Mary Lou Coad

The functional neuroanatomy of tinnitus Evidence for limbic system links and neural plasticity

We used PET to map brain regions responding to changes in tinnitus loudness in four patients who could alter tinnitus loudness by performing voluntary oral facial movements (OFMs). Cerebral blood flow was measured in four patients and six controls at rest, during the OFM, and during stimulation with pure tones. OFM-induced loudness changes affected the auditory cortex contralateral to the ear in which tinnitus was perceived, whereas unilateral cochlear stimulation caused bilateral effects, suggesting a retrocochlear origin for their tinnitus. Patients, compared with controls, showed evidence for more widespread activation by the tones and aberrant links between the limbic and auditory systems. These abnormal patterns provide evidence for cortical plasticity that may account for tinnitus and associated symptoms. Although audiologic symptoms and examinations of these patients were typical, the unusual ability to modulate tinnitus loudness with an OFM suggests some caution may be warranted in generalizing these findings.

The functional anatomy of gaze-evoked tinnitus and sustained lateral gaze

Objective: To identify neural sites associated with gaze-evoked tinnitus (GET), an unusual condition that may follow cerebellar–pontine angle surgery. Methods: The authors examined eight patients with GET and used PET to map the neural sites activated by lateral gaze in them and seven age- and sex-matched control subjects. Results: In patients with GET, tinnitus loudness and pitch increased with lateral gaze and, to a lesser extent, up and down gaze. Evidence for neural activity related to GET was seen in the auditory lateral pontine tegmentum or auditory cortex. GET-associated nystagmus appears to activate the cuneus and cerebellar vermis. These sites were found in addition to an extensive network that included frontal eye fields and other sites in frontal, parietal, and temporal cortex that were activated by lateral gaze in seven control subjects and the patients. The unilateral deafness in patients with GET was associated with expansion of auditory cortical areas responsive to tones delivered to the good ear. In addition to GET, unilateral deafness, end-gaze nystagmus, and facial nerve dysfunction were common. Conclusions: Patients with GET have plastic changes in multiple neural systems that allow neural activity associated with eye movement, including those associated with the neural integrator, to stimulate the auditory system. Anomalous auditory activation is enhanced by the failure of cross-modal inhibition to suppress auditory cortical activity. The time course for the development of GET suggests that it may be due to multiple mechanisms.

Brain imaging of the effects of lidocaine on tinnitus

Using a single-blind placebo-controlled design, we mapped lidocaine related changes in neural activity, measured by regional cerebral blood flow (rCBF) with (15)O-H(2)O positron emission tomography. Intravenous lidocaine produced both increases and decreases in the loudness of tinnitus. The change in tinnitus loudness was associated with a statistically significant change in neural activity in the right temporal lobe in auditory association cortex. Decreases in tinnitus loudness resulted in larger changes in rCBF than increases. The unilateral activation pattern associated with tinnitus, in contrast with the bilateral activation produced by a real sound, suggests that tinnitus originates in the central auditory system rather than the cochlea. In addition, generalized lidocaine effects were found in the basal ganglia, thalamus, and a region spanning the Rolandic fissure.

The effects of parental traumatic brain injury on the behaviour of parents and children.

Little is known about the effects of a parents brain injury and subsequent disabilities on the children in the family. This study examines 24 families in which one parent is brain injured. In each family the children were born before the parents injury and still lived at home at the time of interview. Reports of the uninjured parent indicate that most of the children experienced some degree of negative behavioural change after the parents injury. In 10 of the families, significant and problematic changes occurred. Types of problems included poor relationship with the injured parent, acting-out behaviour and emotional problems. Correlates of poor outcomes for the children were: (1) injured parents gender, (2) compromised parenting performance of the injured parent, (3) compromised parenting performance of the uninjured parent and (4) depression in the uninjured parent. This study points to the importance of recognizing traumatic brain injury as a major family stressor.

PET imaging of the normal human auditory system: responses to speech in quiet and in background noise

The neural mechanisms involved in listening to sentences, and then detecting and verbalizing a specific word are poorly understood, but most likely involve complex neural networks. We used positron emission tomography to identify the areas of the human brain that are activated when young, normal hearing males and females were asked to listen to a sentence and repeat the last word from the Speech in Noise (SPIN) test. Listening conditions were (1) Quiet, (2) Speech, (3) Noise, and (4) SPIN with stimuli presented monaurally to either the left ear or the right ear. The least difficult listening task, Speech, resulted in bilateral activation of superior and middle temporal gyrus and pre-central gyrus. The Noise and SPIN conditions activated many of the same regions as Speech alone plus additional sites within the cerebellum, thalamus and superior/middle frontal gyri. Comparison of the SPIN condition versus Speech revealed additional activation in the right anterior lobe of the cerebellum and right medial frontal gyrus, near the cingulate. None of the left ear-right ear stimulus comparison revealed any significant differences except for the SPIN condition that showed greater activation in the left superior temporal gyrus for stimuli presented to the right ear. No gender differences were observed. These results demonstrate that repeating the last word in a sentence activates mainly auditory and motor areas of the brain when Speech is presented, whereas more difficult tasks, such as SPIN or multi-talker Noise, activate linguistic, attentional, cognitive, working memory, and motor planning areas.

Characteristics of patients with gaze-evoked tinnitus.

Objective The authors describe symptoms and population characteristics in subjects who can modulate the loudness and/or pitch of their tinnitus by eye movements. Study Design Data were obtained by questionnaire. Setting The study was conducted at a university center and a tertiary care center. Patients Respondents had the self-reported ability to modulate their tinnitus with eye movements. Results Ninety-one subjects reported having gaze-evoked tinnitus after posterior fossa surgery involving the eighth nerve. Eighty-seven of them underwent removal of a vestibular schwannoma (acoustic neuroma), two had bilateral eighth nerve tumors (one underwent bilateral tumor removal; the other unilateral tumor removal), one underwent removal of a cholesteatoma, and one underwent removal of a glomus jugulare tumor. Seventeen subjects who had never had posterior fossa surgery reported gaze-evoked tinnitus. Of those with vestibular schwannomas, tumor size ranged from small (<2 cm) to large (>4 cm). The gender distribution was 48.3% male and 51.7% female. In 77% of patients, the gaze-evoked tinnitus was localized to the surgical ear or side of head; 21.8% had bilateral tinnitus that was louder in the surgical ear or side of head. In 86 of 87 subjects, loudness of tinnitus changed with eye movement. Eye movement away from the central (eyes centered) position increased the loudness of tinnitus in all 86 subjects who responded to this question. Seventy-three of 85 (85.9%) patients indicated that pitch changed with eye movement, with pitch increasing in 64/72 (88.9%) of them. Eighty-three of 87 (95.4%) patients reported total loss of hearing in the surgical ear. Seventy of 83 (84.3%) patients reported facial nerve problems immediately after surgery, 52 of 87 (60%) reported persistent facial weakness, and 16 of 87 (18.4%) patients reported persistent double vision. In those 17 subjects with gaze-evoked tinnitus and no posterior fossa surgery, the majority of respondents (14/17, 82.4%) were male. Conclusions Gaze-evoked tinnitus after cerebellar pontine angle surgery is more common than was previously believed. In addition, posterior fossa surgery is not a prerequisite for the development of gaze-evoked tinnitus. It is likely that gaze-evoked tinnitus is a manifestation of functional reorganization. Gaze-evoked tinnitus could result from an unmasking of brain regions that respond to multiple stimulus/response modalities, and/or from anomalous cross-modality interactions, perhaps caused by collateral sprouting.

Mapping the neural systems that mediate the Paced Auditory Serial Addition Task (PASAT).

The paced auditory serial addition task (PASAT), in which subjects hear a number-string and add the two most-recently heard numbers, is a neuropsychological test sensitive to cerebral dysfunction. We mapped the brain regions activated by the PASAT using positron emission tomography (PET) and 15O-water to measure cerebral blood flow. We parsed the PASAT by mapping sites activated by immediate repetition of numbers and by repetition of the prior number after the presentation of the next number in the series. The PASAT activated dispersed non-contiguous foci in the superior temporal gyri, bifrontal and biparietal sites, the anterior cingulate and bilateral cerebellar sites. These sites are consistent with the elements of the task that include auditory perception and processing, speech production, working memory, and attention. Sites mediating addition were not identified. The extent of the sites activated during the performance of the PASAT accounts for the sensitivity of this test and justifies its use in a variety of seemingly disparate conditions.

Covert Auditory Attention Generates Activation in the Rostral/Dorsal Anterior Cingulate Cortex

The anterior cingulate cortex (ACC) is believed to mediate conscious information processing or high-capacity attention. However, previous functional imaging studies have largely relied on tasks that involve motor function as well as attention. The work from our group utilizing an auditory continuous performance task demonstrated increased activity in a caudal division of the ACC that borders the supplementary motor area (SMA). Activity in this region was attributed to motor responding as well as attention. In the present study, we used15O H2O positron emission tomography (PET) to map brain activation during nonmotor, covert auditory attention. Our hypothesis was that a different region within the ACC, anterior to the SMA, would be active during covert attention (CA). Six men and six women were asked to monitor aurally presented syllables presented at a 1-sec interstimulus interval. During the CA condition, subjects were asked to continuously discriminate target (.19 probability) from nontarget stimuli. Simultaneous recording of event-related potentials (ERPs) confirmed the discrimination of target and nontarget stimuli and the allocation of attention capacity. Comparison of the monitored versus nonmonitored presentation of stimuli demonstrated significant activity in a rostral/dorsal division of the right ACC, anterior to SMA. Other regions of activation included the lateral prefrontal cortex and posterior superior temporal gyrus in the left hemisphere, consistent with neurocognitive models of language and vigilance. We conclude that a rostral/dorsal subdivision of the right ACC is specific for conscious attention during auditory processing, in contrast to premotor response formation.

Mapping the 40-Hz auditory steady-state response using current density reconstructions

We mapped the 40-Hz aSSR from nine normal subjects using PET-independent low-resolution electroencephalographic tomography (LORETA) as well as PET-weighted LORETA and minimum norm (MinNorm) current density reconstructions. In grand mean data, PET-independent LORETA identified seven sites with peaks in current density in right temporal lobe, right brainstem/cerebellum, right parietal lobe, left cerebellum/temporal lobe, and right frontal lobe. PET-weighted LORETA found six of the same sites as the PET-independent LORETA: the right brainstem source was eliminated and two right-frontal sources were added. Both LORETA analyses revealed considerable phase dispersion across identified sources. In both LORETA analyses, the relative time course of activation measured from an arbitrary starting phase progressed from right temporal lobe to right mid-frontal lobe to right parietal-frontal to right inferior parietal and finally to left cerebellum and left temporal lobe. MinNorm analysis incorporating PET information identified sources in the same locations as specified in the PET data. These sources were synchronized, with their amplitudes peaking almost simultaneously. Both PET-independent and PET-weighted LORETA results suggest that the aSSR is: (1) the result of a reverberating network with two or more groups of sources that recurrently excite each other or (2) the result of sequential auditory processing through various levels of a hierarchical network. In contrast, the PET-weighted MinNorm results suggest that the 40-Hz response represents simultaneous activation over widely spaced areas of the brain, perhaps due to synchronization of gamma-band activity to a common neural clock.

PET imaging of the 40 Hz auditory steady state response.

The auditory steady state response (aSSR) is an oscillatory electrical potential recorded from the scalp induced by amplitude-modulated (AM) or click/tone burst stimuli. Its clinical utility has been limited by uncertainty regarding the specific areas of the brain involved in its generation. To identify the generators of the aSSR, 15O-water PET imaging was used to locate the regions of the brain activated by a steady 1 kHz pure tone, the same tone amplitude modulated (AM) at 40 Hz and the specific regions of the brain responsive to the AM component of the stimulus relative to the continuous tone. The continuous tone produced four clusters of activation. The boundaries of these activated clusters extended to include regions in left primary auditory cortex, right non-primary auditory cortex, left thalamus, and left cingulate. The AM tone produced three clusters of activation. The boundaries of these activated clusters extended to include primary auditory cortex bilaterally, left medial geniculate and right middle frontal gyrus. Two regions were specifically responsive to the AM component of the stimulus. These activated clusters extended to include the right anterior cingulate near frontal cortex and right auditory cortex. We conclude that cortical sites, including areas outside primary auditory cortex, are involved in generating the aSSR. There was an unexpected difference between morning and afternoon session scans that may reflect a pre- versus post-prandial state. These results support the hypothesis that a distributed resonating circuit mediates the generation of the aSSR.