Biomedical subjects

R S Frackowiak

Publications and source records attributed to R S Frackowiak.

At least 37 records · Page 2Linked to original sources

PubMed2000

The neural correlates of 'deaf-hearing' in man: conscious sensory awareness enabled by attentional modulation.

Attentional modulation of normal sensory processing has a two-fold impact on human brain activity: activation of a network of localized brain regions is associated with paying attention, and activation of specific sensory regions is enhanced relative to passive stimulation. The mechanisms underlying attentional modulation of perception in patients with lesions of sensory cortices are less well understood. Here we report a unique patient suffering from extensive bilateral destruction of the auditory cortices (including the primary auditory fields) who demonstrated conscious perception of the onset and offset of sounds only when selectively attending to the auditory modality. This is the first description of such an attentively modulated 'deaf-hearing' phenomenon and its neural correlates, using H(2)(15)O-PET. Increases in cerebral blood flow associated with conscious awareness of sound that was achieved by listening attentively (compared with identical auditory stimulation presented when the patient was inattentive) were found bilaterally in the lateral (pre)frontal cortices, the spared middle temporal cortices and the cerebellar hemispheres. We conclude that conscious awareness of sounds may be achieved in the absence of the primary auditory cortex, and that selective, 'top-down' attention, associated with prefrontal systems, exerts a crucial modulatory effect on auditory perception within the remaining auditory system.

Acoustic Stimulation↗

PubMed2000

Differential recruitment of the speech processing system in healthy subjects and rehabilitated cochlear implant patients.

Differences in cerebral activation between control subjects and post-lingually deaf rehabilitated cochlear implant patients were identified with PET under various speech conditions of different linguistic complexity. Despite almost similar performance in patients and controls, different brain activation patterns were elicited. In patients, an attentional network including prefrontal and parietal modality-aspecific attentional regions and subcortical auditory regions was over-activated irrespective of the nature of the speech stimuli and during expectancy of speech stimuli. A left temporoparietal semantic region was responsive to meaningless stimuli (vowels). In response to meaningful stimuli (words, sentences, story), left middle and inferior temporal semantic regions and posterior superior temporal phonological regions were under-activated in patients, whereas anterior superior temporal phonological regions were over-activated. These differences in the recruitment of the speech comprehension system reflect the alternative neural strategies that permit speech comprehension after cochlear implantation.

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↗

PubMed1999

A blueprint for movement: functional and anatomical representations in the human motor system.

Despite a clear somatotopic organization of the motor cortex, a movement can be learned with one extremity and performed with another. This suggests that there exists a limb-independent coding for movements. To dissociate brain regions coding for movement parameters from those relevant to the chosen effector, subjects wrote their signature with their dominant index finger and ipsilateral big toe, and we determined those areas activated by both conditions using functional magnetic resonance imaging. The results show that movement parameters for this highly trained movement are stored in secondary sensorimotor cortices of the extremity with which it is usually performed, i.e., the dominant hand, including dorsal and ventral lateral premotor cortices. These areas can be accessed by the foot and are therefore functionally independent from the primary representation of the effector. Thus, somatotopy in secondary structures in the human motor system seems to be defined functionally, and not on the basis of anatomical representations.

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

Rapid assessment of regional cerebral metabolic abnormalities in single subjects with quantitative and nonquantitative [18F]FDG PET: A clinical validation of statistical parametric mapping.

The [18F]fluorodeoxyglucose ([18F]FDG) method for measuring brain metabolism has not the wide clinical application that one might expect, partly because of its high cost and the complexity of the quantification procedure, but also because of reporting techniques based on region of interest (ROI) analysis, which are time-consuming and not fully objective. In this paper we report a clinical validation of statistical parametric mapping (SPM) using rCMRglc (quantitative) and radioactivity distribution (nonquantitative) [18F]FDG PET data. We show that a 10-min noninteractive voxel-based SPM analysis on a standard workstation enables objective assessment, including localization in stereotactic space, of regional glucose consumption abnormalities, whose reliability can be assessed on statistical and clinical grounds. Clinical validity was established using a small series of patients with degenerative or developmental disorders, including probable Alzheimer's disease, progressive aphasia, multiple sclerosis, developmental specific language impairment, and epilepsy. Analysis of quantitative and nonquantitative data showed the same pattern of results, suggesting that, for clinical purposes, quantitation and invasive arterial cannulation can be avoided. This should facilitate a wider application of the technique and the extension of SPM clinical analysis to H215O PET or high resolution SPECT perfusion studies.

Adolescent↗

PubMed1999

Intracranial vessels in trigeminal transmitted pain: A PET study.

The underlying principle in interpreting data from positron emission tomography (PET) is that increases and decreases of synaptic activity in the brain are accompanied by equivalent changes in regional blood flow. However, given the relatively low spatial resolution of PET, regional indices of neural activity can be influenced by signals from nonneural elements in the intracranial space. We have used PET to study the functional neuroanatomy of headache syndromes, such as cluster headache and experimental headache, by observing activation in brain that is due to synaptic activity. In these studies we noted a bilateral activation in midline structures over several planes that, based on its anatomy, is likely to arise from bilateral large intracranial arteries in the region of the cavernous sinus. We have observed this activity in two different group studies and in 11 of 17 single-subject studies. The most likely explanation for this "activation" is the increased volume of space occupied by dilated large vessels containing H215O. We further defined the anatomy of the PET findings using magnetic resonance angiography, which showed bilateral vasodilatation of the internal carotid artery and the basilar artery in nitroglycerin-induced cluster headache attacks. While the fact that vascular structures can contaminate PET-based blood flow studies may be well known to methodological experts, the issue is less well recognized outside the immediate field.

Adult↗

PubMed1999

Emission tomography contribution to clinical neurology.

The role of functional neuroimaging techniques in furthering the understanding of pathophysiological mechanisms of neurological diseases and in the assessment of neurological patients is increasingly important. Here, we review data mainly from emission tomography techniques, namely positron emission tomography (PET) and single photon emission computerized tomography (SPECT), that have helped elucidate the pathophysiology of a number of neurological diseases and have suggested strategies in the treatment of neurological patients. We also suggest possible future developments of functional neuroimaging applied to clinical populations and briefly touch on the emerging role of functional magnetic resonance imaging (fMRI) in clinical neurology and neurosurgery.

Brain↗

PubMed1999

The distribution of cerebral activity related to visuomotor coordination indicating perceptual and executional specialization.

The distribution of increased regional cerebral blood flow (rCBF) related to visuomotor coordination was studied by means of positron emission tomography (PET) in normal subjects. An experimental condition, in which a vertically presented zigzag figure had to be copied in a horizontal orientation, was compared with a control condition in which the same horizontal drawing was made, guided by a horizontally presented example. Cognitive components dealing with the mismatch in visual orientation resulted in activation of (i) right dorsal premotor cortex, (ii) right posterior parietal cortex, (iii) visual cortex (area V1) and (iv) left fusiform gyrus. In a second experiment, conditions were compared in which the same horizontal zigzag figure was copied in either a vertical or a horizontal orientation. Now, the motor components of the transformation of orientation appeared to be associated only with left premotor cortex activation. The differential distribution of activations is regarded to reflect the selective effort to cope with either the visual or the motor component of spatial incongruity, and indicates specialization for perceptual and executive components in visuomotor control. We propose that the perceptual component of visuomotor transformation in our experiment relates to a realignment of the coordinates of a percept to an internally defined coordinate system. The executive component relates to guidance of movement within an internal representation of space. In a preceding behavioural experiment, a majority of patients with Parkinson's disease (PD) failed on the task in which they had to make a horizontal copy of a vertically presented picture. This finding may suggest a deficit in the maintenance of an internal spatial representation to guide movement.

Adolescent↗

PubMed1999

The impact of brain imaging technology on our understanding of motor function and dysfunction.

Brain imaging techniques have demonstrated functional specialisation of multiple areas within the motor system. They have also defined the patterns of interactions between these regions during normal motor function and in motor disorders. Functional imaging makes visible the changes in cortical activity that take place over time during motor functions, from the activations a fraction of a second before voluntary action to cortical neuronal plasticity several weeks after injury. Recently, the functional abnormalities underlying various acquired and developmental motor disorders have been described, as well as the effects of therapeutic intervention.

Brain↗

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

Activation of reward circuitry in human opiate addicts.

The neurobiological mechanisms of opiate addictive behaviour in humans are unknown. A proposed model of addiction implicates ascending brainstem neuromodulatory systems, particularly dopamine. Using functional neuroimaging, we assessed the neural response to heroin and heroin-related cues in established opiate addicts. We show that the effect of both heroin and heroin-related visual cues are maximally expressed in the sites of origin of ascending midbrain neuromodulatory systems. These context-specific midbrain activations predict responses to salient visual cues in cortical and subcortical regions implicated in reward-related behaviour. These findings implicate common neurobiological processes underlying drug and drug-cue-related effects.

Adult↗

PubMed1999

The neural consequences of conflict between intention and the senses.

Normal sensorimotor states involve integration of intention, action and sensory feedback. An example is the congruence between motor intention and sensory experience (both proprioceptive and visual) when we move a limb through space. Such goal-directed action necessitates a mechanism that monitors sensorimotor inputs to ensure that motor outputs are congruent with current intentions. Monitoring in this sense is usually implicit and automatic but becomes conscious whenever there is a mismatch between expected and realized sensorimotor states. To investigate how the latter type of monitoring is achieved we conducted three fully factorial functional neuroimaging experiments using PET measures of relative regional cerebral blood flow with healthy volunteers. In the first experiment subjects were asked to perform Luria's bimanual co-ordination task which involves either in-phase (conditions 1 and 3) or out-of-phase (conditions 2 and 4) bimanual movements (factor one), while looking towards their left hand. In half of the conditions (conditions 3 and 4) a mirror was used that altered visual feedback (factor two) by replacing their left hand with the mirror image of their right hand. Hence (in the critical condition 4) subjects saw in-phase movements despite performing out-of-phase movements. This mismatch between intention, proprioception and visual feedback engendered cognitive conflict. The main effect of out-of-phase movements was associated with increased neural activity in posterior parietal cortex (PPC) bilaterally [Brodmann area (BA) 40, extending into BA 7] and dorsolateral prefrontal cortex (DLPFC) bilaterally (BA 9/46). The main effect of the mirror showed increased neural activity in right DLPFC (BA 9/ 46) and right superior PPC (BA 7) only. Analysis of the critical interaction revealed that the mismatch condition led to a specific activation in the right DLPFC alone (BA 9/46). Study 2, using an identical experimental set-up but manipulating visual feedback from the right hand (instead of the left), subsequently demonstrated that this right DLPFC activation was independent of the hand attended. Finally, study 3 removed the motor intentional component by moving the subjects' hand passively, thus engendering a mismatch between proprioception and vision only. Activation in the right lateral prefrontal cortex was now more ventral than in studies 1 or 2 (BA 44/45). A direct comparison of studies 1 and 3 (which both manipulated visual feedback from the left hand) confirmed that a ventral right lateral prefrontal region is primarily activated by discrepancies between signals from sensory systems, while a more dorsal area in right lateral prefrontal cortex is activated when actions must be maintained in the face of a conflict between intention and sensory outcome.

Adult↗

PubMed1999

Cortical and subcortical control of tongue movement in humans: a functional neuroimaging study using fMRI.

We have used voluntary tongue contraction to test whether we can image activation of the hypoglossal nuclei within the human brain stem by using functional magnetic resonance imaging (fMRI). Functional images of the whole brain were acquired in eight subjects by using T2-weighted echo planar imaging (blood oxygen level development) every 6.2 s. Sequences of images were acquired during 12 periods of 31-s "isometric" rhythmic tongue contraction alternated with 12 periods of 31-s tongue relaxation. Noise arising from cardiac- and respiratory-related movement was removed either by filtration (high pass; cutoff 120 s) or by inclusion in the statistical analysis as confounding effects of no interest. For the group, tongue contraction was associated with significant signal increases (P < 0.05 corrected for multiple comparisons) in the sensorimotor cortex, supplementary motor area, operculum, insula, thalamus, and cerebellum. For the group and for six of eight individuals, significant signal increases were also seen within the medulla (P < 0.001, predefined region of interest with no correction for multiple comparisons); this signal is most likely to reflect neuronal activation associated with the hypoglossal motor nuclei. The data demonstrate that fMRI can be used to detect, simultaneously, the cerebral and brain stem control of tongue movement.

Adult↗

PubMed1998

Human brain activity during spontaneously reversing perception of ambiguous figures.

Looking at ambiguous figures results in rivalry with spontaneous alternation between two percepts. Using event-related functional magnetic resonance imaging, we localized transient human brain activity changes during perceptual reversals. Activation occurred in ventral occipital and intraparietal higher-order visual areas, deactivation in primary visual cortex and the pulvinar. Thus, without any physical stimulus changes, salient perceptual flips briefly engage widely separated specialized cortical areas, but are also associated with intermittent activity breakdown in structures putatively maintaining perceptual stability. Together, the dynamics of integrative perceptual experience are reflected in rapid spatially differentiated activity modulation within a cooperative set of neural structures.

Brain↗

PubMed1998

Neural basis of an inherited speech and language disorder.

Investigation of the three-generation KE family, half of whose members are affected by a pronounced verbal dyspraxia, has led to identification of their core deficit as one involving sequential articulation and orofacial praxis. A positron emission tomography activation study revealed functional abnormalities in both cortical and subcortical motor-related areas of the frontal lobe, while quantitative analyses of magnetic resonance imaging scans revealed structural abnormalities in several of these same areas, particularly the caudate nucleus, which was found to be abnormally small bilaterally. A recent linkage study [Fisher, S., Vargha-Khadem, F., Watkins, K. E., Monaco, A. P. & Pembry, M. E. (1998) Nat. Genet. 18, 168-170] localized the abnormal gene (SPCH1) to a 5. 6-centiMorgan interval in the chromosomal band 7q31. The genetic mutation or deletion in this region has resulted in the abnormal development of several brain areas that appear to be critical for both orofacial movements and sequential articulation, leading to marked disruption of speech and expressive language.

Brain↗

PubMed1998

Hypothalamic activation in cluster headache attacks.

BACKGROUND: Cluster headache, one of the most severe pain syndromes in human beings, is usually described as a vascular headache. However, the striking circadian rhythmicity of this strictly half-sided pain syndrome cannot be readily explained by the vascular hypothesis. We aimed to assess changes in regional cerebral blood flow (rCBF) in patients with cluster headache. METHODS: We used positron emission tomography (PET) to assess the changes in rCBF, as an index of synaptic activity, during nitroglycerin-induced cluster headache attacks in nine patients who had chronic cluster headache. Eight patients who had cluster headache but were not in the bout acted as a control group. FINDINGS: In the acute pain state, activation was seen in the ipsilateral inferior hypothalamic grey matter, the contralateral ventroposterior thalamus, the anterior cingulate cortex, and bilaterally in the insulae. Activation in the hypothalamus was seen solely in the pain state and was not seen in patients who have cluster headache but were out of the bout. INTERPRETATION: Our findings establish central nervous system dysfunction in the region of the hypothalamus as the primum movens in the pathophysiology of cluster headache. We suggest that a radical reappraisal of this type of headache is needed and that it should in general terms, be regarded as a neurovascular headache, to give equal weight to the pathological and physiological mechanisms that are at work.

Adult↗

PubMed1998

Knowing where and getting there: a human navigation network.

The neural basis of navigation by humans was investigated with functional neuroimaging of brain activity during navigation in a familiar, yet complex virtual reality town. Activation of the right hippocampus was strongly associated with knowing accurately where places were located and navigating accurately between them. Getting to those places quickly was strongly associated with activation of the right caudate nucleus. These two right-side brain structures function in the context of associated activity in right inferior parietal and bilateral medial parietal regions that support egocentric movement through the virtual town, and activity in other left-side regions (hippocampus, frontal cortex) probably involved in nonspatial aspects of navigation. These findings outline a network of brain areas that support navigation in humans and link the functions of these regions to physiological observations in other mammals.

Brain Mapping↗