Biomedical subjects

J Ashburner

Publications and source records attributed to J Ashburner.

At least 37 records · Page 2Linked to original sources

PubMed2000

Navigation-related structural change in the hippocampi of taxi drivers.

Structural MRIs of the brains of humans with extensive navigation experience, licensed London taxi drivers, were analyzed and compared with those of control subjects who did not drive taxis. The posterior hippocampi of taxi drivers were significantly larger relative to those of control subjects. A more anterior hippocampal region was larger in control subjects than in taxi drivers. Hippocampal volume correlated with the amount of time spent as a taxi driver (positively in the posterior and negatively in the anterior hippocampus). These data are in accordance with the idea that the posterior hippocampus stores a spatial representation of the environment and can expand regionally to accommodate elaboration of this representation in people with a high dependence on navigational skills. It seems that there is a capacity for local plastic change in the structure of the healthy adult human brain in response to environmental demands.

Adult↗

PubMed2000

Image registration using a symmetric prior--in three dimensions.

This paper describes a Bayesian method for three-dimensional registration of brain images. A finite element approach is used to obtain a maximum a posteriori estimate of the deformation field at every voxel of a template volume. The priors used by the MAP estimate penalize unlikely deformations and enforce a continuous one-to-one mapping. The deformations are assumed to have some form of symmetry, in that priors describing the probability distribution of the deformations should be identical to those for the inverses (i.e., warping brain A to brain B should not be different probablistically from warping B to A). A gradient descent algorithm is presented for estimating the optimum deformations.

Algorithms↗

PubMed2000

Characterization and correction of interpolation effects in the realignment of fMRI time series.

Subject motion in functional magnetic resonance imaging (fMRI) studies can be accurately estimated using realignment algorithms. However, residual changes in signal intensity arising from motion have been identified in the data even after realignment of the image time series. The nature of these artifacts is characterized using simulated displacements of an fMRI image and is attributed to interpolation errors introduced by the resampling inherent within realignment. A correction scheme that uses a periodic function of the estimated displacements to remove interpolation errors from the image time series on a voxel-by-voxel basis is proposed. The artifacts are investigated using a brain phantom to avoid physiological confounds. Small- and large-scale systematic displacements show that the artifacts have the same form as revealed by the simulated displacements. A randomly displaced phantom and a human subject are used to demonstrate that interpolation errors are minimized using the correction.

Algorithms↗

PubMed2000

Voxel-based morphometry--the methods.

At its simplest, voxel-based morphometry (VBM) involves a voxel-wise comparison of the local concentration of gray matter between two groups of subjects. The procedure is relatively straightforward and involves spatially normalizing high-resolution images from all the subjects in the study into the same stereotactic space. This is followed by segmenting the gray matter from the spatially normalized images and smoothing the gray-matter segments. Voxel-wise parametric statistical tests which compare the smoothed gray-matter images from the two groups are performed. Corrections for multiple comparisons are made using the theory of Gaussian random fields. This paper describes the steps involved in VBM, with particular emphasis on segmenting gray matter from MR images with nonuniformity artifact. We provide evaluations of the assumptions that underpin the method, including the accuracy of the segmentation and the assumptions made about the statistical distribution of the data.

Brain↗

PubMed2000

Optimization of 3-D MP-RAGE sequences for structural brain imaging.

An optimized MR sequence for structural three-dimensional brain scans is presented, giving good T(1) contrast and excellent white matter/gray matter segmentation. Modification of the usual linear phase encoding order to centric phase encoding restores the contrast loss, which usually occurs after magnetization preparation during the acquisition process when large volumes are imaged. The deleterious effects on the point-spread function are compensated by means of an appropriate k-space filter. RF coil inhomogeneities are corrected by means of shaped excitation pulses. High contrast-to-noise images of the entire brain with 1 mm isotropic resolution can be obtained in 12 min. The contrast-to-noise-ratio is about 100% higher than for sequences based on linear phase encoding.

Anatomy, Cross-Sectional↗

PubMed2000

Representation of the temporal envelope of sounds in the human brain.

The cerebral representation of the temporal envelope of sounds was studied in five normal-hearing subjects using functional magnetic resonance imaging. The stimuli were white noise, sinusoidally amplitude-modulated at frequencies ranging from 4 to 256 Hz. This range includes low AM frequencies (up to 32 Hz) essential for the perception of the manner of articulation and syllabic rate, and high AM frequencies (above 64 Hz) essential for the perception of voicing and prosody. The right lower brainstem (superior olivary complex), the right inferior colliculus, the left medial geniculate body, Heschl's gyrus, the superior temporal gyrus, the superior temporal sulcus, and the inferior parietal lobule were specifically responsive to AM. Global tuning curves in these regions suggest that the human auditory system is organized as a hierarchical filter bank, each processing level responding preferentially to a given AM frequency, 256 Hz for the lower brainstem, 32-256 Hz for the inferior colliculus, 16 Hz for the medial geniculate body, 8 Hz for the primary auditory cortex, and 4-8 Hz for secondary regions. The time course of the hemodynamic responses showed sustained and transient components with reverse frequency dependent patterns: the lower the AM frequency the better the fit with a sustained response model, the higher the AM frequency the better the fit with a transient response model. Using cortical maps of best modulation frequency, we demonstrate that the spatial representation of AM frequencies varies according to the response type. Sustained responses yield maps of low frequencies organized in large clusters. Transient responses yield maps of high frequencies represented by a mosaic of small clusters. Very few voxels were tuned to intermediate frequencies (32-64 Hz). We did not find spatial gradients of AM frequencies associated with any response type. Our results suggest that two frequency ranges (up to 16 and 128 Hz and above) are represented in the cortex by different response types. However, the spatial segregation of these two ranges is not systematic. Most cortical regions were tuned to low frequencies and only a few to high frequencies. Yet, voxels that show a preference for low frequencies were also responsive to high frequencies. Overall, our study shows that the temporal envelope of sounds is processed by both distinct (hierarchically organized series of filters) and shared (high and low AM frequencies eliciting different responses at the same cortical locus) neural substrates. This layout suggests that the human auditory system is organized in a parallel fashion that allows a degree of separate routing for groups of AM frequencies conveying different information and preserves a possibility for integration of complementary features in cortical auditory regions.

Acoustic Stimulation↗

PubMed2000

Learning- and expectation-related changes in the human brain during motor learning.

We have studied a simple form of motor learning in the human brain so as to isolate activity related to motor learning and the prediction of sensory events. Whole-brain, event-related functional magnetic resonance imaging (fMRI) was used to record activity during classical discriminative delay eyeblink conditioning. Auditory conditioned stimulus (CS+) trials were presented either with a corneal airpuff unconditioned stimulus (US, paired), or without a US (unpaired). Auditory CS- trials were never reinforced with a US. Trials were presented pseudorandomly, 66 times each. The subjects gradually produced conditioned responses to CS+ trials, while increasingly differentiating between CS+ and CS- trials. The increasing difference between hemodynamic responses for unpaired CS+ and for CS- trials evolved slowly during conditioning in the ipsilateral cerebellar cortex (Crus I/Lobule HVI), contralateral motor cortex and hippocampus. To localize changes that were related to sensory prediction, we compared trials on which the expected airpuff US failed to occur (Unpaired CS+) with trials on which it occurred as expected (Paired CS+). Error-related signals in the contralateral cerebellum and somatosensory cortex were seen to increase during learning as the sensory prediction became stronger. The changes seen in the ipsilateral cerebellar cortex may be due either to the violations of sensory predictions, or to learning-related increases in the excitability of cerebellar neurons to presentations of the CS+.

Acoustic Stimulation↗

PubMed2000

A voxel-based morphometry study of semantic dementia: relationship between temporal lobe atrophy and semantic memory.

The cortical anatomy of 6 patients with semantic dementia (the temporal lobe variant of frontotemporal dementia) was contrasted with that of a group of age-matched normal subjects by using voxel-based morphometry, a technique that identifies changes in gray matter volume on a voxel-by-voxel basis. Among the circumscribed regions of neuronal loss, the left temporal pole (Brodmann area 38) was the most significantly and consistently affected region. Cortical atrophy in the left hemisphere also involved the inferolateral temporal lobe (Brodmann area 20/21) and fusiform gyrus. In addition, the right temporal pole (Brodmann area 38), the ventromedial frontal cortex (Brodmann area 11/32) bilaterally, and the amygdaloid complex were affected, but no significant atrophy was measured in the hippocampus, entorhinal, or caudal perirhinal cortex. The degree of semantic memory impairment across the 6 cases correlated significantly with the extent of atrophy of the left anterior temporal lobe but not with atrophy in the adjacent ventromedial frontal cortex. These results confirm that the anterior temporal lobe is critically involved in semantic processing, and dissociate its function from that of the adjacent frontal region.

Aged↗

PubMed2000

Detecting bilateral abnormalities with voxel-based morphometry.

In this article we describe a new method, using SPM99, that searches explicitly for bilateral structural abnormalities. Children with bilateral pathology have a poorer prognosis than children with unilateral damage. After brain injury or disease in childhood, it is thought that rescue of function is only possible if the neuronal substrates of that function are preserved and operational in at least one hemisphere [Vargha-Khadem and Mishkin, 1997]. If this is the case, the detection of bilateral abnormalities would greatly facilitate more accurate prognosis in children with brain injury or developmental disorders. We have therefore developed a technique to detect bilateral abnormalities that uses conjunction analysis with voxel based morphometry. It is illustrated using a group of patients with bilateral hypoxic-ischaemic damage to the hippocampus. The approach is shown to have enhanced specificity and sensitivity relative to conventional unilateral characterisations.

Amnesia↗

PubMed1999

The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans.

Autism is a biological disorder which affects social cognition, and understanding brain abnormalities of the former will elucidate the brain basis of the latter. We report structural MRI data on 15 high-functioning individuals with autistic disorder. A voxel-based whole brain analysis identified grey matter differences in an amygdala centered system relative to 15 age- and IQ-matched controls. Decreases of grey matter were found in anterior parts of this system (right paracingulate sulcus, left inferior frontal gyrus). Increases were found in posterior parts (amygdala/peri-amygdaloid cortex, middle temporal gyrus, inferior temporal gyrus), and in regions of the cerebellum. These structures are implicated in social cognition by animal, imaging and histopathological studies. This study therefore provides converging evidence of the physiological basis of social cognition.

Adult↗

PubMed1999

Kallmann's syndrome: mirror movements associated with bilateral corticospinal tract hypertrophy.

OBJECTIVE: To investigate the etiology of mirror movements in patients with X-linked Kallmann's syndrome (xKS) through statistical analysis of pooled white matter data from structural MR images. BACKGROUND: Mirror movements occur in 85% of xKS patients. Previous electrophysiologic studies have suggested an abnormal ipsilateral corticospinal tract projection in xKS patients exhibiting mirror movements. However, an alternative hypothesis has proposed a functional lack of transcallosal inhibitory fibers. METHODS: T1-weighted brain scans were normalized into stereotaxic space with segregation of gray and white matter to allow comparison of pooled white matter data on a voxel-by-voxel basis using SPM-96 software. Nine xKS patients were compared with two age-matched groups of nonmirroring individuals: nine patients with autosomal Kallmann's syndrome (aKS) and nine age-matched normal (healthy) men. RESULTS: Hypertrophy of the corpus callosum was found in both Kallmann's syndrome groups: the anterior and midsection in xKS, and the genu and posterior section in aKS. Bilateral hypertrophy of the corticospinal tract was found only in the group of xKS patients exhibiting mirror movements. SPM analysis was validated by an independent region of interest analysis of corpus callosum size. CONCLUSION: Although morphometry on its own cannot determine the cause of mirror movements, the specific finding of a hypertrophied corticospinal tract in xKS is consistent with electrophysiologic evidence suggesting that mirror movements in xKS result from abnormal development of the ipsilateral corticospinal tract fibers.

Adult↗

PubMed1999

Speed-dependent responses in V5: A replication study.

In a previous paper, we used fMRI to examine motion-sensitive responses in human area V5 as a function of stimulus speed. As predicted by electrophysiological findings, we observed optimal responses at intermediate speeds of around 7 to 30 degrees /s. These results revealed a nonlinear (inverted "U") dependency on speed that was also evident in V3a. In this paper we repeated the experiment using an improved stimulus and a larger range of speeds. We replicated our previous findings and extended our characterization of speed-dependent responses: Optimal responses were seen in V5 at speeds of 4 and 8 degrees /s and in V3a at speeds of 4 to 16 degrees /s. We were also able to show an interaction between speed (fast vs slow) and contrast (color > luminance) in V5. This interaction was anticipated on the basis of the different properties of the geniculate and extrageniculate inputs to V5. Finally, we were also able to demonstrate an interaction between motion (moving vs stationary) and contrast (color > luminance) in V4. This suggests that for V4, color-specific responses are augmented in the context of motion; or equivalently, that color contrast enhances any motion-sensitive responses in V4.

Artifacts↗

PubMed1999

High-dimensional image registration using symmetric priors.

This paper is about warping a brain image from one subject (the object image) so that it matches another (the template image). A high-dimensional model is used, whereby a finite element approach is employed to estimate translations at the location of each voxel in the template image. Bayesian statistics are used to obtain a maximum a posteriori (MAP) estimate of the deformation field. The validity of any registration method is largely based upon the constraints or, in this instance, priors incorporated into the model describing the transformations. In this approach we assume that the priors should have some form of symmetry, in that priors describing the probability distribution of the deformations should be identical to those for the inverses (i.e., warping brain A to brain B should not be different probabilistically from warping B to A). The fundamental assumption is that the probability of stretching a voxel by a factor of n is considered to be the same as the probability of shrinking n voxels by a factor of n(-1). In the Bayesian framework adopted here, the priors are assumed to have a Gibbs form, where the Gibbs potential is a penalty function that embodies this symmetry. The penalty function of choice is based upon the singular values of the Jacobian having a lognormal distribution. This enforces a continuous one-to-one mapping. A gradient descent algorithm is presented that incorporates the above priors in order to obtain a MAP estimate of the deformations. We demonstrate this approach for the two-dimensional case, but the principles can be extended to three dimensions. A number of examples are given to demonstrate how the method works.

Bayes Theorem↗

PubMed1999

The critical relationship between the timing of stimulus presentation and data acquisition in blocked designs with fMRI.

This paper concerns the experimental design and statistical models employed by fMRI activation studies which block presentation of linguistic stimuli. In particular, we note that the relationship between the timing of stimulus presentation and data acquisition can have a substantial impact on the ability to detect activations in critical language areas, even when the stimuli are presented in blocks. Using a blocked word rhyming paradigm and repeated investigations on a single subject, activation was observed in Broca's area (left inferior frontal cortex) and Wernicke's area (left posterior temporoparietal cortex) when (i) the timing of data acquisition was distributed throughout the peristimulus time and (ii) an event-related analysis was used to model the phasic nature of the hemodynamic response within each block of repeated word stimuli. In contrast, when the timing of data acquisition relative to stimulus presentation was fixed, activation was detected in Broca's area but not consistently in Wernicke's area. Our results indicate that phasic responses to stimuli occur even in a blocked design and that the sampling and proper modeling of these responses can have profound effects on their detection. Specifically, distributed sampling over peristimulus time is essential in order to detect small activations particularly when they are transient. These findings are likely to generalize to the detection of transient signals in any cognitive paradigm.

Brain Mapping↗

PubMed1999

Voxel-by-voxel comparison of automatically segmented cerebral gray matter--A rater-independent comparison of structural MRI in patients with epilepsy.

Quantitative evaluation of MRI in patients with epilepsy can give more information than qualitative assessment. Previously developed volume-of-interest-based methods identified subtle widespread structural changes in the neocortex beyond the visualized lesions in patients with malformations of cortical development (MCD) and hippocampal sclerosis (HS) and also in MRI-negative patients with juvenile myoclonic epilepsy (JME). This study evaluates a voxel-based automated analysis of structural MRI in epilepsy. After fully automated segmentation of cerebral gray matter from structural T1-weighted, high-resolution MRI scans, we applied the automated and objective technique of statistical parametric mapping (SPM) to the analysis of gray matter of 35 control subjects, 10 patients with partial seizures and MCD, 10 patients with left temporal lobe epilepsy (TLE) and HS, 10 patients with left TLE and normal MR quantitation of the hippocampus, and 20 patients with JME. At a corrected threshold of P < 0.05, significant abnormalities were found in 3/35 controls; in all 10 patients with MCD, 6 of whom had additional lesions beyond the margins of the visualized abnormalities; in 2/10 TLE patients with HS; in 2/10 MRI-negative TLE; and in 4/20 JME patients. Group comparisons between control subjects and HS patients identified the affected left temporal lobe with an increase in gray matter in the posterior temporal lobe, but did not identify hippocampal atrophy. The group of MRI-negative TLE patients showed no abnormalities compared with control subjects. Group comparison between control subjects and JME patients identified a mesial frontal increase in gray matter. The SPM-based voxel-by-voxel comparison of gray matter distribution identified MCD and abnormalities beyond the visualized lesion in individual MCD patients. The method did not reliably identify HS in individual patients or identify abnormalities in individual MRI-negative patients with TLE or JME in a proportion larger than the chance findings in the control group. Using group comparisons, structural abnormalities in the neocortical gray matter of patients with TLE and HS were lateralized to the affected temporal lobe. In patients with JME as a group, an increase in gray matter was localized to the mesial frontal area, corroborating earlier quantitative MRI findings.

Adolescent↗

PubMed1999

Correlation between structural and functional changes in brain in an idiopathic headache syndrome.

Fundamental to the concept of idiopathic or primary headache, including migraine, tension-type headache and cluster headache, is the currently accepted view that these conditions are due to abnormal brain function with completely normal brain structure. Cluster headache is one such idiopathic headache with many similarities to migraine, including normal brain structure on magnetic resonance imaging and abnormal function in the hypothalamic grey matter by positron emission tomography. Given the consistency of the positron emission tomography findings with the clinical presentation, we sought to assess whether the brains of such patients were structurally normal. We used voxel-based morphometry, an objective and automated method of analyzing changes in brain structure, to study the structure of the brains of patients with cluster headache. We found a co-localization of structural changes and changes in local brain activity with positron emission tomography in the same area of the brain in the same patients. The results indicate that the current view of the neurobiology of cluster headache requires complete revision and that this periodic headache is associated with a hitherto unrecognized brain abnormality in the hypothalamic region. We believe that voxel-based morphometry has the potential to change in the most fundamental way our concept of primary headache disorders, requiring a radical reappraisal of the tenet of structural normality.

Adult↗

PubMed1999

Frontal, midbrain and striatal dopaminergic function in early and advanced Parkinson's disease A 3D [(18)F]dopa-PET study.

We have studied focal changes in dopaminergic function throughout the brain volume in early and advanced Parkinson's disease by applying statistical parametric mapping (SPM) to 3D [(18)F]dopa-PET. Data from seven early hemi-Parkinson's disease and seven advanced bilateral Parkinson's disease patients were compared with that from 12 normal controls. Parametric images of [(18)F]dopa influx rate constant (K(i)(o)) were generated for each subject from dynamic 3D [(18)F]dopa datasets and transformed into standard stereotactic space. Significant changes in mean voxel [(18)F]dopa K(i)(o) values between the normal control group and each Parkinson's disease group were localized with SPM. Conventional region of interest analysis was also applied to comparable regions on the untransformed image datasets. In early left hemi-Parkinson's disease, significant extrastriatal increases in [(18)F]dopa K(i)(o) were observed in the left anterior cingulate gyrus and the dorsal midbrain region (P < 0.05, corrected) along with decreases in striatal [(18)F]dopa K(i)(o). In advanced Parkinson's disease, significant extrastriatal decreases in [(18)F]dopa K(i)(o) were observed in the ventral and dorsal midbrain regions (P < 0.05, corrected). No significant changes in [(18)F]dopa K(i)(o) were observed in the anterior cingulate region. In a direct comparison between the early and late Parkinson's disease groups, we observed relative [(18)F]dopa K(i)(o) reductions in ventral and dorsal midbrain, and dorsal pontine regions along with striatal [(18)F]dopa K(i)(o) reductions. Similiar results were found with a region of interest approach, on non-transformed data, except for the focal midbrain [(18)F]dopa K(i)(o) increase seen in early Parkinson's disease. In conclusion, using SPM with [(18)F]dopa-PET, we have objectively localized changes in extrastriatal, pre-synaptic dopaminergic function in Parkinson's disease. The significance of the increased dopaminergic activity of anterior cingulate in early Parkinson's disease remains unclear, but may be compensatory. The [(18)F]dopa signal in dorsal midbrain and pontine regions suggests that [(18)F]dopa is taken up by serotonergic and noradrenergic neurons which also degenerate in advanced Parkinson's disease. This suggests, therefore, that Parkinson's disease is a monoaminergic neurodegenerative disorder.

Biological Transport↗

PubMed1999

Functional neuroimaging of speech perception in six normal and two aphasic subjects.

This positron emission tomography study used a correlational design to investigate neural activity during speech perception in six normal subjects and two aphasic patients. The normal subjects listened either to speech or to signal-correlated noise equivalents; the latter were nonspeech stimuli, similar to speech in complexity but not perceived as speechlike. Regions common to the auditory processing of both types of stimuli were dissociated from those specific to spoken words. Increasing rates of presentation of both speech and nonspeech correlated with cerebral activity in bilateral transverse gyri and adjacent superior temporal cortex. Correlations specific to speech stimuli were located more anteriorly in both superior temporal sulci. The only asymmetry in normal subjects was a left lateralized response to speech in the posterior superior temporal sulcus, corresponding closely to structural asymmetry on the subjects' magnetic resonance images. Two patients, who had left temporal infarction but performed well on single word comprehension tasks, were also scanned while listening to speech. These cases showed right superior temporal activity correlating with increasing rates of hearing speech, but no significant left temporal activation. These findings together suggest that the dorsolateral temporal cortex of both hemispheres can be involved in prelexical processing of speech.

Adult↗