Krieger Donald, Shepard Paul, Kontos Anthony, Collins Michael W, Puccio Ava, Eagle Shawn R, Schneider Walter, Okonkwo David O
Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, United States.
Department of Physics and Astronomy, University of Pittsburgh, PA, United States.
Front Neurol. 2025 Apr 30;16:1547786. doi: 10.3389/fneur.2025.1547786. eCollection 2025.
Every time a person sustains a blow to the head, they receive multiple atypical sensory inputs, often including pain. These directly stimulate the central nervous system. Yet, sensory input as a causal agent of neurophysiological dysfunction and post-concussion symptoms has never been explored. A new theory is proposed of sensory driven neurophysiological mechanisms of concussion (i) which are causally linked to the momentary blow to the head, (ii) whose time courses and other properties correspond to those observed to date for acute, sub-acute, and chronic symptoms, and (iii) which give rise to testable questions with experimentally measurable consequences. The primary assertion of the theory is that trauma induced excitation of key brain regions including the salience network (SN) and locus coeruleus (LC) can produce persistent dysfunctional alterations in the stable patterns of network excitability on which symptom-free neurological function depends. This mechanism is in play with any physical trauma, with or without a blow to the head. That is because atypical, painful, and otherwise high intensity sensory stimuli excite the SN and thence the LC, inducing plasticity widely in the brain. Many of those sensory stimuli may persist through the recovery period and while the brain is plastic, enable one or another network to learn altered and potentially dysfunctional patterns of network excitability. The secondary assertion of the theory is that with a blow to the head, convergence of high-intensity sensory stimuli within the brainstem and midbrain can cause neurophysiological coupling between brainstem nuclei which normally function independently, i.e. brainstem crosstalk (BCT). It is BCT which causes the signs and symptoms specific to head trauma, e.g., loss of consciousness, and oculomotor and vestibular dysfunction. The theory's reliance on sensory input emphasizes the importance of putative mechanisms whose initiating cause is known to have been present for every head trauma. This is in contrast to the century-long focus on mechanisms whose initiating cause, brain injury, is undetectable by clinical exam, neuroimaging, and bioassay in fully 60% of all head trauma, i.e., 70-75% of all mild TBI. As formulated and described, the theory is readily testable and falsifiable.
每当一个人头部受到撞击时,他们会接收到多种非典型的感觉输入,通常包括疼痛。这些直接刺激中枢神经系统。然而,感觉输入作为神经生理功能障碍和脑震荡后症状的病因从未被探讨过。本文提出了一种关于脑震荡的感觉驱动神经生理机制的新理论:(i)该机制与头部瞬间撞击存在因果联系;(ii)其时间进程和其他特性与迄今为止观察到的急性、亚急性和慢性症状的情况相符;(iii)该机制会产生具有实验可测量结果的可测试问题。该理论的主要观点是,创伤引起的包括突显网络(SN)和蓝斑(LC)在内的关键脑区兴奋,会在无症状神经功能所依赖的稳定网络兴奋性模式中产生持续的功能失调改变。这种机制在任何身体创伤中都会起作用,无论头部是否受到撞击。这是因为非典型、疼痛以及其他高强度的感觉刺激会激发SN,进而激发LC,在大脑中广泛诱导可塑性。许多这些感觉刺激可能会在恢复期持续存在,并且在大脑具有可塑性时,使一个或另一个网络学习到改变的、可能功能失调的网络兴奋性模式。该理论的次要观点是,头部受到撞击时,脑干和中脑内高强度感觉刺激的汇聚可导致通常独立发挥作用的脑干核之间的神经生理耦合,即脑干串扰(BCT)。正是BCT导致了头部创伤特有的体征和症状,例如意识丧失、动眼神经和前庭功能障碍。该理论对感觉输入的依赖强调了某些假定机制的重要性,这些机制的起始原因已知在每次头部创伤中都存在。这与长达一个世纪以来对那些起始原因(脑损伤)的关注形成对比,在所有头部创伤中,有60%(即所有轻度创伤性脑损伤的70 - 75%)通过临床检查、神经影像学和生物检测都无法检测到脑损伤。按照所阐述和描述的内容,该理论很容易进行测试和证伪。