Hierarchical inference dysfunction in autism and Alzheimer's disease: A conceptual predictive-coding framework from hyper-precision to predictive collapse
Abstract
Autism spectrum disorder (ASD) and Alzheimer's disease (AD) are characterized by profound alterations in cortical circuit function, synaptic plasticity, and neuromodulatory regulation, leading to disrupted hierarchical integration of feedforward and feedback signaling. This review synthesizes evidence that these disorders represent opposing patterns of dysfunction within hierarchical cortical systems governing sensory integration and contextual modulation. Within a predictive coding framework, these alterations can be understood as disturbances in precision weighting, a process critically implemented by neuromodulatory systems. In ASD, neurodevelopmental alterations in excitatory-inhibitory balance, parvalbumin-positive interneuron function, laminar microcircuit organization, and neuromodulatory tuning bias cortical networks toward excessive bottom-up signaling and heightened synaptic gain, associated with increased gamma-band activity, local hyperconnectivity, and impaired contextual integration. In contrast, AD is marked by progressive degeneration of deep-layer pyramidal neurons, entorhinal-hippocampal circuits, and long-range feedback projections, together with cholinergic and dopaminergic depletion, disrupting beta- and alpha-mediated top-down coordination, impairing synaptic plasticity, and destabilizing large-scale networks such as the default mode system. Across the lifespan, these processes produce opposite distortions in hierarchical signal flow, namely…
Read the paper
Related studies
- Regulation of nucleolus assembly by non-coding RNA polymerase II transcripts
- For a Healthy Histone Code, a Little SUMO in the Tail Keeps the Acetyl Away
- Discovering a binary CTCF code with a little help from BORIS
- Article Commentary: Stabilizing the Code–-Methods to Preserve RNA Prove Their Worth
- Foreword to the Special Issue for the RINTC (The Implicit Seismic Risk of Code-Conforming Structures) Project
- Commentary: Promoting Health and Well-being in Pediatric Primary Care Settings: Using Health and Behavior Codes at Routine Well-child Visits
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.