Recovery of Theta Frequency Oscillations in Rats Following Lateral Fluid Percussion Corresponds With a Mild Cognitive Phenotype

Abstract

Whether from a fall, sports concussion, or even combat injury, there is a critical need to identify when an individual is able to return to play or work following traumatic brain injury (TBI). Electroencephalogram (EEG) and local field potentials (LFP) represent potential tools to monitor circuit-level abnormalities related to learning and memory: specifically, theta oscillations can be readily observed and play a critical role in cognition. Following moderate traumatic brain injury in the rat, lasting changes in theta oscillations coincide with deficits in spatial learning. We hypothesized, therefore, that theta oscillations can be used as an objective biomarker of recovery, with a return of oscillatory activity corresponding with improved spatial learning. In the current study, LFP were recorded from dorsal hippocampus and anterior cingulate in awake, behaving adult Sprague Dawley rats in both a novel environment on post-injury days 3 and 7, and Barnes maze spatial navigation on post-injury days 8–11. Theta oscillations, as measured by power, theta-delta ratio, peak theta frequency, and phase coherence, were significantly altered on day 3, but had largely recovered by day 7 post-injury. Injured rats had a mild behavioral phenotype and were not different from shams on the Barnes maze, as measured by escape latency. Injured rats did use suboptimal search strategies. Combined with our previous findings that demonstrated a correlation between persistent alterations in theta oscillations and spatial learning deficits, these new data suggest that neural oscillations, and particularly theta oscillations, have potential as a biomarker to monitor recovery of brain function following TBI. Specifically, we now demonstrate that oscillations are depressed following injury, but as oscillations recover, so does behavior.

Understanding Primary Blast Injury: High Frequency Pressure Acutely Disrupts Neuronal Network Dynamics in Cerebral Organoids

“… 40 , 41 These subthreshold membrane oscillations were shown to be modulated by parvalbumin interneuron inhibition. 42 Further, theta oscillations in this bandwidth have been implicated in mild TBI studies both in rodent models 43 and patients. 44 High frequency pressure waves (5000 Hz) may decouple network synchronization by disrupting synaptic transmissions between inhibitory interneurons and excitatory cortical neurons.…”

Peering into the Brain through the Retrosplenial Cortex to Assess Cognitive Function of the Injured Brain

“… 95 Another study reported a significant reduction in place cells number and the spatial features of the remaining place cells after fluid percussion injury, 99 whereas recovery of theta frequency oscillations occurred commensurate with improved behavior. 101 Other studies that investigated neural activity in vitro or ex vivo reported long-term potentiation alterations, 102 hyperexcitability and reduced threshold for seizure-like activity, 80 and synaptic deficits, 103 in agreement with in vivo deficits and confirming the presence of abnormal synaptic and network activity post-TBI.…”

Modified mouse model of repeated mild traumatic brain injury through a thinned‐skull window and fluid percussion

“…Since mTBI disrupts the dynamic range of neural activity indexed by neural oscillations, therefore, measuring frequency oscillation is very helpful to detect neural networks and neurological dysfunctions in resting conditions (Atlan & Margulies, 2019; Dunkley et al, 2015; Ondek et al, 2020; Zhang et al, 2020). Parallel to Ca 2+ signaling study, we explored the power changes of several frequency bands in layer 2/3 neurons at the impact site using extracellular LFPs recording on 5 DPI.…”

“…Moreover, rmTBI mice showed significantly higher theta band powers in the injured motor cortex compared with control mice, and is in line with previous findings that increased diffuse theta rhythm is observed in mTBI patients, which may return to normal within hours or many weeks (Dunkley et al, 2015; Ianof & Anghinah, 2017). However, theta frequency oscillations in the anterior cingulate cortex (ACC) (Ondek et al, 2020), medial septum, and hippocampus (Lee et al, 2013, 2015) were found disrupted in moderate TBI rats. It is interesting that Ondek et al found the alteration in theta power in ACC persist from 3 DPI to 7 DPI, while the hippocampal theta power decreased at 3 DPI, but resolved by 7 DPI (Ondek et al, 2020).…”