Transcript Clinical Research Center for Brain Sciences, Herzog Hospital

Non invasive oscillatory stimulation treatment for combating late-life accelerated cognitive
decline
Preservation of cortical network synchronicity and
executive cognitive functions in prodromal
neurodegenerative dementia
Oded Meiron, Ph.D.
Head of Electrophysiology & Neurocognition lab at
Clinical Research Center for Brain Sciences, Herzog Hospital, Jerusalem
Overall Research goal: Inducing positive neurocognitive modulations in humans using
novel noninvasive brain stimulation treatments: normalizing electrophysiological
activity and enhancing cognition
Difference map of theta power (4–6 Hz) between conditions manipulation and retention during the entire delay period of 2000 ms is depicted.
Griesmayr et al., 2010 Neurobiology of Learning and behavior
In a pilot study(Meiron et al., in preparation): After examining 100 Healthy Adults ages 18 to90:
Natural age-related decay in prefrontal executive attention functioning: significant inverse association
between WM accuracy scores and age throughout the entire adult-life span (r = -.693, p < .001)
Douaud et al., 2014, PNAS
Douaud et al. (2014) using structura; MRI Identified an age related to whole Gray matter deterioration corresponding with
decline in executive attention function:
Spatially specific network of neocortical, limbic and paralimbic regions lateral prefrontal cortex, frontal eye field,
intraparietal sulcus, superior temporal sulcus, posterior cingulate cortex, and medial temporal lobe
showing monotonic decrease in whole gray matter from ages 40 to 90: associated with episodic memory deficits
Douaud et al., 2014, PNAS
Bihemispheric brain stimulation facilitates motor
recovery in chronic stroke patients (Lindenberg et al., 2010,
Neurology) :transcranial direct current stimulation(tDCS)
Datta et. al. Brain Stim 2009
Physiological Basis of Transcranial Direct Current Stimulation (Stagg
and Nitsche, 2011, Neuroscientist)
1)tDCS does indeed modulate synaptic strength within the cortex,
and evidence points to the involvement of intracortical neurons.
2) “excitatory (anodal) tDCS causes locally reduced GABA while
inhibitory (cathodal) stimulation causes reduced glutamatergic
neuronal activity with a highly correlated reduction in GABA”
(Stagg, 2009, Journal of Neuroscience)
Executive attention assessment: Verbal working memory performance (Meiron et al, 2013)
Normal cognitive ageing is associated with mild to moderate WM deficits
O. Meiron, M. Lavidor (2013) ; Brain Stimulation
Unilateral prefrontal direct current stimulation effects are modulated by working memory load and
gender
Illustration of online high-load WM accuracy enhancement
Meiron O, Lavidor M (2013): Bilateral Transcranial Alternating Current Stimulation (tACS) of the Dorsolateral Prefrontal Cortex
Enhances Verbal Working Memory and Promotes Episodic Memory After-effects. In Working Memory:
Promotes Episodic Memory After-effects
Meiron O, Lavidor M: Prefrontal oscillatory stimulation modulates access to cognitive control references in
retrospective metacognitive commentary. Clinical Neurophysiology 2014; 125:77-82
Using EEG, neurocognitive function, and personalized tACS protocols to
delay MCI and the onset of dementia: Alzheimer’s disease.
Evidence that ageing is related to lower resting EEG alpha power (i.e., amplitude of alpha).
An increase in resting theta power is not directly related to normal late-life ageing but more
likely a result of late-life neurological diseases (Klimesch, 1999, Finnigan and Robertson, 2011).
Recent data indicates that a decrease in induced theta amplitude occurs in progressive mild
cognitive impairment (MCI) patients versus stable-MCI patients and could be utilized as
biomarker of rapid cognitive decline (Deiber et al., 2009).
Distinct transcranial current frequencies (induced by tACS) might contribute to local excitability
in humans (Kirov et al., 2009, Zaehle, Rach and Herrmann, 2010, Schutter & Hortensius, 2010,
Meiron and Lavidor, 2013a,b), and may prove beneficial for delaying the onset of
neurodegenerative diseases such as progressive MCI and AD
Enabling Technology
•
Behaviorally-based electrophysiological biomedical device to denote the prognosis of
accelerated MCI symptoms versus normal ageing deficits
• Personalized tACS treatment to enhance and help maintain cognition and functional
capacity in normal ageing individuals and prodromal dementia patients, as well as
identifying and treating those with more pronounced neurocognitive deficits
Boggio et al.,, 2013
Transcranial direct current stimulation improves recognition memory in Alzheimer disease
Neurology August 12, 2008 vol. 71 no. 7 493-498 (Ferrucci et al)
Temporal-parietal cortex
Neuroenhancement of the Aging Brain: Restoring Skill Acquisition in Old Subjects
ANN NEUROL 2013;73:10–15(Zimerman et al, 2013)
Motor cortex
Envisioned product:
Designed to arrest or postpone pathological neurodegenerative ageing:
Innovative in its objective capability for early detection and prevention of accelerated cognitive decline in the ageing
population.
Discrepancies in taskrelated EEG oscillatory
cortical interactions
Identify functional EEG
frequencies that
correspond to optimal
executive attention
performance within a
certain age-range
Diagnose executive
attention deficits
Personalized repetitive
oscillatory electrical
stimulation treatment
protocols to preserve
adequate working
memory function and
delay possible progression
of MCI symptoms
Define performancerelated
electrophysiological
biomarkers of
premorbid accelerated
neurocognitive decline.
Thanks for listening
Special Thanks:
1) Mr. Lawrence Normie , Gerontech
2) Organizing Committee
3) Scientific Committee
3) Clinical Research Center for Brain Sciences, Herzog Hospital, Jerusalem