Dorsolateral prefrontal cortex excitability assessed using TMS‐EEG and its relationship with neuropsychiatric symptoms in Alzheimer’s dementia
Bibliographic record
Abstract
Abstract Background Neuropsychiatric symptoms (NPS) are common in patients with Alzheimer’s Dementia (AD) and cause substantial distress to patients and caregivers. Mechanisms underlying NPS are not well known. Studies have found increased cortical excitability in patients with AD. Studies in other neuropsychiatric disorders have found increased cortical excitability in association with NPS. We hypothesized that cortical excitability will be negatively associated with cognition and positively associated with NPS in AD. Method This cross‐sectional study included participants diagnosed with probable AD using the NIA‐AA core clinical criteria. Cognition was assessed using Montreal Cognitive Assessment (MoCA) and NPS were assessed using the Neuropsychiatric Inventory‐Questionnaire (NPI‐Q). NPIQ agitation‐hyperactivity domain scores were calculated by combining scores on agitation, aggression, anxiety, disinhibition and irritability domains. Motor threshold and Transcranial Magnetic Stimulation (TMS) intensity sufficient to induce 1 millivolt (mV) peak to peak motor evoked potential were calculated as per established methods. TMS at the 1mV intensity was applied to the dorsolateral prefrontal cortex (DLPFC) at a frequency of 0.1 Hz. Electroencephalography was collected during TMS. Cortical excitability was assessed using rectified area under the curve (AUC) for TMS‐evoked potential (TEP) during early (25‐80 ms) and late phases (80 – 200 ms). Individual TEP peak amplitudes were also calculated. Result The study included 25 participants (female = 17, Mean (SD) age = 74.3(7.1) Years, Mean (SD) MoCA score = 17.5 (4.6)). There was a negative correlation between MoCA and the TEP early AUC at the DLPFC site of stimulation (Spearman’s rs = ‐ 0.589, n = 24, p = 0.002). In contrast there was a positive correlation between NPI‐Q agitation ‐ hyperactivity domain scores and the TEP early AUC (Spearman’s rs = 0.422, n = 24, p = 0.04). There was also a positive correlation between total NPIQ and early TEP (P30) amplitude. Conclusion Cortical excitability in the DLPFC is inversely associated with cognition and positively associated with NPS in AD. Specifically, increased excitability found during the early TEP duration suggests potential role of aberrant glutamatergic transmission and overall gamma amino butyric acid and glutamate imbalance. These findings may have important implications for developing treatment interventions targeting cortical excitability in AD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".