Boston University researchers say that a measure derived from electroencephalography (EEG) combined with transcranial magnetic stimulation (TMS) can distinguish people with Alzheimer’s disease (AD) from healthy older adults by detecting reduced brain response complexity. The study, published in the journal Neuroscience of Consciousness, that a measure that has been used to assess coma and minimally conscious states, called perturbation complexity index–state transitions (PCI-ST), is lower in individuals with AD, suggesting altered cortical network function related to impaired conscious cognitive processes. If further validated, the use of TMS-EEG to measured PCI-ST could become a quantitative biomarker that could be used to assess changes in consciousness and functional capacity in caused by AD.
“Despite their impaired conscious memory, individuals with Alzheimer’s disease may be able to use intact implicit, unconscious forms of memory, such as procedural memory (often termed ‘muscle memory’) to continue their daily routines at home, said senior author Andrew Budson, MD, a professor of neurology at BU’s Chobanian & Avedisian School of Medicine. “When they travel, however, their home routines are not helpful and their dysfunctional conscious memory can lead to disorientation and distress.”
The research focused on PCI-ST, which measures the complexity of the brain’s response to a brief TMS pulse delivered to the cortex. EEG captures how activity spreads across the scalp after stimulation, and PCI-ST quantifies the number of state transitions in these TMS-evoked potentials. A higher value indicates a richer pattern of causal interactions across brain networks, while lower values indicate reduced complexity.
To data, PCI-ST primarily has been used to determine levels of consciousness in coma and minimally conscious states. Prior research has established that it can identify people who are truly unconscious from those who retain covert awareness. The current study looked to leverage this measure to asses AD progressions, as conscious processes decline over time.
The reasoning behind this research comes from evidence that AD affects conscious awareness and higher cognitive functions, while some unconscious processes remain relatively spared. “As individuals with Alzheimer’s disease (AD) move from the mild cognitive impairment (MCI) stage to mild, moderate, and severe dementia, complex awareness deteriorates, although lower-level sensory awareness is relatively maintained,” the researchers noted. They added that unconscious processes such as procedural memory and priming may persist even as attention, working memory, episodic memory, and executive function decline.
To test whether PCI-ST is altered in AD, the team assessed 28 patients with AD and 27 healthy controls. Cognitive status was measured using the Montreal Cognitive Assessment, and disease severity was evaluated with the Clinical Dementia Rating scale. Participants underwent TMS-EEG with stimulation delivered to two cortical sites, the primary motor cortex and the inferior parietal lobule. PCI-ST values were then calculated from the EEG responses.
The results showed lower PCI-ST values in the AD group compared with controls regardless of the stimulation site. Mean PCI-ST was 20.1 in the AD group and 28.2 in healthy controls. According to the researchers, this pattern “suggests that PCIST may reflect the impaired conscious cognitive processes and functional capacity seen in AD.” The similarity of findings across stimulation sites indicated that PCI-ST reflects global network-level dysfunction rather than isolated regional changes in the brain.
The study also found broad variation in PCI-ST scores within both the AD and healthy control group, with no consistent associations between PCI-ST and standard measures of cognitive severity after accounting for group differences, an important finding that suggests PCI-ST can capture areas of neural dysfunction that are not measured by current behavioral assessments.
The findings could have future implications for diagnosis and care of people with AD. In advanced dementia, clinicians often rely on behavioral observation to judge awareness. A physiological measure of cortical response complexity could complement these observations, particularly in earlier stages of disease. Budson noted that treatments may either target conscious cognitive processes or leverage preserved unconscious memory systems. There is also the possibility that new pharmacologic interventions and non-pharmacological interventions could improve aspects of conscious function or quality of life.
Next steps for the team include standardizing TMS-EEG processing methods and examining how PCI-ST relates to disease progression, amyloid and tau pathology, and other neurodegenerative conditions. “Future studies will be needed to determine if PCIST can be used as a marker of conscious awareness in individuals with AD as they progress into the severe stage of dementia,” the researchers wrote.
