Amyloid induced hyperexcitability in default mode network drives medial temporal hyperactivity and early tau accumulation.
Joseph Giorgio, Jenna N. Adams, A. Maass, William J. Jagust, Michael Breakspear
Neuron December 1, 2023 DOI: 10.1016/j.neuron.2023.11.014 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Humans with early Alzheimer's disease |
| Topics | Default mode network |
| Key findings | Alzheimer's pathologies flip interactions between the default mode network and the medial temporal lobe from inhibitory to excitatory, with default mode network hyperexcitation predicting tau accumulation in the entorhinal cortex. |
Abstract
In early Alzheimer's disease (AD) β-amyloid (Aβ) deposits throughout association cortex and tau appears in the entorhinal cortex (EC). Why these initially appear in disparate locations is not understood. Using task-based fMRI and multimodal PET imaging, we assess the impact of local AD pathology on network-to-network interactions. We show that AD pathologies flip interactions between the default mode network (DMN) and the medial temporal lobe (MTL) from inhibitory to excitatory. The DMN is hyperexcited with increasing levels of Aβ, which drives hyperexcitability within the MTL and this directed hyperexcitation of the MTL by the DMN predicts the rate of tau accumulation within the EC. Our results support a model whereby Aβ induces disruptions to local excitatory-inhibitory balance in the DMN, driving hyperexcitability in the MTL, leading to tau accumulation. We propose that Aβ-induced disruptions to excitatory-inhibitory balance is a candidate causal route between Aβ and remote EC-tau accumulation.
Comparable studies
Other observational and cohort studies on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A default mode of brain function Normal adult human brain | 2001 | Observational study | |
| Resting-State Functional Connectivity Reflects Structural Connectivity in the Default Mode Network Healthy subjects | 2008 | Observational cohort | |
| Meditation experience is associated with increased cortical thickness Participants with extensive Insight meditation experience and matched controls | 2005 | Observational cohort | n = 20 |
| Meditation experience is associated with differences in default mode network activity and connectivity Experienced meditators and matched meditation-naive controls | 2011 | Observational cohort | |
| The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: Evidence from a partial correlation network analysis Healthy subjects | 2008 | Observational study |
Citations in the library
Cited by 2
Cites 3
- Modeling Ketamine Effects on Synaptic Plasticity During the Mismatch Negativity Cerebral Cortex August 8, 2012
- The Longitudinal Trajectory of Default Mode Network Connectivity in Healthy Older Adults Varies As a Function of Age and Is Associated with Changes in Episodic Memory and Processing Speed Journal of Neuroscience February 13, 2018
- Modulation of Effective Connectivity in the Default Mode Network at Rest and During a Memory Task Brain Connectivity February 1, 2015