Biomedical subjects

T D Griffiths

Publications and source records attributed to T D Griffiths.

At least 19 recordsLinked to original sources

PubMed2001

Psychophysical evaluation of cochlear hair cell damage due to the A3243G mitochondrial DNA mutation.

Mitochondrial dysfunction is an important cause of human deafness, implicated in genetic deafness, toxin and noise damage. We assessed the mechanism of cochlear dysfunction in a population of 11 subjects with a specific mitochondrial disorder caused by the A3243G mitochondrial DNA mutation. Psychophysical tests were carried out to assess the inner and outer hair cell functions in vivo. Inner hair cell function was assessed using a measure of hearing threshold in the presence of "threshold-equalizing noise" which can indicate "dead regions" where the transduction mechanism fails. Outer hair cell function was assessed by using the notched-noise method to measure auditory filter width, dependent on active mechanisms in the outer hair cell. The results support the conclusion that this mitochondrial disorder causes both inner and outer hair cell dysfunctions. Evidence of inner hair cell dysfunction was found mainly in basal (high frequency) regions of the cochlea and occurred even in some subjects with only mild hearing loss. Evidence of outer hair cell dysfunction was found in some instances where pure tone threshold was at or close to normal. The common occurrence of dead regions in the basal cochlea has treatment implication for this form of deafness; such people may not be helped by amplification of high frequencies.

Adult↗

PubMed2001

The Newcastle Auditory Battery (NAB). A temporal and spatial test battery for use on adult naïve subjects.

A battery of tests for assessing the perception of temporal and spatial acoustic cues is described, together with a software platform for implementing the battery. The software runs on a personal computer either with a sound card or with widely used laboratory hardware. The battery is intended for use with neurologically impaired and other naive subjects, to allow inference at the single-subject level for any given subtest. The aim is to allow a systematic psychoacoustic evaluation of complex sound processing in single patients. Normal values are given for the threshold data for 30 naïve control subjects aged from 20 to 60 years. Future modifications of the battery are allowed by modular software architecture.

Adult↗

PubMed2001

Encoding of the temporal regularity of sound in the human brainstem.

We measured the neural activity associated with the temporal structure of sound in the human auditory pathway from cochlear nucleus to cortex. The temporal structure includes regularities at the millisecond level and pitch sequences at the hundreds-of-milliseconds level. Functional magnetic resonance imaging (fMRI) of the whole brain with cardiac triggering allowed simultaneous observation of activity in the brainstem, thalamus and cerebrum. This work shows that the process of recoding temporal patterns into a more stable form begins as early as the cochlear nucleus and continues up to auditory cortex.

Acoustic Stimulation↗

PubMed2001

The neural processing of complex sounds.

This paper considers the temporal processing of complex sounds relevant to musical analysis. Functional imaging studies, using positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG), and the psychophysical assessment of patients with lesions allow two different approaches to this. Functional imaging allows the determination of structures normally involved in temporal analysis, while patient studies allow inference about the necessary structures for temporal analysis. Both approaches suggest a hierarchal organization in the brain corresponding to the processing of music. The features of individual notes are analyzed in the pathway up to and including the auditory cortices, while higher-order patterns formed by those features are analyzed by distributed networks in the temporal lobe and frontal lobes distinct from the auditory cortices.

Auditory Perception↗

PubMed2001

Second-order modulation detection thresholds for pure-tone and narrow-band noise carriers.

Modulation perception has typically been characterized by measuring detection thresholds for sinusoidally amplitude-modulated (SAM) signals. This study uses multicomponent modulations. "Second-order" temporal modulation transfer functions (TMTFs) measure detection thresholds for a sinusoidal modulation of the modulation waveform of a SAM signal [Lorenzi et al., J. Acoust. Soc. Am. 110, 1030-2038 (2001)]. The SAM signal therefore acts as a "carrier" stimulus of frequency fm, and sinusoidal modulation of the SAM signal's modulation depth (at rate f'm) generates two additional components in the modulation spectrum at fm - f'm and fm + f'm. There is no spectral energy at the envelope beat frequency f'm in the modulation spectrum of the "physical" stimulus. In the present study, second-order TMTFs were measured for three listeners when fm was 16, 64, and 256 Hz. The carrier was either a 5-kHz pure tone or a narrow-band noise with center frequency and bandwidth of 5 kHz and 2 Hz, respectively. The narrow-band noise carrier was used to prevent listeners from detecting spectral energy at the beat frequency f'm in the "internal" stimuli's modulation spectrum. The results show that, for the 5-kHz pure-tone carrier, second-order TMTFs are nearly low pass in shape; the overall sensitivity and cutoff frequency measured on these second-order TMTFs increase when fm increases from 16 to 256 Hz. For the 2-Hz-wide narrow-band noise carrier, second-order TMTFs are nearly flat in shape for fm = 16 and 64 Hz, and they show a high-pass segment for fm = 256 Hz. These results suggest that detection of spectral energy at the envelope beat frequency contributes in part to the detection of second-order modulation. This is consistent with the idea that nonlinear mechanisms in the auditory pathway produce an audible distortion component at the envelope beat frequency in the internal modulation spectrum of the sounds.

Adult↗

PubMed2000

Frontal processing and auditory perception.

Disordered processing of the pattern in sound over time has been observed in a number of clinical disorders, including developmental dyslexia. This study addresses the brain mechanisms required for the perception of such a pattern. We report the systematic evaluation of temporal perception in a patient with a single intact right auditory cortex and a large right frontal lobe lesion. A striking dissociated deficit was demonstrated in the perception of temporal pattern at the level of tens or hundreds of milliseconds. This proves that, contrary to common belief, mechanisms in the pathway up to and including the primary auditory cortex are not sufficient for the normal perception of temporal pattern. This work suggests a need for frontal processing for the normal perception of auditory pattern.

Adult↗

PubMed2000

Human brain areas involved in the analysis of auditory movement.

This work tests the hypothesis that a network of areas involving bilateral premotor cortex and right parietal cortex subserves the analysis of sound movement. The components of this network have been examined at the level of individual subjects in a study where 720 fMRI scans were acquired per subject. Additionally, the effect of movement direction was investigated by varying this property systematically. Linear sound ramps that are perceived as movement toward one side of the head or the other were used in an experiment in which the principal contrast was between movement, and a stationary control stimulus made up of identical component interaural phase and amplitude cues. In a group analysis, the network of bifrontal and right parietal areas suggested by previous work was confirmed. The frontal activation included both dorsal premotor activity in the region of the frontal eye fields and discrete ventral premotor activation in an area corresponding to primate areas for multimodal spatial analysis and motor planning. The right parietal activation included both superior and inferior parietal cortex. Analysis of the individual data showed a similar pattern of activation in each subject, with the greatest variability within the right parietal area. The pattern of activation did not vary when the direction of movement was varied, suggesting that both directions of movement are represented in the network we have demonstrated.

Acoustic Stimulation↗

PubMed2000

The spectrum of hearing loss due to mitochondrial DNA defects.

Heteroplasmic mitochondrial DNA (mtDNA) defects are an important cause of neurological disease. Although hearing impairment is common in patients with mtDNA defects, the spectrum and pathophysiology of the hearing loss is not well characterized. We therefore studied the relationship between cochlear and brainstem auditory function in 23 patients harbouring a range of different mtDNA mutations. Based upon the pure tone audiogram, patients fell into three distinct groups: (i) normal hearing, (ii) mild to moderate predominantly high frequency hearing loss, and (iii) severe or profound hearing loss at all frequencies. Within this study group only certain genetic defects were associated with hearing loss, and for individuals harbouring the A3243G point mutation, the severity of the hearing loss correlated with the percentage level of mutated mtDNA (mutation load) in skeletal muscle. The 10 patients who had a moderate hearing loss or less had normal brainstem auditory evoked responses and MRI, but it was not possible to interpret the brainstem auditory evoked responses in 13 patients with severe hearing loss. Otoacoustic emissions were absent in patients with a moderate or more severe hearing loss. These findings are consistent with a predominantly cochlear origin for the hearing deficit, which is determined by the precise genetic defect and the percentage mutation load.

Adult↗

PubMed2000

Musical hallucinosis in acquired deafness. Phenomenology and brain substrate.

Six subjects with musical hallucinations following acquired deafness are described. The subjects all experienced the condition in the absence of any other features to suggest epilepsy or psychosis. I propose a neuropsychological model for the condition consistent with detailed observation of the subjects' phenomenology. The model is based on spontaneous activity within a cognitive module for the analysis of temporal pattern in segmented sound. Functional imaging was carried out to test the hypothesis that musical hallucinosis is due to activity within such a module, for which the neural substrate is a distributed network distinct from the primary auditory cortex. PET was carried out on the six subjects to identify areas where brain activity increased as a function of the severity of the hallucination. In a group analysis, no effect was demonstrated in the primary auditory cortices. Clusters of correlated activity were demonstrated in the posterior temporal lobes, the right basal ganglia, the cerebellum and the inferior frontal cortices. This network is similar to that previously demonstrated during the normal perception and imagery of patterned-segmented sound, and is consistent with the proposed neuropsychological and neural mechanism.

Aged↗

PubMed1999

A common neural substrate for the analysis of pitch and duration pattern in segmented sound?

The analysis of patterns of pitch and duration over time in natural segmented sounds is fundamentally relevant to the analysis of speech, environmental sounds and music. The neural basis for differences between the processing of pitch and duration sequences is not established. We carried out a PET activation study on nine right-handed musically naive subjects, in order to examine the basis for early pitch- and duration-sequence analysis. The input stimuli and output task were closely controlled. We demonstrated a strikingly similar bilateral neural network for both types of analysis. The network is right lateralised and includes the cerebellum, posterior superior temporal cortices, and inferior frontal cortices. These data are consistent with a common initial mechanism for the analysis of pitch and duration patterns within sequences.

Adult↗

PubMed1999

Cortical activation during perception of a rotating wide-field acoustic stimulus.

We describe sound stimuli that produce the perception of complete rotation around the head. Such stimuli are analogous to wide-field motion stimuli used in visual research, though auditory stimuli, unlike visual stimuli, can be perceived at any point around the head; they are the only cues for spatial perception behind the subject. Using PET on six subjects, we have compared regional brain activity during the perception of such motion stimuli, with the perception of a control stimulus producing equivalent amplitude changes without rotation. Rotation produced activation of the premotor cortex bilaterally and the right superior parietal cortex. The premotor activation involved the frontal eye fields and ventral premotor areas. The bifrontal and right parietal activation is consistent with previous demonstrations of activation within a frontoparietal network of areas during perception of a linear motion stimulus. The inferior premotor activation in this experiment may reflect preparation for head turning in response to auditory targets that cannot be tracked visually.

Acoustic Stimulation↗

PubMed1999

Human complex sound analysis.

The analysis of complex sound features is important for the perception of environmental sounds, speech and music, and may be abnormal in disorders such as specific language impairment in children, and in common adult lesions including stroke and multiple sclerosis. This work addresses the problem of how the human auditory system detects features in complex sound, and uses those features to perceive the auditory world. The work has been carried out using two independent means of testing the same hypotheses; detailed psychophysical studies of neurological patients with central lesions, and functional imaging using positron emission tomography and functional magnetic resonance imaging of normal subjects. The psychophysical and imaging studies have both examined which brain areas are concerned with the analysis of auditory space, and which are concerned with the analysis of timing information in the auditory system. This differs from many previous human auditory studies, which have concentrated on the analysis of sound frequency. The combined lesion and functional imaging approach has demonstrated analysis of the spatial property of sound movement within the right parietal lobe. The timing work has confirmed that the primary auditory cortex is active as a function of the time structure of sound, and therefore not only concerned with frequency representation of sounds.

Auditory Perception↗

PubMed1998

A distinct low-level mechanism for interaural timing analysis in human hearing.

The detection of phase or timing differences, and amplitude differences between the two ears are cues for the spatial analysis of sound by humans. Previous physiological and anatomical studies of animals suggest that phase and amplitude differences between the ears may depend on different pathways, though human psychophysical studies suggest that interaural phase and amplitude differences between the two ears may be coded in the same way. Here we describe detailed psychophysical analysis of a subject with multiple sclerosis affecting the brain stem. He has a complete deficit in the detection of phase between the ears with preserved detection of interaural amplitude. The results prove that a distinct mechanism exists in humans for interaural phase detection.

Acoustic Stimulation↗

PubMed1998

Sensitivity to dynamic auditory and visual stimuli predicts nonword reading ability in both dyslexic and normal readers.

BACKGROUND: Developmental dyslexia is a specific disorder of reading and spelling that affects 3-9% of school-age children and adults. Contrary to the view that it results solely from deficits in processes specific to linguistic analysis, current research has shown that deficits in more basic auditory or visual skills may contribute to the reading difficulties of dyslexic individuals. These might also have a crucial role in the development of normal reading skills. Evidence for visual deficits in dyslexia is usually found only with dynamic and not static stimuli, implicating the magnocellular pathway or dorsal visual stream as the cellular locus responsible. Studies of such a dissociation between the processing of dynamic and static auditory stimuli have not been reported previously. RESULTS: We show that dyslexic individuals are less sensitive both to particular rates of auditory frequency modulation (2 Hz and 40 Hz but not 240 Hz) and to dynamic visual-motion stimuli. There were high correlations, for both dyslexic and normal readers, between their sensitivity to the dynamic auditory and visual stimuli. Nonword reading, a measure of phonological awareness believed crucial to reading development, was also found to be related to these sensory measures. CONCLUSIONS: These results further implicate neuronal mechanisms that are specialised for detecting stimulus timing and change as being dysfunctional in many dyslexic individuals. The dissociation observed in the performance of dyslexic individuals on different auditory tasks suggests a sub-modality division similar to that already described in the visual system. These dynamic tests may provide a non-linguistic means of identifying children at risk of reading failure.

Acoustic Stimulation↗

PubMed1998

Analysis of temporal structure in sound by the human brain.

For over a century, models of pitch perception have been based on the frequency composition of the sound. Pitch phenomena can also be explained, however, in terms of the time structure, or temporal regularity, of sounds. To locate the mechanism for the detection of temporal regularity in humans, we used functional imaging and a 'delay-and-add' noise, which activates all frequency regions uniformly, like noise, but which nevertheless produces strong pitch perceptions and tuneful melodies. This stimulus has temporal regularity that can be systematically altered. We found that the activity of primary auditory cortex increased with the regularity of the sound. Moreover, a melody composed of delay-and-add 'notes' produced a distinct pattern of activation in two areas of the temporal lobe distinct from primary auditory cortex. These results suggest a hierarchical analysis of time structure in the human brain.

Auditory Cortex↗

PubMed1998

Right parietal cortex is involved in the perception of sound movement in humans.

Changes in the delay (phase) and amplitude of sound at the ears are cues for the analysis of sound movement. The detection of these cues depends on the convergence of the inputs to each ear, a process that first occurs in the brainstem. The conscious perception of these cues is likely to involve higher centers. Using novel stimuli that produce different perceptions of movement in the presence of identical phase and amplitude modulation components, we have demonstrated human brain areas that are active specifically during the perception of sound movement. Both functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) demonstrated the involvement of the right parietal cortex in sound movement perception with these stimuli.

Acoustic Stimulation↗

PubMed1998

Neurological abnormalities in familial and sporadic schizophrenia.

Neurological assessment was carried out on patients with schizophrenia from multiply and singly affected families, their relatives, and a normal control group (214 subjects). A systematic examination was used in which abnormal signs were divided into 'primary' and 'integrative' signs. Primary signs were elicited by a standard clinical neurological examination and included signs of focal damage to nuclei and tracts, whilst integrative signs were selected as reflecting distributed brain function. The assessments were carried out to test the hypotheses that (i) neurological abnormalities are present in schizophrenia, (ii) the pattern of abnormality is different in familial and sporadic schizophrenic subjects, and (iii) the well relatives of familial (but not sporadic) schizophrenic subjects will show neurological abnormalities. An excess of primary signs compared with the controls was demonstrated in the sporadic schizophrenic group only. Both the familial schizophrenics and their first-degree relatives (but not their sporadic counterparts) showed an increase in integrative signs. The results support the existence of different mechanisms of underlying brain dysfunction in familial and sporadic schizophrenia.

Adult↗

PubMed1998

Minor physical anomalies in familial and sporadic schizophrenia: the Maudsley family study.

OBJECTIVES: (1) To test the hypothesis that minor physical anomalies are increased in patients with schizophrenia and (2) to investigate differences in the prevalence of minor physical anomalies in patients with familial and sporadic schizophrenia and their first degree relatives. METHODS: A weighted Waldrop assessment was carried out on 214 subjects in five groups: schizophrenic patients from multiply affected families; first degree relatives of these familial schizophrenic patients; sporadic schizophrenic patients; first degree relatives of these sporadic schizophrenic patients, and normal controls. Broad and narrow criteria for abnormality were defined based on the distribution of minor physical anomalies in the control group. RESULTS: (1) The total schizophrenic group did not have a significant increase in minor physical anomalies using a narrow criterion of abnormality, but did when a broader criterion was used. (2) A significant increase in the proportion of subjects with an abnormally high number of minor physical abnormalities was shown in the group of sporadic schizophrenic patients (uncorrected p<0.01). Separate analyses for males and females showed a significant increase in the male sporadic group (uncorrected p<0.05), and a smaller non-significant increase in the female sporadic group. Neither the familial schizophrenic group nor either group of first degree relatives showed any significant increases in the proportion of patients with high abnormality scores. CONCLUSION: This work supports prenatal developmental abnormality as a mechanism for sporadic, but not familial, schizophrenia.

Adult↗