Traumatic brain injury, neurobiology of aggression and antisocial behavior: from large-scale brain networks to anatomical and molecular substrates
- 1Institute of Translational Pharmacology, National Research Council of Italy (CNR)
- 2Department of Human Sciences, Università degli Studi Guglielmo Marconi
Abstract
Traumatic brain injury (TBI) triggers a dynamic pathological cascade that often culminates in chronic neuropsychiatric sequelae, such as reactive aggression and antisocial behavior. While these debilitating manifestations severely impair social reintegration and quality of life, their heterogeneous nature complicates clinical and forensic characterization. This review addresses this challenge through an integrated, multiscale framework that bridges macro-scale network desynchronization with micro-circuit pathology. We illustrate how the mechanical disruption of major white matter tracts decouples large-scale neurocognitive networks, leaving subcortical emotional anchors in a state of unmodulated hyper-reactivity stripped of prefrontal inhibitory control. The macroscopic untethering operates in synergy with localized cellular failures within specific amygdalar subnuclei, where chronic neuroinflammation, oxidative stress, and ascending neuromodulatory alterations durably shift the affective circuitry toward a hyperexcitable state. By mapping these dimensional neurobiological substrates directly onto the DSM-5-TR taxonomic framework, we spark a new neuroforensic debate regarding criminal responsibility, considering the boundaries of volitional control and the contemporary debate on free will in organically compromised patients. This translational perspective guides the evaluation of novel therapeutic strategies, shifting the paradigm away from non-specific pharmacological sedation toward personalized, state-dependent neuromodulation capable of exogenously restoring circuit synchrony and patient clinical outcomes.
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BibTeX
@article{berretta2026traumatic,
title = {{Traumatic brain injury, neurobiology of aggression and antisocial behavior: from large-scale brain networks to anatomical and molecular substrates}},
author = {Erica Berretta and Luigi Manni and Marzia Soligo},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1925482},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1925482/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Traumatic brain injury, neurobiology of aggression and antisocial behavior: from large-scale brain networks to anatomical and molecular substrates
AU - Erica Berretta
AU - Luigi Manni
AU - Marzia Soligo
PY - 2026
DA - 2026/10/14
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1925482
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1925482/full
AB - Traumatic brain injury (TBI) triggers a dynamic pathological cascade that often culminates in chronic neuropsychiatric sequelae, such as reactive aggression and antisocial behavior. While these debilitating manifestations severely impair social reintegration and quality of life, their heterogeneous nature complicates clinical and forensic characterization. This review addresses this challenge through an integrated, multiscale framework that bridges macro-scale network desynchronization with micro-circuit pathology. We illustrate how the mechanical disruption of major white matter tracts decouples large-scale neurocognitive networks, leaving subcortical emotional anchors in a state of unmodulated hyper-reactivity stripped of prefrontal inhibitory control. The macroscopic untethering operates in synergy with localized cellular failures within specific amygdalar subnuclei, where chronic neuroinflammation, oxidative stress, and ascending neuromodulatory alterations durably shift the affective circuitry toward a hyperexcitable state. By mapping these dimensional neurobiological substrates directly onto the DSM-5-TR taxonomic framework, we spark a new neuroforensic debate regarding criminal responsibility, considering the boundaries of volitional control and the contemporary debate on free will in organically compromised patients. This translational perspective guides the evaluation of novel therapeutic strategies, shifting the paradigm away from non-specific pharmacological sedation toward personalized, state-dependent neuromodulation capable of exogenously restoring circuit synchrony and patient clinical outcomes.
SN - 1663-9812
ER -