MEG localization of a mPFC gating generator as a discrete (binary)
detector of AD at the
Several studies have shown that the pathological changes associated
with AD start years before the actual onset of clinical symptoms. This period
where the symptoms have not yet surfaced is called the preclinical stage of the
disease. By the time that the disease reaches the clinical stage, the
neurodegeneration is irreversible. This accounts for the failure to develop
‘Magnetoencephalography, a non-invasive brain imaging technique, used as a biomarker to detect Alzheimer’s disease even before onset of clinical symptoms.
Current state of the art diagnostic techniques has several
limitations, including lumbar puncture, time
constraints of scanning and exposure to radiation.
Josef Golubic found the location of the key - it was hidden in the topography
of auditory sensory gating network. She uncovered a topological biomarker of
preclinical and clinical AD pathology at the individual level that shows a
large effect size (0.98) and high accuracy, sensitivity and specificity (100%)
in identifying symptomatic AD patients within a research sample.
the present study, we demonstrate the use of the localization of neural sources
underlying neuromagnetic fields measured outside a head to detect AD even
before the onset of symptoms. The healthy controls activated a prefrontal
generator in response to both the deviant and repeating tones of an oddball
paradigm. To the contrary, the symptomatic AD group was lacking any medial
prefrontal gating generator activation to either the deviant or repeating tones.
However, we detected a sub-group of controls characterized by the absence of
prefrontal gating generator activation for the repeating tone only and
significantly lower scores on a mini-mental status exam and delayed visual
memory test - Rey-Osterreith Complex Figure Test. It is highly probable that
these individuals were captured in a preclinical AD phase since they show both
neuropsychological and neurophysiological impairments characteristic of an AD
type of dementia, although they did not yet meet clinical criteria for the
early phase of symptomatic AD"
Auditory Gating out Generator
Auditory gating out is a process by which one gets habituated to
redundant sounds preventing overload of information. Dysfunction of this gating
out mechanism or gating generator causes synaptic disturbances contributing to
the first symptoms of AD pathology.
The Study and its
MEG is a direct measure of neuronal activity is used as a biomarker
to localize the gating generator which is located in the medial prefrontal
cortex (mPFC), called the mPFC gating generator.
Using the oddball paradigm, two tones, standard and deviant were
played to the participants based on which the MEG localized the activity of the
mPFC gating generator.
- In healthy controls: mPFC generator
localized to both tones
- In symptomatic/clinical AD
(1) controls with mPFC generator localized in response to both the
standard and deviant tones; (2) a possible preclinical stage of AD participants
(a lower functioning group of controls) in which mPFC activation was localized
to the deviant tone only; and (3) symptomatic AD in which mPFC activation was
not localized to either the deviant or standard tones. References :
- Ideal biomarker' detects Alzheimer's disease before the onset of symptoms - (https://www.eurekalert.org/pub_releases/2017-10/afea-bd100217.php)
- Josef Golubic, S., Aine, C. J., Stephen, J. M., Adair, J. C., Knoefel, J. E. and Supek, S. (2017), MEG biomarker of Alzheimer's disease: Absence of a prefrontal generator during auditory sensory gating. Hum. Brain Mapp., 38: 5180-5194.doi:10.1002/hbm.23724