The influence of methylphenidate on heart rate and brain connectivity

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dc.contributor.advisorRauch, Laurieen_ZA
dc.contributor.advisorStein, Dan Jen_ZA
dc.contributor.advisorKing, Michaelen_ZA
dc.contributor.advisorJankiewicz, Marcinen_ZA
dc.contributor.authorVan Breda, Keelynen_ZA
dc.date.accessioned2018-04-24T13:50:00Z
dc.date.available2018-04-24T13:50:00Z
dc.date.issued2018en_ZA
dc.description.abstractThe central governor model (CGM) proposes that muscle recruitment is regulated by the brain through subconscious homeostatic control of afferent feedback. It has been suggested that the dopaminergic system plays a key role in the CGM, with dopaminergic activation leading to lower fatigue thresholds. Key neural circuits, including the central autonomic network (CAN), may also play a role in altering thresholds by reducing conscious bodily awareness, known as interoception. However, few studies have directly examined the dopaminergic neurotransmitter system and CAN connectivity, during exercise-induced fatigue. Although there is reason to suspect that subjects with high activity (HA) and low activity (LA) levels have different fatigue thresholds, potential differences in dopaminergic function and related circuity have not been compared across these groups. In this thesis, I was therefore interested in examining the impact of a dopaminergic agent, methylphenidate (MPH) on: a) brain connectivity at rest before exercise and during exercise, b) on heart rate (HR) at rest before exercise and during exercise. Furthermore, c) I was interested in whether the effect of MPH administration (MA) on HR and functional connectivity (FC), between CAN regions, pre-exercise impacted HR and FC during exercise and whether this differed between HA and LA subjects. In order to measure the effect of MA on brain connectivity at rest and during exercise I used a functional magnetic resonance imaging (fMRI) scanner. To measure the effect of MA on fatigue thresholds, I used a MRI compatible handgrip device which recorded grip force output during a fatiguing handgrip task. To measure HR before and during handgrip exercise I used a MRI compatible electrocardiogram (ECG) machine. My first study aimed to determine the effect of MA on resting state (R-fMRI) FC between CAN regions and its correlation with HR before exercise. My second study aimed to see the effect of MA on task HR, force output and, FC and EC between CAN regions, during a fatiguing handgrip task. My third study aimed to see the effect of MA on the relationship between HR and FC pre-exercise and HR and FC during exercise and whether this differed between LA and HA subjects. I found that: 1.) MA decreased R-fMRI FC between CAN regions, and that this was associated with an increase in HR during resting state 2.) MA decreased FC between CAN regions with an associated increase in task HR and force output during a fatiguing handgrip task 3.) After MA, R-fMRI FC determines task FC independent of HR 4.) MA significantly increased task HR in LA but not HA subjects 5.) After MA, R-fMRI FC determines task FC independent of HR in LA but not HA subjects. Taken together, the functional uncoupling of CAN regions and increased HR after MA suggests that MA increases the fatigue threshold by diverting attention away from interoceptive cues, such as HR. However, this finding may be more relevant in LA subjects, where MA is also associated with increased HR during exercise.en_ZA
dc.identifier.apacitationVan Breda, K. (2018). <i>The influence of methylphenidate on heart rate and brain connectivity</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,MRC/UCT RU for Exercise and Sport Medicine. Retrieved from http://hdl.handle.net/11427/27818en_ZA
dc.identifier.chicagocitationVan Breda, Keelyn. <i>"The influence of methylphenidate on heart rate and brain connectivity."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,MRC/UCT RU for Exercise and Sport Medicine, 2018. http://hdl.handle.net/11427/27818en_ZA
dc.identifier.citationVan Breda, K. 2018. The influence of methylphenidate on heart rate and brain connectivity. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Van Breda, Keelyn AB - The central governor model (CGM) proposes that muscle recruitment is regulated by the brain through subconscious homeostatic control of afferent feedback. It has been suggested that the dopaminergic system plays a key role in the CGM, with dopaminergic activation leading to lower fatigue thresholds. Key neural circuits, including the central autonomic network (CAN), may also play a role in altering thresholds by reducing conscious bodily awareness, known as interoception. However, few studies have directly examined the dopaminergic neurotransmitter system and CAN connectivity, during exercise-induced fatigue. Although there is reason to suspect that subjects with high activity (HA) and low activity (LA) levels have different fatigue thresholds, potential differences in dopaminergic function and related circuity have not been compared across these groups. In this thesis, I was therefore interested in examining the impact of a dopaminergic agent, methylphenidate (MPH) on: a) brain connectivity at rest before exercise and during exercise, b) on heart rate (HR) at rest before exercise and during exercise. Furthermore, c) I was interested in whether the effect of MPH administration (MA) on HR and functional connectivity (FC), between CAN regions, pre-exercise impacted HR and FC during exercise and whether this differed between HA and LA subjects. In order to measure the effect of MA on brain connectivity at rest and during exercise I used a functional magnetic resonance imaging (fMRI) scanner. To measure the effect of MA on fatigue thresholds, I used a MRI compatible handgrip device which recorded grip force output during a fatiguing handgrip task. To measure HR before and during handgrip exercise I used a MRI compatible electrocardiogram (ECG) machine. My first study aimed to determine the effect of MA on resting state (R-fMRI) FC between CAN regions and its correlation with HR before exercise. My second study aimed to see the effect of MA on task HR, force output and, FC and EC between CAN regions, during a fatiguing handgrip task. My third study aimed to see the effect of MA on the relationship between HR and FC pre-exercise and HR and FC during exercise and whether this differed between LA and HA subjects. I found that: 1.) MA decreased R-fMRI FC between CAN regions, and that this was associated with an increase in HR during resting state 2.) MA decreased FC between CAN regions with an associated increase in task HR and force output during a fatiguing handgrip task 3.) After MA, R-fMRI FC determines task FC independent of HR 4.) MA significantly increased task HR in LA but not HA subjects 5.) After MA, R-fMRI FC determines task FC independent of HR in LA but not HA subjects. Taken together, the functional uncoupling of CAN regions and increased HR after MA suggests that MA increases the fatigue threshold by diverting attention away from interoceptive cues, such as HR. However, this finding may be more relevant in LA subjects, where MA is also associated with increased HR during exercise. DA - 2018 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2018 T1 - The influence of methylphenidate on heart rate and brain connectivity TI - The influence of methylphenidate on heart rate and brain connectivity UR - http://hdl.handle.net/11427/27818 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/27818
dc.identifier.vancouvercitationVan Breda K. The influence of methylphenidate on heart rate and brain connectivity. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,MRC/UCT RU for Exercise and Sport Medicine, 2018 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/27818en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentMRC/UCT RU for Exercise and Sport Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherExercise Scienceen_ZA
dc.titleThe influence of methylphenidate on heart rate and brain connectivityen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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