The neural correlates of cognitive dysfunction in phantom sounds

Highlights

• The correlation between tinnitus and cognitive impairment.

• Proposing neurophysiological changes to explain it in humans.

• The hippocampal area are related to cognitive dysfunction in tinnitus.

Abstract

Tinnitus is an auditory phantom percept with a tone, hissing or buzzing sound in the absence of an objective physical sound source. It has been shown that tinnitus can lead to emotional and cognitive impairment and people with tinnitus perform worse than a control group on different cognitive tasks. The hippocampus is known to play an important role in cognitive performance, and also in the pathophysiology of tinnitus. Hippocampal deficits have been described in animal models of tinnitus and in tinnitus patients a decrease in grey matter in the hippocampus has been demonstrated. Nineteen patients with tinnitus and fifteen healthy controls performed different cognitive processing tasks and underwent an EEG with source analysis to investigate the relationship between tinnitus loudness, tinnitus distress and tinnitus duration, cognitive impairment and neurophysiological changes in the hippocampus. Results show that both tinnitus loudness, tinnitus distress and tinnitus duration correlated positively with different cognitive measures (trail making test, Montreal cognitive assessment, mini mental state examination). It was also shown that these cognitive measures correlate with beta activity in the hippocampus, the pregenual and subgenual anterior cingulate cortex extending into the right insula. A region of interest analysis further confirms that beta activity in the left and right hippocampal area correlated with the trail making performance. In conclusion, these results support for the first time the notion that cognitive changes in tinnitus patients are associated with changes in hippocampal activity as well as the anterior cingulate and insula.

Introduction

Tinnitus is an auditory phantom percept with a tone, hissing, or buzzing sound in the absence of any objective physical sound source (Jastreboff, 1990). The American Tinnitus Association estimates that 50 million Americans perceive tinnitus, and that 12 million of these people have chronic tinnitus that prompts them to seek medical attention. Since tinnitus prevalence increases with age (Hoffman and Reed, 2004), these numbers are expected to increase due to the demographic development. The constant awareness of this phantom sound often causes a considerable amount of distress. Between 6 and 25% of the affected people report symptoms that are severely debilitating (Baguley, 2002, Eggermont and Roberts, 2004) and 2 to 4% of the whole population suffers from the worst severity degree. In this group the condition leads to a noticeable decrease in the quality of life (Axelsson and Ringdahl, 1989). Psychological complications such as lifestyle detriment, emotional difficulties, sleep deprivation, work hindrance, interference with social interaction and decreased overall health have been attributed to tinnitus (Folmer et al., 1999, Folmer and Griest, 2000, Scott and Lindberg, 2000, Tyler and Baker, 1983).

But apart from social and emotional problems, studies have also documented cognitive impairments in persons with tinnitus (Hallam et al., 2004, Jacobson et al., 1996, McKenna et al., 1996, Wilson et al., 1991). Tinnitus patients performed more poorly than a control group on arithmetic, letter cancelation, verbal fluency, and trail making tasks (McKenna et al., 1996). As such, tinnitus might be associated with a reduced cognitive functioning on working and long-term memory as well as on aspects of selective and divided attention (Andersson et al., 2000, Andersson et al., 2002, Hallam et al., 2004, Rossiter et al., 2006).

Rats exposed to blast waves showed cognitive deficits in behavioral testing (Cernak et al., 2001, Saljo et al., 2009, Saljo et al., 2010, Saljo et al., 2011). Recent data from combat personnel exposed to excessive noise levels, explosions and blast waves show not only severe hearing loss and tinnitus but also severe cognitive and memory impairment (Cave et al., 2007). Although cognitive complaints are common among tinnitus patients, only a few studies have adopted an objective approach to examine the nature of these cognitive deficits. That is, the cognitive performance deficits may be associated with neurophysiological changes in people with tinnitus.

The hippocampus is known to play an important role in learning, memory, mood, spatial navigation and also in cognitive performance (Becker and Wojtowicz, 2007, Lafenetre et al., 2011, Moscovitch et al., 2005). The involvement of the hippocampal area in tinnitus has been documented by transient tinnitus diminution after suppression of the amydalo-hippocampal complex by supraselective amobarbital injections in the anterior choroidal artery (De Ridder et al., 2006). Further support for involvement of the hippocampus in the pathophysiology of tinnitus comes from an imaging study which has demonstrated in tinnitus patients a decrease in grey matter in the hippocampus (Landgrebe et al., 2009). It has been suggested that the involvement of the hippocampal area might reflect a paradoxical memory (Shulman, 1995), or an aversive auditory memory trace (De Ridder et al., 2011). In animal models of noise trauma and auditory overstimulation, both of which are known to generate tinnitus, hippocampal changes have been described, interfering with hippocampal neurogenesis (Kraus et al., 2010) and impairing place cell function (Goble et al., 2009). Thus the question remains whether cognitive deficits described in humans in tinnitus might be related to hippocampal involvement.

The present study focused on objective measures of cognition (i.e. TMT-A, TMT-B MoCA and MMSE) which are associated with hippocampal activity (Leirer et al., 2010), and especially medial temporal lobe atrophy (Oosterman et al., 2010). These measures have been used across a variety of studies and clinical populations, and are a cognitive processing. The primary goal of this study is to determine whether tinnitus influences cognitive function in humans, in view of hippocampal place cell function changes described in animals (Goble et al., 2009), and whether these changes are associated with activity changes in the hippocampus. Hence, we use source localized EEG recordings of tinnitus patients and analyzed the spectral components related to the trail making cognitive measure, as well as the Montreal cognitive assessment and the mini mental state examination.