Signal Propagation and Its Relationship to Cognitive Performance in the Aging Human Brain (Focus or Spread)

Study Overview
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Brief Summary
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In the next three decades, the world's population over 60 years old is expected to more than double its size. Even in the absence of an obvious pathology (i.e., healthy aging), advancing age is typically associated with a progressive decline in cognitive performance. Although pathophysiological changes in age-related neurodegenerative disorders have received much attention over the past years, far less is known about the neural processes affecting cognition in healthy ageing. One of these postulated processes is neural dedifferentiation (i.e., a decrease in neural selectivity, by which neural representations of processed information become less univocally distinguishable), possibly accompanied by the recruitment of additional cortical areas in the healthy aging brain. To date, these processes have been extensively studied on the neural level, yet their functional significance for cognitive behaviour remains largely unclear. This project will investigate neural dedifferentiation and its relationship to cognitive performance in the healthy aging brain. To this end, the investigators will use a combination of state-of-the-art technologies including simultaneous transcranial magnetic stimulation (TMS) and high-density electroencephalography (hd-EEG) as well as diffusion tensor imaging (DTI). Perspectives include a better understanding of the relationship between neurophysiological mechanisms and cognitive performance in the healthy aging brain.

Official Title
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Better to Focus or to Spread? Signal Propagation and Its Relationship to Cognitive Performance in the Aging Human Brain

Conditions
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Healthy Aging

Intervention / Treatment
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* Device: single-puls TMS
* Device: sham stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent as documented by signature Age between 20-30 or 65-75 years Neurologically healthy, i.e., with no documented or present neurological disease or brain injury Normal or corrected-to-normal visual acuity Exclusion Criteria: Any instable medical condition, in particular epilepsy (past or present, including seizures or febrile convulsions) Any surgical intervention to the brain Heart diseases Implanted medical devices (e.g., cochlear implants, infusion pumps, neurostimulators, pacemakers) History of migraine or strong headaches Sleep deprivation Presence of non-MRI safe metal in the body Drug or alcohol abuse Intake of any medication that is likely to lower seizure threshold Claustrophobia For female participants: in order to participate in the study, female participants in reproductive age need to take a pregnancy test (a standard urine pregnancy test will be provided). For female participants: breastfeeding Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, etc. of the participant Lack of knowledge of the German language Participation in another study with investigational drug within the 30 days preceding and during the present study Previous enrolment into the current study Enrolment of the investigator, his/her family members, employees and other dependent persons

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy younger participants (20-30y)<br>Within-subject design. In a visual discrimination task participants will be asked to identify specific features of visual stimuli (i.e., the gender of a face, or the motion direction of a grating). During this task, single-pulse TMS will be applied in one-third of the trials; sham stimulation will be applied in a further third of the trials; and no stimulation will be applied in the remaining third of the trials, while hd-EEG will be continuously measured. The order of these three stimulation conditions (i.e., single-pulse TMS, sham, or no stimulation, during the 1st, 2nd, or 3rd third of the trials) will be counterbalanced over participants. | Device: single-puls TMS<br>* Medical Device (MD): MagPro X100<br>Device: sham stimulation<br>* Sham stimulation is delivered with a dedicated coil, which is magnetically shielded and thus produces only approx. 20% of the nominal magnetic field. This is not enough to reach and stimulate the cortex, but the produced sound and scalp sensation are the same as with a real TMS coil.<br>|
| Experimental: Healthy older participants (65-75y)<br>Within-subject design. In a visual discrimination task participants will be asked to identify specific features of visual stimuli (i.e., the gender of a face, or the motion direction of a grating). During this task, single-pulse TMS will be applied in one-third of the trials; sham stimulation will be applied in a further third of the trials; and no stimulation will be applied in the remaining third of the trials, while hd-EEG will be continuously measured. The order of these three stimulation conditions (i.e., single-pulse TMS, sham, or no stimulation, during the 1st, 2nd, or 3rd third of the trials) will be counterbalanced over participants. | Device: single-puls TMS<br>* Medical Device (MD): MagPro X100<br>Device: sham stimulation<br>* Sham stimulation is delivered with a dedicated coil, which is magnetically shielded and thus produces only approx. 20% of the nominal magnetic field. This is not enough to reach and stimulate the cortex, but the produced sound and scalp sensation are the same as with a real TMS coil.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Age-related differences in the spatio-temporal patterns of signal propagation | The spatiotemporal patterns of signal propagation, as measured with a combined TMS-hd-EEG approach, in younger and older healthy participants, reflecting age-related differences on the neural level. | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between the performance in a cognitive test battery and patterns of signal propagation in younger and older participants | The association between the performance in a specific cognitive test and the aforementioned patterns of signal propagation in younger and older healthy participants, reflecting the functional significance of these age-related patterns on the cognitive level. | 4 hours | 
| Association between the performance in a cognitive test battery and patterns of signal propagation in better- and worse-performers | The association between the performance in a specific cognitive test and the aforementioned patterns of signal propagation in better- and worse-performers, reflecting the functional significance of these age-independent patterns on the cognitive level. | 4 hours | 
| Association between the patterns of signal propagation and the structural properties of the white matter | The association between the aforementioned patterns of signal propagation and the structural properties of the white matter interconnecting the involved cortical areas, as measured by DTI. | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transcranial magnetic stimulation (TMS), high-density electroencephalography (hd-EEG), simultaneous TMS-hd-EEG, diffusion tensor imaging (DTI), neural dedifferentiation