The Differential Effects of Acute Right- vs. Left-Sided Vestibular Deafferentation on Spatial Cognition in Unilateral Labyrinthectomized Mice

Abstract

This study aimed to investigate the disparity in locomotor and spatial memory deficits caused by left- or right-sided unilateral vestibular deafferentation (UVD) using a mouse model of unilateral labyrinthectomy (UL) and to examine the effects of galvanic vestibular stimulation (GVS) on the deficits over 14 days. Five experimental groups were established: the left-sided and right-sided UL (Lt.-UL and Rt.-UL) groups, left-sided and right-sided UL with bipolar GVS with the cathode on the lesion side (Lt.-GVS and Rt.-GVS) groups, and a control group with sham surgery. We assessed the locomotor and cognitive-behavioral functions using the open field (OF), Y maze, and Morris water maze (MWM) tests before (baseline) and 3, 7, and 14 days after surgical UL in each group. On postoperative day (POD) 3, locomotion and spatial working memory were more impaired in the Lt.-UL group compared with the Rt.-UL group (p < 0.01, Tamhane test). On POD 7, there was a substantial difference between the groups; the locomotion and spatial navigation of the Lt.-UL group recovered significantly more slowly compared with those of the Rt.-UL group. Although the differences in the short-term spatial cognition and motor coordination were resolved by POD 14, the long-term spatial navigation deficits assessed by the MWM were significantly worse in the Lt.-UL group compared with the Rt.-UL group. GVS intervention accelerated the vestibular compensation in both the Lt.-GVS and Rt.-GVS groups in terms of improvement of locomotion and spatial cognition. The current data imply that right- and left-sided UVD impair spatial cognition and locomotion differently and result in different compensatory patterns. Sequential bipolar GVS when the cathode (stimulating) was assigned to the lesion side accelerated recovery for UVD-induced spatial cognition, which may have implications for managing the patients with spatial cognitive impairment, especially that induced by unilateral peripheral vestibular damage on the dominant side.

The Effect of Galvanic Vestibular Stimulation on Visuospatial Cognition in an Incomplete Bilateral Vestibular Deafferentation Mouse Model

“…Surgical labyrinthectomy was chosen because of its relative simplicity, reliability, instantly symptom-induced, and fasterrecovered ability in comparison to vestibular neurectomy or chemical labyrinthectomy. The surgical BL procedure was done in the BVD_GVS and BVD_non-GVS groups, which were described in our published studies (14,15,30). Through a small hole made in the posterior SCC with a diamond otologic drill, the perilymph fluid was aspirated for 3 min, and then the hole was filled with collagen to prevent further leakage (14,15,30).…”

“…The surgical BL procedure was done in the BVD_GVS and BVD_non-GVS groups, which were described in our published studies (14,15,30). Through a small hole made in the posterior SCC with a diamond otologic drill, the perilymph fluid was aspirated for 3 min, and then the hole was filled with collagen to prevent further leakage (14,15,30). Using this surgical approach, we created a minor lesion (incomplete) in the vestibular apparatus while retaining the intact auditory organ.…”

“…Accordingly, the loss of vestibular inputs causes not only vertigo, dizziness, visual instability, and disturbed balance (because of impairment of the vestibulothalamo-cortical pathways, VOR, and VSR), but also deficits in spatial navigation and memory tasks, body representation, and bodily self-consciousness (through dysfunctions in the vestibular cortex and hippocampus) (13). Although unilateral vestibular deafferentation (UVD) might cause some degree of visuospatial memory deficits (14)(15)(16), bilateral vestibular deafferentation (BVD) can create prominent spatial cognitive deficiencies (17)(18)(19) that can last for up to 10 years (20). Furthermore, bilateral hippocampal atrophy was documented following BVD in the clinical investigations (20,21).…”

“…Over the past 100 years, galvanic vestibular stimulation (GVS) has been extensively applied in the pathological situations to examine the role of vestibular signals in visual stability, postural balance, locomotor control, and spatial cognition (26)(27)(28). By modulating the firing rate of vestibular afferents of both vestibular nerves and hair cells, GVS has been demonstrated to ameliorate several vestibular-related functional deficits, not only visual stability, motor coordination, and posture but also cognitive and memory impairments, particularly in UVD (14,15,29,30). Accordingly, 5 sessions of direct current, bilateral, bipolar GVS improved UVD-induced short-and long-term spatial memory deficits when the cathode (excitatory) was placed on the lesion side (14,15).…”

“…By modulating the firing rate of vestibular afferents of both vestibular nerves and hair cells, GVS has been demonstrated to ameliorate several vestibular-related functional deficits, not only visual stability, motor coordination, and posture but also cognitive and memory impairments, particularly in UVD (14,15,29,30). Accordingly, 5 sessions of direct current, bilateral, bipolar GVS improved UVD-induced short-and long-term spatial memory deficits when the cathode (excitatory) was placed on the lesion side (14,15). We designed this study to evaluate the efficacy of GVS for recovery from the spatial memory and navigation deficits caused by the vestibular deafferentation in a murine BVD model.…”