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R Frackowiak

Publications and source records attributed to R Frackowiak.

At least 19 recordsLinked to original sources

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↗

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↗

Identifying global anatomical differences: deformation-based morphometry.

The aim of this paper is to illustrate a method for identifying macroscopic anatomical differences among the brains of different populations of subjects. The method involves spatially normalizing the structural MR images of a number of subjects so that they all conform to the same stereotactic space. Multivariate statistics are then applied to the parameters describing the estimated nonlinear deformations that ensue. To illustrate the method, we compared the gross morphometry of male and female subjects. We also assessed brain asymmetry, the effect of handedness, and interactions among these effects.

Adult↗

Two modulatory effects of attention that mediate object categorization in human cortex.

Attentional modulation of cortical activity was examined by varying the rate of visual stimuli in object categorization tasks according to single and conjoined features. Activation of dorsolateral frontal cortex was independent of the stimulus presentation rate and elicited by the participant's attention to conjoined compared with single features. Several cortical regions showed attentionally modulated activity. In inferior temporal cortex, modulation was due to an additional bias signal underlying normal rate-correlated activity. In two other regions (premotor cortex and cerebellum), attention modified the correlation of activity and the stimulus presentation rate. Attentional effects in the human cortex are expressed by at least two physiologically distinct mechanisms acting on spatially distributed areas.

Adult↗

Changes in cerebral activity pattern due to subthalamic nucleus or internal pallidum stimulation in Parkinson's disease.

High-frequency electrical stimulation of the internal pallidum (GPi) or the subthalamic nucleus (STN) improves clinical symptoms of Parkinson's disease. In 12 parkinsonian patients, 6 with STN and 6 with GPi stimulators, we used H2(15)O positron emission tomography to evaluate whether changes in movement performance were accompanied by change in regional cerebral blood flow (rCBF). Patients were scanned both at rest and while performing a free-choice joystick movement, under conditions of effective and ineffective electrostimulation. During effective STN stimulation, movement-related increases in rCBF were significantly higher in supplementary motor area, cingulate cortex, and dorsolateral prefrontal cortex (DLPFC) than during ineffective stimulation. No significant change was observed in any of these areas during GPi stimulation. The difference between the effect of STN and GPi stimulation on movement-related activity was mainly localized to DLPFC. These results confirm the dominant role of nonprimary motor areas in the control of movement in parkinsonian patients and demonstrate the importance of STN input in the control of these areas.

Electric Stimulation↗

'Theory of mind' in the brain. Evidence from a PET scan study of Asperger syndrome.

The ability to attribute mental states to others ('theory of mind') pervades normal social interaction and is impaired in autistic individuals. In a previous positron emission tomography scan study of normal volunteers, performing a 'theory of mind' task was associated with activity in left medial prefrontal cortex. We used the same paradigm in five patients with Asperger syndrome, a mild variant of autism with normal intellectual functioning. No task-related activity was found in this region, but normal activity was observed in immediately adjacent areas. This result suggests that a highly circumscribed region of left medial prefrontal cortex is a crucial component of the brain system that underlies the normal understanding of other minds.

Adult↗

[Cognitive neuroanatomy of language: contribution of functional cerebral imaging].

This review summarizes the main results obtained to date, concerning the issue of brain/language relationships, from studies using the modern techniques of in vivo functional imaging of the brain, namely Positron Emission Tomography (PET) and, to a lesser extent, the still experimental method of functional Magnetic Resonance Imaging. These studies mostly rely on the so-called cognitive activation paradigm, which consists of recording blood flow variations as measured in PET in normal volunteers during various linguistic tasks compared to reference tasks. Since the late 80's, a great deal of literature has been accumulating, including studies of various aspects of language functions: perceptual (auditory and visual) processing of linguistic materials, expression, verbal memory, semantics... The first few results obtained have already led to challenge some previously widely held dogmas, derived from classical anatomo-clinical studies, such as the role of Wernicke's area in verbal comprehension and the role of Broca's area in language production. The involvement of the left supramarginal gyrus in some aspects of phonological processing has been directly demonstrated. At the same time, some studies have yielded unexpected results suggesting, for instance, a special role for the inferior lateral parts of the left frontal lobe in semantic and/or voluntary aspects of language processing and episodic verbal memory. Among other studies, those concerning the mechanisms of verbal short-term memory have provided interesting parallels with cognitive models. The demonstration, under certain experimental conditions, of an involvement of hitherto unsuspected cortical regions (such as the insular or the temporopolar cortices) is of potential considerable importance. Finally, with current technical improvements of the imaging methods, it will be shortly possible to take into account the important issue of interindividual variations as well as to perform activation studies in brain-damaged patients.

Brain↗

Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson's disease.

Two patients with idiopathic Parkinson's disease (Patients 3 and 4 in our series) were followed up to 3 years after grafting of human embryonic dopamine-rich mesencephalic tissue unilaterally into the putamen. During the first postoperative year both patients showed significant amelioration of parkinsonian symptoms and increased 6-L-[18F]-fluorodopa uptake in the grafted putamen, as assessed with positron emission tomography. Three years after grafting the patients still exhibited increased fluorodopa uptake in the grafted putamen and significant clinical improvements, evidenced by a reduction of the severity of symptoms and of the time spent in the "off" phase, and by a prolongation of the effect of a single dose of L-dopa. Between 1 and 3 years after surgery, Patient 3 showed only minor changes of parkinsonian symptoms on the side contralateral to the graft, whereas there was a worsening on the ipsilateral side. Fluorodopa uptake decreased in the nongrafted putamen but was unchanged in the grafted putamen. Patient 4 continued to improve after the first postoperative year and L-dopa was withdrawn after 32 months. The reduction of parkinsonian symptoms on the side contralateral to the graft became more pronounced between 1 and 3 years after surgery. Fluorodopa uptake further increased in the grafted putamen, whereas no change was detected on the non-grafted side. These results indicate that grafts of embryonic dopamine neurons can survive, grow, and exert functional effects up to at least 3 years after surgery in the parkinsonian brain, despite an ongoing disease process leading to degeneration of the intrinsic dopamine system.

Brain Tissue Transplantation↗

Detection of thirty-second cognitive activations in single subjects with positron emission tomography: a new low-dose H2(15)O regional cerebral blood flow three-dimensional imaging technique.

Positron emission tomography regional CBF (rCBF) studies of cognitive processes have traditionally required 30-60 mCi of H2(15)O per scan and intersubject averaging to achieve statistical significance. However, intersubject anatomical, functional, and disease variability can make such an approach problematic. A new method that produces significant results in single subjects is presented. It is based upon high-sensitivity three-dimensional imaging and a "slow" bolus administration of < 15 mCi of H2(15)O per scan. The method is validated in four normal volunteers using control and auditory-language activation tasks with four scans per condition and statistical parametric mapping analysis. It is demonstrated that the rCBF distribution associated with the cognitive state is detected during the arrival of radiotracer in the brain. This occurs over 30 s and constitutes a critical temporal window during which stimulation should be performed. A 90-s acquisition time is found to produce results of greater significance than a 60-s acquisition time. The implications of the results and the functional neuroanatomical findings are discussed. This method is suitable for the study of individual functional neuroanatomy in many neuropsychological, pharmacologic, and symptom states in normal subjects and in patients with psychiatric and neurologic disorders.

Adult↗

Thalamic stimulation and suppression of parkinsonian tremor. Evidence of a cerebellar deactivation using positron emission tomography.

Parkinsonian tremor can be abolished by chronic high frequency thalamic stimulation of the ventral intermediate nucleus. We have studied six patients with unilateral Parkinson's disease. The patients had an electrode chronically implanted in the ventral intermediate nucleus of the thalamus. We measured changes in cerebral activity by positron emission tomography using an index of regional cerebral blood flow (rCBF). Each patient was scanned in three states: (i) tremor without stimulation (condition A); (ii) tremor with ineffective stimulation (condition B); (iii) tremor abolished by effective stimulation (condition C). The suppression of tremor (C compared with B) was specifically associated with a decrease of rCBF in the cerebellum, whereas the ineffective stimulation (B compared with A) induced a decrease of rCBF in homolateral cerebral cortex. The results give evidence for different contributions from cortex and cerebellum to the generation of parkinsonian tremor and suggest that tremor suppression is mainly associated with a decrease of synaptic activity in the cerebellum.

Aged↗

Regional response differences within the human auditory cortex when listening to words.

The relationship between activity within the human auditory cortices and the presentation rate of heard words was investigated by measuring changes in regional cerebral blood flow with positron emission tomography. We demonstrate that in the primary auditory cortices and middle regions of the superior temporal gyri there is a linear relationship between the rate of presentation of heard words and blood flow response. In contrast, the blood flow response in an area of the left posterior superior temporal gyrus (Wernicke's area) is primarily dependent on the occurrence of words irrespective of their rate of presentation. The primary auditory cortices are associated with the early processing of complex acoustic signals whereas Wernicke's area is associated with the comprehension of heard words. This study demonstrates for the first time that time dependent sensory signals (heard words) detected in the primary auditory cortices are transformed into a time invariant output which is channelled to a functionally specialised region--Wernicke's area. Wernicke's area is therefore distinguished from other areas of the auditory cortex by direct observation of signal transformation rather than by association with a specific behavioural task.

Adult↗

Transplantation of fetal dopamine neurons in Parkinson's disease: one-year clinical and neurophysiological observations in two patients with putaminal implants.

Ventral mesencephalic tissue from aborted human fetuses (age, 6-7 weeks' postconception) was implanted unilaterally into the putamen using stereotaxic surgery in 2 immunosuppressed patients (Patients 3 and 4 in our series) with advanced idiopathic Parkinson's disease. Tissue from 4 fetuses was grafted to each patient. Compared with our previous 2 patients, the following changes in the grafting procedure were introduced: the implantation instrument was thinner, more tissue was placed in the operated structure, and the time between abortion and grafting was shorter. There were no postoperative complications. Both patients showed a gradual and significant amelioration of parkinsonian symptoms (most marked in Patient 3) starting at 6 and 12 weeks after grafting, respectively, reaching maximum stability at approximately 4 to 5 months; patients remained relatively stable thereafter during the 1-year follow-up period. Clinical improvement was observed as a reduction of the time spent in the "off" phase and the number of daily "off" periods; a lessening of bradykinesia and rigidity during the "off" phase, mainly but not solely on the side contralateral to the graft; and a prolongation and change in the pattern of the effect of a single dose of L-dopa. Neurophysiological measurements revealed a more rapid performance of simple and complex arm and hand movements bilaterally, but primarily contralateral to the graft. The results indicate that patients with Parkinson's disease can show significant and sustained improvement of motor function after intrastriatal implantation of fetal dopamine-rich mesencephalic tissue. The accompanying paper by Sawle and colleagues describes the results of repeated positron emission tomography scans in these patients.

Combined Modality Therapy↗

The anatomy of phonological and semantic processing in normal subjects.

We assessed brain activation of nine normal right-handed volunteers in a positron emission tomography study designed to differentiate the functional anatomy of the two major components of auditory comprehension of language, namely phonological versus lexico-semantic processing. The activation paradigm included three tasks. In the reference task, subjects were asked to detect rising pitch within a series of pure tones. In the phonological task, they had to monitor the sequential phonemic organization of non-words. In the lexico-semantic task, they monitored concrete nouns according to semantic criteria. We found highly significant and different patterns of activation. Phonological processing was associated with activation in the left superior temporal gyrus (mainly Wernicke's area) and, to a lesser extent, in Broca's area and in the right superior temporal regions. Lexico-semantic processing was associated with activity in the left middle and inferior temporal gyri, the left inferior parietal region and the left superior prefrontal region, in addition to the superior temporal regions. A comparison of the pattern of activation obtained with the lexico-semantic task to that obtained with the phonological task was made in order to account for the contribution of lower stage components to semantic processing. No difference in activation was found in Broca's area and superior temporal areas which suggests that these areas are activated by the phonological component of both tasks, but activation was noted in the temporal, parietal and frontal multi-modal association areas. These constitute parts of a large network that represent the specific anatomic substrate of the lexico-semantic processing of language.

Adult↗

The cortical localization of the lexicons. Positron emission tomography evidence.

Positron emission tomography was used to investigate changes in regional cerebral blood flow (rCBF) in neurologically normal subjects during word reading and word repetition. The blood flow in these conditions was compared with control conditions where subjects were presented with stimuli of comparable auditory and visual complexity to real words and said the same word on presentation of each stimulus. The control condition for word repetition (hearing spoken words presented backwards) resulted in bilateral activation of the superior temporal gyrus. Word repetition caused a significant increase in rCBF over this control condition in the left superior and middle temporal gyri. The control condition for word reading (seeing stimuli written in 'false fonts', i.e. non-existent letter-like forms) resulted in significant changes in rCBF bilaterally in the striate and extrastriate cortex. Word reading caused a significant increase in blood flow relative to this control in the posterior part of the left middle temporal gyrus. The implications of these results are discussed, and it is argued that they are consistent with localization of a lexicon for spoken word recognition in the middle part of the left superior and middle temporal gyri, and a lexicon for written word recognition in the posterior part of the left middle temporal gyrus.

Adult↗

Distribution of cortical neural networks involved in word comprehension and word retrieval.

Six normal volunteers were studied with positron emission tomography to identify the cortical neural networks that participate in the processing of single words. Activity-related changes in regional cerebral blood flow were measured consecutively on 6 occasions in each subject, 2 while the subject was at rest and 4 while single word language tasks were being performed. The data from each subject were standardized for brain shape and size, reconstructed parallel to the intercommissural line, normalized for global flow differences, and then averaged for each activation condition across the 6 subjects. Significant areas of change in rCBF (P less than 0.05, with appropriate Bonferroni corrections) between task and rest conditions were displayed with reference to the coordinates of a standard neuroanatomical atlas. We have demonstrated that categorical judgements on heard pairs of real words activate neural networks along both superior temporal gyri, but with an anatomical distribution no different from that seen when the subjects listened to nonwords: the tasks would appear to be very different in cognitive demands but not in terms of the distribution of activation. However, during a verb generation task that involved thinking of verbs appropriate to heard nouns presented at a slow rate, the only temporal region activated was the left posterior superior temporal association cortex (Wernicke's area). Further analysis showed that whereas activation in other superior temporal regions, both left and right, correlated with rates of word presentation during the 4 tasks, there was no such correlation in Wernicke's area; evidence that this site is responsible for more than early acoustic processing. During verb generation there was also activation of left premotor and prefrontal cortex (including Broca's area and the supplementary motor area). The supplementary motor area is thought to be involved in the motor planning of speech. The subjects did not vocalize during the task, and therefore it would appear that the act of retrieving words from semantic memory activates networks concerned with the production of speech sounds. We conclude that single word comprehension and retrieval activate very different distributed regions of cerebral cortex, with Wernicke's area the only region engaged by both processes and with participation during silent word generation of networks involved in vocalization.

Adult↗