Alzheimer’s patients show reduced neural integration during brain stimulation

New research suggests that the electrical complexity of the brain diminishes in early Alzheimer’s disease, potentially signaling a breakdown in the neural networks that support conscious awareness. By stimulating the brain with magnetic pulses and recording the response, scientists found distinct differences between healthy aging adults and those with mild dementia. These findings appear online in the journal Neuroscience of Consciousness.

The human brain operates on multiple levels of awareness. Alzheimer’s disease is widely recognized for eroding memory, but the specific type of memory loss offers clues about the nature of the condition. Patients typically lose the ability to consciously recall events, facts, and conversations. This is known as explicit memory.

Yet, these same individuals often retain unconscious capabilities, such as the ability to walk, eat, or play a musical instrument. This preservation of procedural or implicit memory suggests that the disease targets the specific neural architecture required for conscious processing while leaving other automatic systems relatively intact.

Andrew E. Budson, a professor of neurology at Boston University Chobanian & Avedisian School of Medicine, has proposed that these “cortical dementias” should be viewed as disorders of consciousness. According to this theory, consciousness developed as part of the explicit memory system. As the disease damages the cerebral cortex, the physical machinery capable of sustaining complex conscious thought deteriorates. This deterioration eventually leads to a state where the individual is awake but possesses a diminishing capacity for complex awareness.

To investigate this theory, a research team led by Brenna Hagan, a doctoral candidate in behavioral neuroscience at the same institution, sought a biological marker that could quantify this decline. They turned to a metric originally developed to assess patients with severe brain injuries, such as those in comas or vegetative states. This metric is called the perturbation complexity index, specifically an analysis of state transitions.

The measurement acts somewhat like a sonar system for the brain. In a healthy, conscious brain, a stimulus should trigger a complex, long-lasting chain reaction of electrical activity that ripples across various neural networks. In a brain where consciousness is compromised, the response is expected to be simpler, local, and short-lived. The researchers hypothesized that even in the early stages of Alzheimer’s, this capacity for complex electrical integration would be reduced compared to healthy aging.

The study included 55 participants in total. The breakdown consisted of 28 individuals diagnosed with early-stage Alzheimer’s disease or mild cognitive impairment and 27 healthy older adults who served as controls. The research team employed a technique known as transcranial magnetic stimulation, or TMS, paired with electroencephalography, or EEG.

During the experiment, participants sat comfortably while wearing a cap fitted with 64 electrodes designed to detect electrical signals on the scalp. The researchers placed a magnetic coil against the participant’s head. This coil delivered a brief, focused pulse of magnetic energy through the skull and into the brain tissue. This pulse is the “perturbation” in the index’s name. It effectively rings the brain like a bell.

The researchers targeted two specific areas of the brain. The first was the left motor cortex, which controls voluntary movement on the right side of the body. The second was the left inferior parietal lobule, a region involved in integrating sensory information and language. By stimulating these distinct sites, the team hoped to determine if the loss of complexity was specific to certain areas or if it represented a global failure of the brain’s networks.

As the magnetic pulse struck the cortex, the EEG electrodes recorded the brain’s immediate reaction. This recording captured the “echo” of the stimulation as it propagated through the neural circuits. The researchers then used a complex mathematical algorithm to analyze these echoes. They looked for the number of “state transitions,” which are shifts in the spatial pattern of the electrical activity. A higher number of state transitions indicates a more complex, integrated response, implying a healthier and more connected brain.

The analysis revealed a clear distinction between the two groups. The participants with Alzheimer’s disease displayed a reduced level of brain complexity compared to the healthy controls. The average complexity score for the Alzheimer’s group was 20.1. In contrast, the healthy group averaged 28.2. This downward shift suggests that the neural infrastructure required for high-level conscious thought is compromised in the disease.

The reduction in complexity was consistent regardless of which brain area was stimulated. The scores obtained from the motor cortex were nearly identical to those from the parietal lobe. This suggests that the loss of neural complexity in Alzheimer’s is a widespread, global phenomenon rather than a problem isolated to specific regions. The disease appears to affect the brain’s overall ability to sustain complex patterns of communication.

The researchers also examined whether these complexity scores correlated with standard clinical measures. They compared the EEG data to scores from the Montreal Cognitive Assessment, a paper-and-pencil test commonly used to screen for dementia.

Within the groups, there was no strong statistical relationship between a person’s cognitive test score and their brain complexity score. This lack of correlation implies that the magnetic stimulation technique measures a fundamental physiological state of the brain that is distinct from behavioral performance on a test.

“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,” Budson explains. He adds that when patients leave familiar settings, “their home routines are not helpful and their dysfunctional conscious memory can lead to disorientation and distress.”

There are caveats to these findings that warrant attention. While the difference between the groups was clear, the absolute scores raised questions. A surprising number of participants in both groups scored below the threshold typically used to define consciousness in coma studies. Specifically, 70 percent of the Alzheimer’s patients and 29 percent of the healthy volunteers fell into a range usually associated with unconsciousness or minimally conscious states.

This does not mean these individuals are unconscious. Instead, it indicates that the mathematical cutoffs established for traumatic brain injury may not directly apply to neurodegenerative diseases or aging populations. The metric likely exists on a spectrum. The physiological changes in an aging brain might lower the baseline for complexity without extinguishing consciousness entirely.

The study opens new paths for future research. Scientists can now explore how this loss of complexity relates to the progression of the disease. It may be possible to use this metric to track the transition from mild impairment to severe dementia. The lack of correlation with behavioral tests suggests that this method could provide an objective, biological way to assess brain function that does not rely on a patient’s ability to speak or follow instructions.

This perspective also informs potential therapeutic strategies. If the disease is viewed as a progressive loss of conscious processing, treatments could focus on maximizing the use of preserved unconscious systems. Therapies might emphasize habit formation and procedural learning to help patients maintain independence.

“This research opens the avenue for future studies in individuals with cortical dementia to examine the relationship between conscious processes, global measures of consciousness, and their underlying neuroanatomical correlates,” Budson says. The team hopes that future work will clarify the biological mechanisms driving this loss of complexity and lead to better diagnostic tools.

The study, “Evaluating Alzheimer’s disease with the TMS-EEG perturbation complexity index,” was authored by Brenna Hagan, Stephanie S. Buss, Peter J. Fried, Mouhsin M. Shafi, Katherine W. Turk, Kathy Y. Xie, Brandon Frank, Brice Passera, Recep Ali Ozdemir, and Andrew E. Budson.