Abstract
An established method to assess effective brain connectivity is the combined use of transcranial magnetic stimulation with simultaneous electroencephalography (TMS–EEG) because TMS-induced cortical responses propagate to distant anatomically connected brain areas. Alzheimer’s disease (AD) and other dementias are associated with changes in brain networks and connectivity, but the underlying pathophysiology of these processes is poorly defined. We performed here a systematic review of the studies employing TMS–EEG co-registration in patients with dementias. TMS–EEG studies targeting the motor cortex have revealed a significantly reduced TMS-evoked P30 in AD patients in the temporo-parietal cortex ipsilateral to stimulation side as well as in the contralateral fronto-central area, and we have demonstrated a deep rearrangement of the sensorimotor system even in mild AD patients. TMS–EEG studies targeting other cortical areas showed alterations of effective dorsolateral prefrontal cortex connectivity as well as an inverse correlation between prefrontal-to-parietal connectivity and cognitive impairment. Moreover, TMS–EEG analysis showed a selective increase in precuneus neural activity. TMS–EEG co-registrations can also been used to investigate whether different drugs may affect cognitive functions in patients with dementias.
Highlights
The pathology related to Alzheimer’s disease (AD) leads to cortical large pyramidal neuron degeneration [1] with subsequent impairment of functional connectivity [2].In particular, amyloid-β (Aβ) plaques and tau-related neurofibrillary tangles have been found to be associated with focal synaptic disruption, which leads to regional brain structural changes, and to abnormal functional connectivity between anatomically distinct brain areas, neuronal circuits and pathways [3,4].Magnetic resonance imaging (MRI) and positron emission tomography have demonstrated important brain network changes in neurodegenerative diseases, including AD, but the underlying neurophysiological pathways driving pathological processes are still incompletely understood
We aimed to review here the transcranial magnetic stimulation with simultaneous electroencephalography (TMS–EEG) co-registration studies in patients with mild cognitive impairment (MCI), AD and other dementias
transcranial magnetic stimulation (TMS)-evoked response at around 30–50 ms was significantly reduced over widespread brain regions in AD patients
Summary
Amyloid-β (Aβ) plaques and tau-related neurofibrillary tangles have been found to be associated with focal synaptic disruption, which leads to regional brain structural changes, and to abnormal functional connectivity between anatomically distinct brain areas, neuronal circuits and pathways [3,4]. Magnetic resonance imaging (MRI) and positron emission tomography have demonstrated important brain network changes in neurodegenerative diseases, including AD, but the underlying neurophysiological pathways driving pathological processes are still incompletely understood. TMS may reveal local excitability changes in cortical and transcortical motor circuitries, while EEG and MEG are able to reveal cortical neural synchronization and connectivity with excellent temporal and spatial resolution. These novel approaches can help in detecting network disruption in neurodegenerative disease
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