Clinical trial NCT04361760: Signal Propagation and Its Relationship to Cognitive Performance in the Aging Human Brain (Focus or Spread)
Official title: Better to Focus or to Spread? Signal Propagation and Its Relationship to Cognitive Performance in the Aging Human Brain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Aging
Keywords: transcranial magnetic stimulation (TMS)
high-density electroencephalography (hd-EEG)
simultaneous TMS-hd-EEG
diffusion tensor imaging (DTI)
neural dedifferentiation
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2020-04-24
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Age-related differences in the spatio-temporal patterns of signal propagation
timeFrame: 2 hours
Secondary outcomes:
measure: Association between the performance in a cognitive test battery and patterns of signal propagation in younger and older participants
timeFrame: 4 hours
measure: Association between the performance in a cognitive test battery and patterns of signal propagation in better- and worse-performers
timeFrame: 4 hours
measure: Association between the patterns of signal propagation and the structural properties of the white matter
timeFrame: 4 hours
Other outcomes:
Locations:
city: Berne
country: Switzerland
facility: Department of Neurology, Inselspital, Bern University Hospital
Study officials:
affiliation: Department of Neurology, Inselspital, Bern University Hospital
name: René M. Müri, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Park J, Carp J, Kennedy KM, Rodrigue KM, Bischof GN, Huang CM, Rieck JR, Polk TA, Park DC. Neural broadening or neural attenuation? Investigating age-related dedifferentiation in the face network in a large lifespan sample. J Neurosci. 2012 Feb 8;32(6):2154-8. doi: 10.1523/JNEUROSCI.4494-11.2012.
citation: Sala-Llonch R, Bartres-Faz D, Junque C. Reorganization of brain networks in aging: a review of functional connectivity studies. Front Psychol. 2015 May 21;6:663. doi: 10.3389/fpsyg.2015.00663. eCollection 2015.
citation: Ziemann U. Transcranial magnetic stimulation at the interface with other techniques: a powerful tool for studying the human cortex. Neuroscientist. 2011 Aug;17(4):368-81. doi: 10.1177/1073858410390225. Epub 2011 Feb 10.
citation: Ozdemir RA, Tadayon E, Boucher P, Momi D, Karakhanyan KA, Fox MD, Halko MA, Pascual-Leone A, Shafi MM, Santarnecchi E. Individualized perturbation of the human connectome reveals reproducible biomarkers of network dynamics relevant to cognition. Proc Natl Acad Sci U S A. 2020 Apr 7;117(14):8115-8125. doi: 10.1073/pnas.1911240117. Epub 2020 Mar 19.