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Biomedical subjects

T D Griffiths

Publications and source records attributed to T D Griffiths.

At least 19 recordsLinked to original sources
PubMed2006

Course and outcome of acute limbic encephalitis with negative voltage-gated potassium channel antibodies.

BACKGROUND: Limbic encephalitis is a potentially treatable immunological condition. The presence of voltage-gated potassium channel antibodies (VGKC-Ab) in the cerebrospinal fluid (CSF) and serum of patients with the condition is a marker of the disease associated with a non-paraneoplastic form and good response to treatment. Recent work has highlighted absent serum VGKC-Ab and distinct immunology in patients with the paraneoplastic form of limbic encephalitis. METHODS: The cases of four patients with the typical clinical presentation, neuropsychological features and brain imaging of acute limbic encephalitis, in the absence of any evidence for associated cancer during a follow-up of at least 18 months are described here. RESULTS: All patients had negative testing for VGKC-Ab measured during their acute presentation. All patients made some recovery, although they were left with marked cognitive deficits and persistent seizures. CONCLUSION: These cases demonstrate that the absence of VGKC-Ab in limbic encephalitis does not necessarily imply a paraneoplastic form. Further work is required to establish the immunological basis for the disorder in these patients, and the optimal treatment regimen.

Acute Disease↗
PubMed2006

Proton magnetic resonance spectroscopy in frontotemporal dementia.

This study of frontotemporal dementia (FTD) was carried out to determine whether MR spectroscopy can provide an in vivo marker for the neuronal loss and gliosis that occur in this condition. We compared spectra in frontal and temporal regions known to be affected early in the course of the disease with spectra in the parietal lobe that is spared until late stages of FTD. We were interested in the relative concentrations of two compounds, NAA (a marker of neuronal integrity) and mI (a marker of gliosis), expressed as ratios to creatine (a relatively stable brain constituent). MR spectroscopy was performed on the temporal, parietal, and anterior cingulate cortices of five patients with the established semantic dementia form of FTD, two patients with the frontal form of FTD and 13 age matched controls. Structural MRI and neuropsychometry were also performed. Patients with FTD had reduced NAA/Cr in frontal and temporal, but not parietal lobes. The two patients with the frontal form of FTD had increased mI/Cr in their cingulate cortices. These data show for the first time that MR spectroscopy can reveal regionally selective abnormalities in patients with FTD. This opens up the possibility of using MR spectroscopy as a clinical tool to identify earlier presentations of the condition.

Aged↗
PubMed2006

Processing the acoustic effect of size in speech sounds.

The length of a vocal tract is reflected in the sound it is producing. The length of the vocal tract is correlated with body size and humans are very good at making size judgments based on the acoustic effect of vocal tract length only. Here we investigate the underlying mechanism for processing this main auditory cue to size information in the human brain. Sensory encoding of the acoustic effect of vocal tract length (VTL) depends on a time-stabilized spectral scaling mechanism that is independent of glottal pulse rate (GPR, or voice pitch); we provide evidence that a potential neural correlate for such a mechanism exists in the medial geniculate body (MGB). The perception of the acoustic effect of speaker size is influenced by GPR suggesting an interaction between VTL and GPR processing; such an interaction occurs only at the level of non-primary auditory cortex in planum temporale and anterior superior temporal gyrus. Our findings support a two-stage model for the processing of size information in speech based on an initial stage of sensory analysis as early as MGB, and a neural correlate of the perception of source size in non-primary auditory cortex.

Acoustic Stimulation↗
PubMed2006

Human brain mechanisms for the early analysis of voices.

In this functional magnetic resonance imaging study, we investigated human brain mechanisms that are involved in the analysis of voices as sound sources and in the pre-semantic analysis of voice information. The source of the voice was altered by changing the speaker, and the salience of the voice was altered by changing the amount of spectrotemporal detail. We identified a mechanism for detecting a change in the source of the voice in the posterior superior temporal lobe and anatomically distinct mechanisms for the detailed analysis of voice information in a bilateral network extending from the posterior to the anterior superior temporal lobe surrounding the superior temporal sulcus. The findings are consistent with a processing hierarchy in which general source attributes are analyzed in the posterior superior temporal lobe, abstraction of voice identity features occurs in posterior superior temporal sulcus, and further analysis of voice information occurs in anterior superior temporal sulcus and higher order cortices in the middle and anterior temporal lobe.

Adult↗
PubMed2005

Analysis of the spectral envelope of sounds by the human brain.

Spectral envelope is the shape of the power spectrum of sound. It is an important cue for the identification of sound sources such as voices or instruments, and particular classes of sounds such as vowels. In everyday life, sounds with similar spectral envelopes are perceived as similar: we recognize a voice or a vowel regardless of pitch and intensity variations, and we recognize the same vowel regardless of whether it is voiced (a spectral envelope applied to a harmonic series) or whispered (a spectral envelope applied to noise). In this functional magnetic resonance imaging (fMRI) experiment, we investigated the basis for analysis of spectral envelope by the human brain. Changing either the pitch or the spectral envelope of harmonic sounds produced similar activation within a bilateral network including Heschl's gyrus and adjacent cortical areas in the superior temporal lobe. Changing the spectral envelope of continuously alternating noise and harmonic sounds produced additional right-lateralized activation in superior temporal sulcus (STS). Our findings show that spectral shape is abstracted in superior temporal sulcus, suggesting that this region may have a generic role in the spectral analysis of sounds. These distinct levels of spectral analysis may represent early computational stages in a putative anteriorly directed stream for the categorization of sound.

Adult↗
PubMed2003

Separating pitch chroma and pitch height in the human brain.

Musicians recognize pitch as having two dimensions. On the keyboard, these are illustrated by the octave and the cycle of notes within the octave. In perception, these dimensions are referred to as pitch height and pitch chroma, respectively. Pitch chroma provides a basis for presenting acoustic patterns (melodies) that do not depend on the particular sound source. In contrast, pitch height provides a basis for segregation of notes into streams to separate sound sources. This paper reports a functional magnetic resonance experiment designed to search for distinct mappings of these two types of pitch change in the human brain. The results show that chroma change is specifically represented anterior to primary auditory cortex, whereas height change is specifically represented posterior to primary auditory cortex. We propose that tracking of acoustic information streams occurs in anterior auditory areas, whereas the segregation of sound objects (a crucial aspect of auditory scene analysis) depends on posterior areas.

Acoustic Stimulation↗
PubMed2003

Distinct mechanisms for processing spatial sequences and pitch sequences in the human auditory brain.

Perception of the acoustic world requires the simultaneous processing of the acoustic patterns associated with sound objects and their location in space. In this functional magnetic resonance experiment, we investigated the human brain areas engaged in the analysis of pitch sequences and sequences of acoustic spatial locations in a paradigm in which both could be varied independently. Subjects were presented with sequences of sounds in which the individual sounds were regular interval noises with variable pitch. Positions of individual sounds were varied using a virtual acoustic space paradigm during scanning. Sound sequences with changing pitch specifically activated lateral Heschl's gyrus (HG), anterior planum temporale (PT), planum polare, and superior temporal gyrus anterior to HG. Sound sequences with changing spatial locations specifically activated posteromedial PT. These results demonstrate directly that distinct mechanisms for the analysis of pitch sequences and acoustic spatial sequences exist in the human brain. This functional differentiation is evident as early as PT: within PT, pitch pattern is processed anterolaterally and spatial location is processed posteromedially. These areas may represent human homologs of macaque lateral and medial belt, respectively.

Acoustic Stimulation↗
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↗