Metabolic imaging of rat brain during pharmacologically-induced tinnitus

Abstract

Although much is known about the perceptual characteristics of tinnitus, its neural origins remain poorly understood. We investigated the pattern of neural activation in central auditory structures using positron emission tomography (PET) imaging in a rat model of salicylate-induced tinnitus. Awake rats were injected with the metabolic tracer, fluorine-18 fluorodeoxyglucose (FDG), once in a quiet state (baseline) and once during salicylate-induced tinnitus. Tinnitus was verified using a behavioral technique. Brain imaging was performed using a high-resolution microPET scanner. Rats underwent magnetic resonance imaging (MRI) and reconstructed MRI and microPET images were fused to identify brain structures. FDG activity in brain regions of interest were quantified and compared. MicroPET imaging showed that FDG activity in the frontal pole was stable between baseline and tinnitus conditions, suggesting it was metabolically inert during tinnitus. Inferior colliculi (p=0.03) and temporal cortices (p=0.003) showed significantly increased FDG activity during tinnitus relative to baseline; activity in the colliculi and temporal cortices increased by 17% ± 21% and 29% ± 20%, respectively. FDG activity in the thalami also increased during tinnitus, but the increase did not reach statistical significance (p=0.07). Our results show increased metabolic activity consistent with neuronal activation in inferior colliculi and auditory cortices of rats during salicylate-induced tinnitus. These results are the first to show that microPET imaging can be used to identify central auditory structures involved in tinnitus and suggest that microPET imaging might be used to evaluate the therapeutic potential of drugs to treat tinnitus.

Neural activity underlying tinnitus generation: Results from PET and fMRI

“…Additional neural plasticity was observed following acoustic (pure-tone) trauma, which resulted in a change in the cortical tonotopic map (Komiya and Eggermont, 2000;Eggermont, 2006). Recently, salicylate-induced tinnitus in rats was found to increase FDG activity in the auditory cortex using a micro PET imaging technique (Paul et al, 2009). Together, these data show that induced hearing loss causes changes in both the level of activity and the synchrony between neurons of the PAC.…”

Salicylate toxicity model of tinnitus

“…Paul and colleagues (2009) used a metabolic tracer, fluorine-18 deoxyglucose (FDG), and positron imaging tomography (PET) to image activity in the entire rat brain following a single dose of sodium salicylate (250 mg/kg i.p.). Metabolic activity was significantly increased in IC and AC; a small trend toward an increase was measured in the thalamus, but this did not reach statistical significance.…”

Differential effects of sodium salicylate on current-evoked firing of pyramidal neurons and fast-spiking interneurons in slices of rat auditory cortex

“…Systemic administration of SS increases the amplitude of sound-evoked local field potentials recorded from the auditory cortex (Yang et al, 2007) and increases the gain of the central auditory system (Sun et al, 2009). Furthermore, positron emission tomography reveals a metabolic increase in the central auditory structures of animals following SS-treatment (Paul et al, 2009). These lines of evidence suggest a need to further study how SS changes functional behaviors of central auditory neurons.…”