Emerging Theories of Allostatic-Interoceptive Overload in Neurodegeneration

Author: Daniel Franco-O'Byrne1,2, Hernando Santamaría-García3,4,5,6, Joaquín Migeot1,2, Agustín Ibáñez7,8,9,10,11
Affiliation: <sup>1</sup> Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibáñez, Santiago, Chile. <sup>2</sup> Center for Social and Cognitive Neuroscience (CSCN), School of Psychology, Universidad Adolfo Ibáñez, Santiago, Chile. <sup>3</sup> Global Brain Health Institute, University of California-San Francisco, San Francisco, CA, USA. <sup>4</sup> Trinity College Dublin, Dublin, Ireland. <sup>5</sup> Department of Psychiatry, Pontificia Universidad Javeriana, Bogotá, Colombia. <sup>6</sup> Center of Memory and Cognition Intellectus, Hospital Universitario San Ignacio, Bogotá, Colombia. <sup>7</sup> Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibáñez, Santiago, Chile. agustin.ibanez@gbhi.org. <sup>8</sup> Global Brain Health Institute, University of California-San Francisco, San Francisco, CA, USA. agustin.ibanez@gbhi.org. <sup>9</sup> Trinity College Dublin, Dublin, Ireland. agustin.ibanez@gbhi.org. <sup>10</sup> Cognitive Neuroscience Center (CNC), Universidad de San Andrés, Buenos Aires, Argentina. agustin.ibanez@gbhi.org. <sup>11</sup> Trinity College Institute of Neuroscience (TCIN), Trinity College Dublin, Dublin, Ireland. agustin.ibanez@gbhi.org.
Conference/Journal: Curr Top Behav Neurosci
Date published: 2024 Apr 19
Other: Special Notes: doi: 10.1007/7854_2024_471. , Word Count: 222


Recent integrative multilevel models offer novel insights into the etiology and course of neurodegenerative conditions. The predictive coding of allostatic-interoception theory posits that the brain adapts to environmental demands by modulating internal bodily signals through the allostatic-interoceptive system. Specifically, a domain-general allostatic-interoceptive network exerts adaptive physiological control by fine-tuning initial top-down predictions and bottom-up peripheral signaling. In this context, adequate adaptation implies the minimization of prediction errors thereby optimizing energy expenditure. Abnormalities in top-down interoceptive predictions or peripheral signaling can trigger allostatic overload states, ultimately leading to dysregulated interoceptive and bodily systems (endocrine, immunological, circulatory, etc.). In this context, environmental stress, social determinants of health, and harmful exposomes (i.e., the cumulative life-course exposition to different environmental stressors) may interact with physiological and genetic factors, dysregulating allostatic interoception and precipitating neurodegenerative processes. We review the allostatic-interoceptive overload framework across different neurodegenerative diseases, particularly in the behavioral variant frontotemporal dementia (bvFTD). We describe how concepts of allostasis and interoception could be integrated with principles of predictive coding to explain how the brain optimizes adaptive responses, while maintaining physiological stability through feedback loops with multiple organismic systems. Then, we introduce the model of allostatic-interoceptive overload of bvFTD and discuss its implications for the understanding of pathophysiological and neurocognitive abnormalities in multiple neurodegenerative conditions.

Keywords: Allostatic overload; Allostatic-interoceptive framework; Neurodegeneration; Predictive coding; bvFTD.

PMID: 38637414 DOI: 10.1007/7854_2024_471