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Biomedical subjects

Paul M Matthews

Publications and source records attributed to Paul M Matthews.

At least 19 recordsLinked to original sources
PubMed2005

Color of scents: chromatic stimuli modulate odor responses in the human brain.

Color has a profound effect on the perception of odors. For example, strawberry-flavored drinks smell more pleasant when colored red than green and descriptions of the "nose" of a wine are dramatically influenced by its color. Using functional magnetic resonance imaging, we demonstrate a neurophysiological correlate of these cross-modal visual influences on olfactory perception. Subjects were scanned while exposed either to odors or colors in isolation or to color-odor combinations that were rated on the basis of how well they were perceived to match. Activity in caudal regions of the orbitofrontal cortex and in the insular cortex increased progressively with the perceived congruency of the odor-color pairs. These findings demonstrate the neuronal correlates of olfactory response modulation by color cues in brain areas previously identified as encoding the hedonic value of smells.

Adult↗
PubMed2005

Variability in fMRI: a re-examination of inter-session differences.

We revisit a previous study on inter-session variability (McGonigle et al. [2000]: Neuroimage 11:708-734), showing that contrary to one popular interpretation of the original article, inter-session variability is not necessarily high. We also highlight how evaluating variability based on thresholded single-session images alone can be misleading. Finally, we show that the use of different first-level preprocessing, time-series statistics, and registration analysis methodologies can give significantly different inter-session analysis results.

Adult↗
PubMed2005

Category-related activation for written words in the posterior fusiform is task specific.

Category-related brain activations have been reported in the posterior fusiform gyri when people view pictures of tools and animals, but only a single study has observed this pattern when the stimuli were words, rather than pictures. Here we replicate these category effects with words and provide evidence that distinctive patterns of activation are task specific. The results suggest that category-related activation in the posterior fusiform gyri can be driven either "bottom-up" by visual processing of images or "top-down" by word processing.

Adult↗
PubMed2004

New approaches for exploring anatomical and functional connectivity in the human brain.

Information processing in the primate brain is based on the complementary principles of modular and distributed information processing. The former emphasizes the specialization of functions within different brain areas. The latter emphasizes the massively parallel nature of brain networks and the fact that function also emerges from the flow of information between brain areas. The localization of function to specific brain areas ("functional segregation") is the commonest approach to investigating function; however, an emerging, complementary approach ("functional integration") describes function in terms of the information flow across networks of areas. Here, we highlight recent advances in neuroimaging methodology that have made it possible to investigate the anatomical architecture of networks in the living human brain with diffusion tensor imaging (DTI). We also highlight recent thinking on the ways in which functional imaging can be used to characterize information transmission across networks in the human brain (functional and effective connectivity).

Animals↗
PubMed2004

Morphology and the internal structure of words.

Morphology is the aspect of language concerned with the internal structure of words, and languages vary in the extent to which they rely on morphological structure. Consequently, it is not clear whether morphology is a basic element of a linguistic structure or whether it emerges from systematic regularities between the form and meaning of words. Here, we looked for evidence of morphological structure at a neural systems level by using a visual masked priming paradigm and functional MRI. Form and meaning relations were manipulated in a 2 x 2 design to identify reductions in blood oxygenation level-dependent signal related to shared form (e.g., corner-corn), shared meaning (e.g., idea-notion), and shared morphemes (e.g., boldly-bold, which overlapped in both form and meaning). Relative to unrelated pairs (e.g., ozone-hero), morphologically related items reduced blood oxygenation level-dependent signal in the posterior angular gyrus bilaterally, left occipitotemporal cortex, and left middle temporal gyrus. In the posterior angular gyrus, a neural priming effect was observed for all three priming conditions, possibly reflecting reduced attentional demands rather than overlapping linguistic representations per se. In contrast, the reductions seen in the left occipitotemporal cortex and left middle temporal gyrus corresponded, respectively, to main effects of orthographic and semantic overlap. As neural regions sensitive to morphological structure overlapped almost entirely with regions sensitive to orthographic and semantic relatedness, our results suggest that morphology emerges from the convergence of form and meaning.

Adolescent↗
PubMed2004

Functional-anatomical validation and individual variation of diffusion tractography-based segmentation of the human thalamus.

Parcellation of the human thalamus based on cortical connectivity information inferred from non-invasive diffusion-weighted images identifies sub-regions that we have proposed correspond to nuclei. Here we test the functional and anatomical validity of this proposal by comparing data from diffusion tractography, cytoarchitecture and functional imaging. We acquired diffusion imaging data in eleven healthy subjects and performed probabilistic tractography from voxels within the thalamus. Cortical connectivity information was used to divide the thalamus into sub-regions with highest probability of connectivity to distinct cortical areas. The relative volumes of these connectivity-defined sub-regions correlate well with volumetric predictions based on a histological atlas. Previously reported centres of functional activation within the thalamus during motor or executive tasks co-localize within atlas regions showing high probabilities of connection to motor or prefrontal cortices, respectively. This work provides a powerful validation of quantitative grey matter segmentation using diffusion tractography in humans. Co-registering thalamic sub-regions from 11 healthy individuals characterizes inter-individual variation in segmentation and results in a population-based atlas of the human thalamus that can be used to assign likely anatomical labels to thalamic locations in standard brain space. This provides a tool for specific localization of functional activations or lesions to putative thalamic nuclei.

Adult↗
PubMed2004

Accelerated evolution of brain atrophy and "black holes" in MS patients with APOE-epsilon 4.

Apolipoprotein E (APOE)-epsilon4 has been associated with an unfavorable course of multiple sclerosis (MS). The mechanisms responsible for this are unclear, although cross-sectional MRI demonstrated a higher extent of "black holes" (BHs) in such patients. Here, we have studied the impact of the APOE genotype on both the longitudinal evolution of focal (BH ratio) and global (brain volume change [BVC]) brain tissue damage. Ninety-nine MS patients underwent ApoE genotyping, clinical examination, and magnetic resonance imaging at baseline and after 2.7 +/- 1.1 years to assess lesion load (LL) and BVC. In APOE-epsilon4 patients, the annual reduction in brain volume was fivefold higher (-0.65 +/- 0.61%) than in those without APOE-epsilon4 (-0.13 +/- 0.36%; p = 0.0001). At baseline, T(2) LL and T(1) LL were non-significantly higher in epsilon4 carriers, despite a shorter disease duration and absence of significant clinical differences. During follow-up, T(1) LL increased from 1.2 +/- 2.3 ccm to 1.7 +/- 2.7 ccm in the epsilon4 group, although T(2) LL did not change, leading to a significantly higher increase in the BH ratio [(T(1) LL/T(2) LL) x 100] from 5.5 to 12.4% (p = 0.005). BH ratio remained almost constant in non-epsilon4 patients (5.0 vs 5.7%). Accelerated brain tissue loss and a higher proportion of lesions evolving into BH therefore provide magnetic resonance imaging evidence for more pronounced tissue destruction in MS patients with APOE-epsilon4.

Adult↗
PubMed2004

The role of microembolisation in cerebral injury as defined by functional magnetic resonance imaging.

OBJECTIVE: Cerebral injury, in both overt and subtle forms, is common following cardiac surgery. Current methods of assessment, most commonly neuropsychological testing, have several limitations and do not accurately define the anatomical and functional injury that occurs. We have assessed the degree of cerebral injury following on-pump and off-pump cardiac surgery using functional magnetic resonance imaging and correlated this with the severity of microembolism as measured by transcranial Doppler ultrasound. METHODS: Sixteen patients undergoing cardiac surgery (8 off-pump coronary artery bypass grafting (CABG), 4 on-pump CABG and 4 open-heart surgery) underwent functional magnetic resonance imaging of the brain pre-operatively and 4 weeks post-operatively. The functional magnetic resonance images demonstrated brain activation during performance of a verbal working memory paradigm. Each patient had continuous transcranial Doppler monitoring intraoperatively using a recently validated technique (multirange, multifrequency Doppler) that allows rejection of artefacts and separation of gas and solid microemboli. Covariate analysis of pre- and post-operative functional magnetic resonance images was performed to correlate local mean signal intensity change with the extent of gas and solid microembolism. RESULTS: The median number of microemboli was 34 (range 10-176) in the off-pump group, 229 (range 127-314) in the on-pump CABG group, and 1220 (range 874-1261) in the open-heart group (P<0.05). The proportion of solid microemboli was significantly lower in the off-pump group in comparison to the on-pump CABG and open-heart groups (9 vs. 25 vs. 20%, respectively, P<0.01). Comparison of pre- and post-operative functional magnetic resonance images demonstrated an overall reduction in task-associated activation in the post-operative period. However, and paradoxically, in certain specific regions of interest there was an increase in the signal intensity which correlated with the total number of microemboli (r=0.9, P<0.01). CONCLUSIONS: Patients undergoing on-pump surgery have a higher degree of gas and solid microembolism which correlates with post-operative cerebral functional MRI activation. As activation with functional magnetic resonance imaging of the brain is known to be sensitive to a wide range of insults, it may prove to be a useful marker of perioperative cerebral injury that could help in the evaluation of potential cerebroprotective strategies.

Adult↗
PubMed2004

Solid and gaseous cerebral microembolization during off-pump, on-pump, and open cardiac surgery procedures.

BACKGROUND: Neurocognitive dysfunction remains a limitation of cardiac surgery with cardiopulmonary bypass. Intraoperative cerebral microembolization is believed to be one of the most important etiologic factors. Using a new generation of transcranial Doppler ultrasonography, we compared the number and nature of intraoperative microemboli in patients undergoing on-pump and off-pump cardiac surgery procedures. METHODS: Bilateral continuous transcranial Doppler monitoring of the middle cerebral arteries was performed in 45 patients (15 off-pump coronary artery bypass grafting, 15 on-pump coronary artery bypass grafting, and 15 open cardiac procedures). All recordings were performed using a multi-range, multifrequency system to allow both measurement of the number and discrimination of the nature of microemboli in the 3 different groups. RESULTS: The median number (interquartile range) of microemboli in the off-pump coronary artery bypass grafting, on-pump coronary artery bypass grafting, and open procedure groups were 40 (28-80), 275 (199-472), and 860 (393-1321), respectively (P <.01). Twelve percent of microemboli in the off-pump coronary artery bypass grafting group were solid compared with 28% and 22% in the on-pump coronary artery bypass grafting and open procedure groups, respectively (P <.05). In the on-pump groups, 24% of microemboli occurred during cardiopulmonary bypass, and 56% occurred during aortic manipulation (cannulation, decannulation, application, and removal of crossclamp or sideclamp). CONCLUSIONS: Cerebral microembolization is significantly reduced with avoidance of cardiopulmonary bypass. The majority of microemboli occurring during cardiac surgery are gaseous, with a higher proportion of solid microemboli in the on-pump group, and may have a different significance for cerebral injury than solid microemboli. The ability to reliably discriminate gas and solid microemboli may have an important role in the implementation of neuroprotective strategies.

Aged↗
PubMed2004

Advances in functional and structural MR image analysis and implementation as FSL.

The techniques available for the interrogation and analysis of neuroimaging data have a large influence in determining the flexibility, sensitivity, and scope of neuroimaging experiments. The development of such methodologies has allowed investigators to address scientific questions that could not previously be answered and, as such, has become an important research area in its own right. In this paper, we present a review of the research carried out by the Analysis Group at the Oxford Centre for Functional MRI of the Brain (FMRIB). This research has focussed on the development of new methodologies for the analysis of both structural and functional magnetic resonance imaging data. The majority of the research laid out in this paper has been implemented as freely available software tools within FMRIB's Software Library (FSL).

Bayes Theorem↗
PubMed2004

Methamphetamine activates reward circuitry in drug naïve human subjects.

Amphetamines are highly addictive drugs that have pronounced effects on emotional and cognitive behavior in humans. These effects are mediated through their potent dopaminergic agonistic properties. Dopamine has also been implicated in the modulation of responses of the 'reward circuit' in animal and human studies. In this study we use functional magnetic resonance imaging (fMRI) to identify the brain circuitry involved in the psychostimulant effect of methamphetamine in psychostimulant-naïve human subjects. Seven healthy volunteers were scanned in a 3T MR imaging system. They received single-blind intravenous infusions of methamphetamine (0.15 mg/kg), and rated their experience of 'mind-racing' on a button press throughout the experiment. Data were analyzed with statistical parametric mapping methods. Amphetamine administration activated the medial orbitofrontal cortex, the rostral part of the anterior cingulate cortex, and the ventral striatum. Ratings of 'mind-racing' after methamphetamine infusion correlated with activations in the rostral part of the anterior cingulate cortex and in the ventral striatum. In addition, activations in the medial orbitofrontal cortex were independent of motor and related responses involved in making the ratings. These findings indicate that the first administration of a psychostimulant to human subjects activates classical reward circuitry. Our data also support recent hypotheses suggesting a central role for the orbitofrontal cortex in drug reinforcement and the development of addiction.

Adult↗
PubMed2004

An update on neuroimaging of multiple sclerosis.

PURPOSE OF REVIEW: The advent of magnetic resonance imaging provided a powerful tool for monitoring the dynamics of pathological changes in multiple sclerosis, but conventional approaches offer only limited information that is directly relevant to clinical progression. Continued developments of imaging methods and their use for diagnosis, monitoring pathology and understanding disease progression are reviewed here. RECENT FINDINGS: Magnetic resonance imaging is now well established as a clinical test for multiple sclerosis, but the specific ways in which imaging information should best be incorporated into diagnostic criteria are still debated. New data defining the substantial pathology in grey matter, regional variation in the progression of pathology and the relationship between the spatial distribution of pathological changes and symptoms are providing an increasingly compelling description of changes relevant to disability. Molecular-imaging approaches promise much more detailed descriptions. Functional magnetic resonance imaging, which suggests that adaptive functional changes could limit clinical expression of pathology, are providing further clues to the link between measures of pathology and disability. SUMMARY: New data further reinforce the view that pathology relevant to clinical progression of multiple sclerosis can be defined by imaging. A range of biologically more specific markers are becoming available using positron emission tomography, as well as magnetic resonance imaging.

Biomarkers↗
PubMed2004

Left inferior prefrontal cortex activity reflects inhibitory rather than facilitatory priming.

Functional neuroimaging has demonstrated reduced activation correlated with behavioral priming effects, a finding generally interpreted in terms of facilitated retrieval of target items in the context of related primes. Without a neutral prime, however, one cannot separate facilitatory effects of related primes from inhibitory effects of unrelated primes. Here we report an auditory semantic priming paradigm with congruent (''The boy bounced the BALL''), neutral (''The next item is BALL''), and incongruent (''Pasta is my favorite kind of BALL'') sentence trials. As previously reported, reduced left inferior prefrontal cortex activation was observed for congruent relative to incongruent trials; however, the neutral condition allowed us to show that the effect arose from increased activation in the incongruent condition rather than reduced activation for congruent trials. Our results suggest that the left inferior prefrontal cortex inhibits interference from prepotent representations in order to select a task-appropriate target, and is consistent with its broader role in behavioral inhibition.

Adolescent↗
PubMed2004

Increased brain GABA concentrations following acute administration of a selective serotonin reuptake inhibitor.

OBJECTIVE: The authors used magnetic resonance spectroscopy (MRS) to assess the effect of acute administration of the selective serotonin reuptake inhibitor (SSRI) citalopram on cortical levels of gamma-aminobutyric acid (GABA). METHOD: Ten healthy volunteers received either intravenous citalopram (10 mg) or saline in a randomized, double-blind, crossover design. The occipital GABA/creatine ratio was measured with a proton MR spectral editing technique. RESULTS: In comparison with saline, citalopram produced a mean increase of 35% in relative brain GABA concentration in the occipital cortex. CONCLUSIONS: These findings extend previous work showing that SSRI treatment increases cortical GABA in depressed patients and suggest that this results from an action of SSRIs on GABA neurons rather than as a secondary consequence of mood improvement.

Adult↗
PubMed2003

Functional asymmetry for auditory processing in human primary auditory cortex.

Structural asymmetries in the supratemporal plane of the human brain are often cited as the anatomical basis for the lateralization of language predominantly to the left hemisphere. However, similar asymmetries are found for structures mediating earlier events in the auditory processing stream, suggesting that functional lateralization may occur even at the level of primary auditory cortex. We tested this hypothesis using functional magnetic resonance imaging to evaluate human auditory cortex responses to monaurally presented tones. Relative to silence, tones presented separately to either ear produced greater activation in left than right Heschl's gyrus, the location of primary auditory cortex. This functional lateralization for primary auditory cortex is distinct from the contralateral dominance reported for other mammals, including nonhuman primates, and may have contributed to the evolution of a unique role for the left hemisphere in language processing.

Adult↗
PubMed2003

Potentially adaptive functional changes in cognitive processing for patients with multiple sclerosis and their acute modulation by rivastigmine.

One explanation for the weak relationship between neuropsychological deficits and conventional measures of disease burden in multiple sclerosis is that brain 'plasticity' allows adaptive reorganization of cognitive functions to limit impairment, despite injury. We have tested this hypothesis. Ten patients with multiple sclerosis and 11 healthy controls were studied using a functional MRI (fMRI) counting Stroop task. The two subject groups had comparable performances, but a predominantly left medial prefrontal region [Brodmann area (BA) 8/9/10] was more active during the task in patients than in controls (corrected P < 0.001), while a right frontal region (including BA 45 and the basal ganglia) was more active in controls than in patients (corrected P = 0.004). The magnitude of the differences correlated with the normalized brain parenchymal volume, a measure of disease burden (r = -0.72, P = 0.02). We then tested the effects of acute administration of rivastigmine, a central cholinesterase inhibitor, on patterns of brain activation. In five out of five multiple sclerosis patients there was a relative normalization of the abnormal Stroop-associated brain activation, although no change in the patterns of brain activation was found in any of four healthy controls given the drug and tested in the same way. We suggest that recruitment of medial prefrontal cortex is a form of adaptive brain plasticity that compensates, in part, for relative deficits in processing related to the reduced right prefrontal cortex activity with multiple sclerosis. This functional plasticity is modulated by cholinergic agonism and must arise from potentially highly dynamic mechanisms such as the 'unmasking' of latent pathways.

Adult↗
PubMed2003

Semantic processing in the left inferior prefrontal cortex: a combined functional magnetic resonance imaging and transcranial magnetic stimulation study.

The involvement of the left inferior prefrontal cortex (LIPC) in phonological processing is well established from both lesion-deficit studies with neurological patients and functional neuroimaging studies of normals. Its involvement in semantic processing, on the other hand, is less clear. Although many imaging studies have demonstrated LIPC activation during semantic tasks, this may be due to implicit phonological processing. This article presents two experiments investigating semantic functions in the LIPC. Results from a functional magnetic resonance imaging experiment demonstrated that both semantic and phonological processing activated a common set of areas within this region. In addition, there was a reliable increase in activation for semantic relative to phonological decisions in the anterior LIPC while the opposite comparison (phonological vs. semantic decisions) revealed an area of enhanced activation within the posterior LIPC. A second experiment used transcranial magnetic stimulation (TMS) to temporarily interfere with neural information processing in the anterior portion of the LIPC to determine whether this region was essential for normal semantic performance. Both repetitive and single pulse TMS significantly slowed subjects' reactions for the semantic but not for the perceptual control task. Our results clarify the functional anatomy of the LIPC by demonstrating that anterior and posterior regions contribute to both semantic and phonological processing, albeit to different extents. In addition, the findings go beyond simply establishing a correlation between semantic processing and activation in the LIPC and demonstrate that a transient disruption of processing selectively interfered with semantic processing.

Adult↗