits in Parkinson’s disease (PD) patients. Although it has been demonstrated that iTBS influences dopamine-dependent corticostriatal plasticity, little research has examined the neurobiological mechanisms underlying iTBS-induced clinical enhancement. Here, our primary goal is to verify whether iTBS bilaterally delivered over the primary motor cortex (M1) is effective as an add-on treatment at reducing scores for both motor functional impairment and nonmotor symptoms in PD. We hypothesize that these clinical improvements following bilateral M1-iTBS could be driven by endogenous dopamine release, which may rebalance cortical excitability and restore compensatory striatal volume changes, resulting in increased striato-cortico-cerebellar functional connectivity and positively impacting neuroglia and neuroplasticity.MethodsA total of 24 PD patients will be assessed in a randomized, double-blind, sham-controlled crossover study involving the application of iTBS over the bilateral M1 (M1 iTBS). Patients on medication will be randomly assigned to receive real iTBS or control (sham) stimulation and will undergo 5 consecutive sessions (5 days) of iTBS over the bilateral M1 separated by a 3-month washout period. Motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment; evaluation of M1 excitability; combined structural magnetic resonance imaging (MRI), resting-state electroencephalography and functional MRI; and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS.DiscussionThe findings of this study will help to clarify the efficiency of M1 iTBS for the treatment of PD and further provide specific neurobiological insights into improvements in motor and nonmotor symptoms in these patients. This novel project aims to yield more detailed structural and functional brain evaluations than previous studies while using a noninvasive approach, with the potential to identify prognostic neuroprotective biomarkers and elucidate the structural and functional mechanisms of M1 iTBS-induced plasticity in the cortico-basal ganglia circuitry. Our approach may significantly optimize neuromodulation paradigms to ensure state-of-the-art and scalable rehabilitative treatment to alleviate motor and nonmotor symptoms of PD. |
| first_indexed | 2024-03-11T19:49:56Z |
| format | Article |
| id | doaj.art-f356f41816cd4ac49c90bbd77594dee3 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-03-11T19:49:56Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-f356f41816cd4ac49c90bbd77594dee32023-10-05T12:01:52ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652023-10-011510.3389/fnagi.2023.12583151258315Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson’s disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial studyRaúl Rashid-López0Raúl Rashid-López1Paloma Macías-García2Paloma Macías-García3F. Luis Sánchez-Fernández4F. Luis Sánchez-Fernández5Fátima Cano-Cano6Esteban Sarrias-Arrabal7Esteban Sarrias-Arrabal8Florencia Sanmartino9Florencia Sanmartino10Constantino Méndez-Bértolo11Constantino Méndez-Bértolo12Elena Lozano-Soto13Elena Lozano-Soto14Remedios Gutiérrez-Cortés15Álvaro González-Moraleda16Álvaro González-Moraleda17Lucía Forero18Lucía Forero19Fernando López-Sosa20Fernando López-Sosa21Amaya Zuazo22Rocío Gómez-Molinero23Jaime Gómez-Ramírez24José Paz-Expósito25Guillermo Rubio-Esteban26Raúl Espinosa-Rosso27Raúl Espinosa-Rosso28Álvaro J. Cruz-Gómez29Álvaro J. Cruz-Gómez30Javier J. González-Rosa31Javier J. González-Rosa32Psychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainDepartment of Neurology, Puerta del Mar University Hospital, Cadiz, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainDepartment of Psychology, University of Cadiz, Cádiz, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainDepartment of Psychology, University of Cadiz, Cádiz, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainDepartment of Psychology, University of Cadiz, Cádiz, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainDepartment of Psychology, University of Cadiz, Cádiz, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainDepartment of Psychology, University of Cadiz, Cádiz, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainDepartment of Psychology, University of Cadiz, Cádiz, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainDepartment of Psychology, University of Cadiz, Cádiz, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainDepartment of Neurology, Puerta del Mar University Hospital, Cadiz, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainDepartment of Psychology, University of Cadiz, Cádiz, SpainDepartment of Radiodiagnostic and Medical Imaging, Puerta del Mar University Hospital, Cadiz, SpainDepartment of Psychology, University of Cadiz, Cádiz, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainDepartment of Radiodiagnostic and Medical Imaging, Puerta del Mar University Hospital, Cadiz, SpainDepartment of Neurology, Puerta del Mar University Hospital, Cadiz, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainDepartment of Neurology, Jerez de la Frontera University Hospital, Jerez de la Frontera, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainDepartment of Psychology, University of Cadiz, Cádiz, SpainPsychophysiology and Neuroimaging Group, Institute of Biomedical Research Cadiz (INiBICA), Cadiz, SpainDepartment of Psychology, University of Cadiz, Cádiz, SpainBackground and objectivesIntermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive therapeutic option to alleviate the emergence of clinical deficits in Parkinson’s disease (PD) patients. Although it has been demonstrated that iTBS influences dopamine-dependent corticostriatal plasticity, little research has examined the neurobiological mechanisms underlying iTBS-induced clinical enhancement. Here, our primary goal is to verify whether iTBS bilaterally delivered over the primary motor cortex (M1) is effective as an add-on treatment at reducing scores for both motor functional impairment and nonmotor symptoms in PD. We hypothesize that these clinical improvements following bilateral M1-iTBS could be driven by endogenous dopamine release, which may rebalance cortical excitability and restore compensatory striatal volume changes, resulting in increased striato-cortico-cerebellar functional connectivity and positively impacting neuroglia and neuroplasticity.MethodsA total of 24 PD patients will be assessed in a randomized, double-blind, sham-controlled crossover study involving the application of iTBS over the bilateral M1 (M1 iTBS). Patients on medication will be randomly assigned to receive real iTBS or control (sham) stimulation and will undergo 5 consecutive sessions (5 days) of iTBS over the bilateral M1 separated by a 3-month washout period. Motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment; evaluation of M1 excitability; combined structural magnetic resonance imaging (MRI), resting-state electroencephalography and functional MRI; and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS.DiscussionThe findings of this study will help to clarify the efficiency of M1 iTBS for the treatment of PD and further provide specific neurobiological insights into improvements in motor and nonmotor symptoms in these patients. This novel project aims to yield more detailed structural and functional brain evaluations than previous studies while using a noninvasive approach, with the potential to identify prognostic neuroprotective biomarkers and elucidate the structural and functional mechanisms of M1 iTBS-induced plasticity in the cortico-basal ganglia circuitry. Our approach may significantly optimize neuromodulation paradigms to ensure state-of-the-art and scalable rehabilitative treatment to alleviate motor and nonmotor symptoms of PD.https://www.frontiersin.org/articles/10.3389/fnagi.2023.1258315/fullParkinson’s diseasemotor and nonmotor symptomstranscranial magnetic stimulationintermittent theta-burst stimulationstructural magnetic resonance imagingfunctional connectivity |
| spellingShingle | Raúl Rashid-López Raúl Rashid-López Paloma Macías-García Paloma Macías-García F. Luis Sánchez-Fernández F. Luis Sánchez-Fernández Fátima Cano-Cano Esteban Sarrias-Arrabal Esteban Sarrias-Arrabal Florencia Sanmartino Florencia Sanmartino Constantino Méndez-Bértolo Constantino Méndez-Bértolo Elena Lozano-Soto Elena Lozano-Soto Remedios Gutiérrez-Cortés Álvaro González-Moraleda Álvaro González-Moraleda Lucía Forero Lucía Forero Fernando López-Sosa Fernando López-Sosa Amaya Zuazo Rocío Gómez-Molinero Jaime Gómez-Ramírez José Paz-Expósito Guillermo Rubio-Esteban Raúl Espinosa-Rosso Raúl Espinosa-Rosso Álvaro J. Cruz-Gómez Álvaro J. Cruz-Gómez Javier J. González-Rosa Javier J. González-Rosa Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson’s disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study Frontiers in Aging Neuroscience Parkinson’s disease motor and nonmotor symptoms transcranial magnetic stimulation intermittent theta-burst stimulation structural magnetic resonance imaging functional connectivity |
| title | Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson’s disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study |
| title_full | Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson’s disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study |
| title_fullStr | Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson’s disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study |
| title_full_unstemmed | Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson’s disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study |
| title_short | Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson’s disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study |
| title_sort | neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in parkinson s disease patients treated by intermittent theta burst stimulation over the bilateral primary motor area a randomized double blind sham controlled crossover trial study |
| topic | Parkinson’s disease motor and nonmotor symptoms transcranial magnetic stimulation intermittent theta-burst stimulation structural magnetic resonance imaging functional connectivity |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1258315/full |
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