Stroke and the Connectome: How Connectivity Guides Therapeutic Intervention

Abstract

Connections between neurons are affected within 3 min of stroke onset by massive ischemic depolarization and then delayed cell death. Some connections can recover with prompt reperfusion; others associated with the dying infarct do not. Disruption in functional connectivity is due to direct tissue loss and indirect disconnections of remote areas known as diaschisis. Stroke is devastating, yet given the brain's redundant design, collateral surviving networks and their connections are well-positioned to compensate. Our perspective is that new treatments for stroke may involve a rational functional and structural connections-based approach. Surviving, affected, and at-risk networks can be identified and targeted with scenario-specific treatments. Strategies for recovery may include functional inhibition of the intact hemisphere, rerouting of connections, or setpoint-mediated network plasticity. These approaches may be guided by brain imaging and enabled by patient- and injury-specific brain stimulation, rehabilitation, and potential molecule-based strategies to enable new connections.

Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

“…At the local peri-infarct areas, ChR2 photostimulation of the peri-infarct zone revealed a heterogeneous recovery; some areas (anterior-lateral) remained depressed while others areas (posterior-medial) recovered by 8 weeks after stroke, indicating a nonuniform recovery of peri-infarct areas [82]. These findings are consistent with the notion that stroke affects a brain-wide network and further supports the involvement of noninjured remotely connected regions in stroke recovery [22,24]. Owing to the limitation of the VSD technique, this study did not investigate involvement of prefrontal circuits or subcortical circuits.…”

“…As stroke can disrupt functional connections and cause brain-wide network changes [22], it is important to understand the spatial and temporal progression of neural circuit dynamics and to identify which neural circuits are beneficial for stroke recovery. Brain imaging studies in stroke patients have yielded important insights about functional cortical remapping [23][24][25].…”

“…Brain injury such as stroke can disrupt this balance and cause changes in both the lesion area and remotely connected regions [22]. Wide-scale circuit-level remapping can occur early after stroke without formation of new structural connections; this can be partly due to the disinhibition that occurs after stroke [23,139].…”

“…In addition, stroke produces a loss of proper sensory motor maps, and sensory representations can remap onto nearby areas. At 1-2 months after stroke, surviving neurons that were originally highly limb selective can evolve into responding to multiple limbs [22,144]. This adaptive plasticity within neuronal networks contributes to cortical remapping and recovery after stroke [8,22,144].…”

Cerebral plasticity and connectopathies: mechanisms of comorbidity of neurological diseases and depression

“…Некоторые связи восстанавливаются после реперфузии, а другие, ассоциированные с гибнущи-ми нейронами, не восстанавливаются. Нарушение функ-циональных связей может быть связано с потерей нейро-нов или непрямыми эффектами в отдаленных областях мозга -диашизом [10]. Не удивительно, что структурный и межрегиональный коннектомный нейроимиджинг про-демонстрировал высокий клинический потенциал и при травматическом повреждении мозга [11,12].…”