Excitatory-Inhibitory Homeostasis and Diaschisis: Tying the Local and Global Scales in the Post-stroke Cortex

 No clue. You'll have to ask your doctor.

Excitatory-Inhibitory Homeostasis and Diaschisis: Tying the Local and Global Scales in the Post-stroke Cortex

Francisco Páscoa dos Santos^1,2,3 and Paul F. M. J. Verschure^2,4*

• ¹Eodyne Systems SL, Barcelona, Spain
• ²Laboratory of Synthetic, Perceptive, Emotive and Cognitive Systems (SPECS), Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain
• ³Department of Information and Communications Technologies (DTIC), Universitat Pompeu Fabra (UPF), Barcelona, Spain
• ⁴Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain

Maintaining a balance between excitatory and inhibitory activity is an essential feature of neural networks of the neocortex. In the face of perturbations in the levels of excitation to cortical neurons, synapses adjust to maintain excitatory-inhibitory (EI) balance. In this review, we summarize research on this EI homeostasis in the neocortex, using stroke as our case study, and in particular the loss of excitation to distant cortical regions after focal lesions. Widespread changes following a localized lesion, a phenomenon known as diaschisis, are not only related to excitability, but also observed with respect to functional connectivity. Here, we highlight the main findings regarding the evolution of excitability and functional cortical networks during the process of post-stroke recovery, and how both are related to functional recovery. We show that cortical reorganization at a global scale can be explained from the perspective of EI homeostasis. Indeed, recovery of functional networks is paralleled by increases in excitability across the cortex. These adaptive changes likely result from plasticity mechanisms such as synaptic scaling and are linked to EI homeostasis, providing a possible target for future therapeutic strategies in the process of rehabilitation. In addition, we address the difficulty of simultaneously studying these multiscale processes by presenting recent advances in large-scale modeling of the human cortex in the contexts of stroke and EI homeostasis, suggesting computational modeling as a powerful tool to tie the meso- and macro-scale processes of recovery in stroke patients.

Stroke and Diaschisis

In stroke, disruptions in blood flow in the central nervous system lead to focal lesions in the brain or spinal cord, causing it to be one of the most burdening disorders in economically advantaged countries (Campbell and Khatri, 2020). As a result of such lesions, patients experience a broad range of symptoms, with deficits in motor (e.g., hemiparesis), sensory (e.g., hemianopia) and higher-order cognitive processes (e.g., aphasia, hemispatial neglect) (Musuka et al., 2015; Campbell and Khatri, 2020), even leading to neuropsychiatric deficits such as depression (Towfighi et al., 2017) and dementia (Leys et al., 2005). While some of the effects of stroke can be directly attributed to loss of function of lesioned areas (Siegel et al., 2016), its effects extend beyond the lesioned area involving multiple areas across the cortex, a phenomenon known as diaschisis. The term diaschisis, coined by von Monakow (1914), first pertained to a remote loss in excitability following focal lesion impacting the function of brain areas distant to the lesion. Since, then the topic of diaschisis was further elaborated in the following century (Feeney and Baron, 1986), mainly focusing on changes in excitability affecting the local excitatory-inhibitory (EI) balance of distant cortical networks. However, the measurable effects of stroke are not limited to the mesoscale of disruptions in EI balance, extending into large-scale cortical dynamics, such as functional interactions between distant regions. Therefore, extensions to the concept of diaschisis have been proposed in recent years, suggesting remote disruptions in functional connectivity as a relevant aspect of the process (Campo et al., 2012; Carrera and Tononi, 2014). With this recent expansion, attempting to bridge these two types of diaschisis emerging on different spatial scales is, therefore, a relevant issue, not only to better understand possible common physiological causes, but also to inform therapeutical strategies, thus improving post-stroke recovery. That said, in this review, we summarize the main findings related to diaschisis, both regarding functional connectivity (FC) and excitability, and link long-term changes in excitability to cortical plasticity mechanisms related to EI homeostasis, suggesting that the effects of these local processes extend beyond the scale of local EI balance regulation, into large-scale network dynamics. In addition, we summarize the recent advances in computational modeling of stroke, proposing modeling as a framework for the study of the concurrent evolution of FC and excitability in the post-stroke brain.

More at link.