Peg Forest Rehabilitation - A novel spatial navigation based cognitive rehabilitation paradigm for experimental neurotrauma

Abstract

Traumatic brain injury (TBI) results from mechanical forces applied to the head. Ensuing cascades of complex pathophysiology transition the injury event into a disease process. The enduring constellation of emotional, somatic, and cognitive impairments degrade quality of life for the millions of TBI survivors suffering from long-term neurological symptoms. Rehabilitation strategies have reported mixed results, as most have not focused on specific symptomatology or explored cellular processes. The current experiments evaluated a novel cognitive rehabilitation paradigm for brain-injured and uninjured rats. The arena is a plastic floor with a cartesian grid of holes for plastic dowels to create new environments with the rearrangement of threaded pegs. Rats received either two weeks of Peg Forest rehabilitation (PFR) or open field exposure starting at 7 days post-injury; or one week starting at either day 7 or 14 post-injury; or served as caged controls. Cognitive performance was assessed on a battery of novel object tasks at 28 days post-injury. The results revealed that two weeks of PFR was required to prevent the onset of cognitive impairments, while one week of PFR was insufficient regardless of when rehabilitation was initiated after injury. Further assessment of the task showed that novel daily arrangements of the environment were required to impart the cognitive performance benefits, as exposure to a static arrangement of pegs for PFR each day did not improve cognitive performance. The results indicate that PFR prevents the onset of cognitive disorders following acquired a mild to moderate brain injury, and potentially other neurological conditions.

Keywords: Cognitive impairment; Cognitive rehabilitation; Exploratory behavior; Improved cognition; Spatial navigation; Traumatic brain injury.

Fig. 1.

A) Examples of the Peg Forest arenas used in Experiment 1 (left) and Experiment 2 and 3 (right). B) Behavioral schematics for the cognitive assessments used in the study. The top schematic is the novel object recognition task to the novel location task. For novel object recognition (NOR), rats are presented with two identical objects (O1 * and O2 *). Following a 4 h break, (O2 *) replaced by a novel object (O3 •) to test recognition memory. The test for NOR serves as the sample for novel object location (NOL) and 24 h after NOR testing O3 • was placed in the same location as the previous day and O1 was moved to the adjacent corner in the arena. For temporal order recognition (TOR), rats explore 2 copies of an object for two introductory trials lasting 5 min, and are given a 3 min delay, then a second pair of objects are presented for 5 min. After a 5 min delay, the test trial (5 min) consists of one of each object. Target objects for the three tasks are outlined by a box.

Fig. 2.

Behavioral performance from experiment 1. A) Distance travelled by the rats in PFR (solid lines) and OFR (dashed lines). Injured rats (open circles) traveled more than sham (solid circles), though not significant. OFR rats traveled significantly further than PFR rats as they did not have pegs to investigate. B) Short-term memory was assessed using a NOR task over the course of two days (Fig. 1B). For the NOR task, brain-injured OFR and CC rats performed significantly worse than their sham counterparts. Brain-injured PFR rats performed significantly better than the brain-injured CC rats, and were not significantly different from the three sham groups. C) Long-term memory was assessed using a NOL task. Brain-injured OFR and CC rats performed significantly worse than their sham counterparts. Brain-injured PFR rats performed significantly better than the brain-injured OFR and CC rats, and were not significantly different from the three sham groups. D) Working-memory was assessed using a TOR task. Brain-injured OFR and CC rats performed significantly worse than their sham counterparts. Brain-injured PFR rats performed significantly better than the brain-injured OFR and CC rats and were not significantly different from the three sham groups. Dotted line represents chance performance. Data are presented as mean ± SEM with statistical significance assigned at p < 0.05. * over a line indicates a significant comparison, * in the bar indicates a significant comparison to the respective sham group. OFR, open field rehabilitation; PFR, Peg Forest Rehabilitation; S, sham; I, injured; CC, caged control; NOR, novel object recognition; NOL, novel object location; TOR, temporal order recognition.

Fig. 3.

Behavioral performance from experiment 2. All rats were brain-injured. A) Distance travelled by the rats when exposed to one week of PFR starting 7 DPI (solid line) and 14 DPI (dashed line). There were no significant differences between the two groups. Note that cage-control animals were not exposed to the peg forest. B) Short-term memory was assessed using NOR in PFR and CC rats. There were no significant differences between rats in any condition. C) Long-term memory was assessed using NOL. There were no significant differences for rats in any condition. D) Working-memory was assessed using TOR. There were no significant differences for rats in any condition. Dotted line represents chance performance. Data are presented as mean ± SEM with statistical significance assigned at p < 0.05. CC, caged control; NOR, novel object recognition; NOL, novel object location; TOR, temporal order recognition; DPI, days post-injury.

Fig. 4.

Behavioral performance from experiment 3. All rats were brain-injured. There were no significant differences between sexes, and rats were combined for each group. See supplementary material for disaggregated data. A) Distance travelled by rats when exposed to the static (invariable; solid line) and dynamic (novel; dashed line) PFR. There were no significant differences in distance traveled between the two conditions. B) Short-term memory was assessed using NOR. Rats in the dynamic condition performed significantly better than rats in the static condition. C) Long-term memory was assessed using NOL. Rats in the dynamic condition performed significantly better than rats in the static condition. D) Working memory was assessed using TOR. Rats in the dynamic condition performed significantly better than rats in the static condition. Dotted line represents chance performance. Data are presented as mean ± SEM with statistical significance assigned at p < 0.05. * over a line indicates a significant comparison, * in the bar indicates a significant comparison to the respective sham group. * indicates a significant comparison. NOR, novel object recognition; NOL, novel object location; TOR, temporal order recognition.