Richard Wise

EVALUATION OF CEREBRAL PERFUSION RESERVE IN PATIENTS WITH CAROTID-ARTERY OCCLUSION

Regional cerebral blood flow, oxygen utilisation, fractional oxygen extraction, and cerebral blood volume were measured by positron emission tomography in thirty-two patients with internal-carotid-artery occlusion. In most cases, any reduction in cerebral blood flow in the territory distal to an occluded carotid artery was matched to diminished cerebral metabolic demands. Cerebral blood flow was inappropriately low in only six patients, in whom regional oxygen utilisation was maintained by a compensatory rise in oxygen extraction ratio. The frequent finding of high cerebral blood volume distal to occluded vessels was consistent with a state of focal vasodilatation in response to diminished cerebral perfusion pressure. Analysis of the relation between cerebral blood flow, blood volume, and oxygen extraction ratio suggested that the reduction in cerebral perfusion pressure, and hence circulatory reserve, could be most reliably predicted by the ratio of cerebral blood flow to blood volume. By identifying those patients with carotid occlusion who are most compromised on haemodynamic grounds, combined measurement of cerebral blood flow and blood volume should be valuable in selection of candidates for extracranial-intracranial bypass surgery.

Mechanisms of recovery from aphasia: evidence from positron emission tomography studies

OBJECTIVES Language functions comprise a distributed neural system, largely lateralised to the left cerebral hemisphere. Late recovery from aphasia after a focal lesion, other than by behavioural strategies, has been attributed to one of two changes at a systems level: a laterality shift, with mirror region cortex in the contralateral cortex assuming the function(s) of the damaged region; or a partial lesion effect, with recovery of perilesional tissue to support impaired language functions. Functional neuroimaging with PET allows direct observations of brain functions at systems level. This study used PET to compare regional brain activations in response to a word retrieval task in normal subjects and in aphasic patients who had shown at least some recovery and were able to attempt the task. Emphasis has been placed on single subject analysis of the results as there is no reason to assume that the mechanisms of recovery are necessarily uniform among aphasic patients. METHODS Six right handed aphasic patients, each with a left cerebral hemispheric lesion (five strokes and one glioma), were studied. Criteria for inclusion were symptomatic or formal test evidence of at least some recovery and an ability to attempt word retrieval in response to heard word cues. Each patient underwent 12 PET scans using oxygen-15 labelled water (H2 15O) as tracer to index regional cerebral blood flow (rCBF). The task, repeated six times, required the patient to think of verbs appropriate to different lists of heard noun cues. The six scans obtained during word retrieval were contrasted with six made while the subject was “at rest”. The patients’ individual results were compared with those of nine right handed normal volunteers undergoing the same activation study. The data were analysed using statistical parametric mapping (SPM96, Wellcome Department of Cognitive Neurology, London, UK). RESULTS Perception of the noun cues would be expected to result in bilateral dorsolateral temporal cortical activations, but as the rate of presentation was only four per minute the auditory perceptual activations were not evident in all people. Anterior cingulate, medial premotor (supplementary speech area) and dorsolateral frontal activations were evident in all normal subjects and patients. There were limited right dorsolateral frontal activations in three of the six patients, but a similar pattern was also found in four of the nine normal subjects. In the left inferolateral temporal cortex, activation was found for the normal subjects and five of the six patients, including two of the three subjects with lesions involving the left temporal lobe. The only patient who showed subthreshold activation in the left inferolateral temporal activation had a very high error rate when performing the verb retrieval task. CONCLUSIONS The normal subjects showed a left lateralised inferolateral temporal activation, reflecting retrieval of words appropriate in meaning to the cue from the semantic system. Lateralisation of frontal activations to the left was only relative, with right prefrontal involvement in half of the normal subjects. Frontal activations are associated with parallel psychological processes involved in word retrieval, including task initiation, short term (working) memory for the cue and responses, and prearticulatory processes (even though no overt articulation was required). There was little evidence of a laterality shift of word retrieval functions to the right temporal lobe after a left hemispheric lesion. In particular, left inferolateral temporal activation was seen in all patients except one, and he proved to be very inefficient at the task. The results provide indirect evidence that even limited salvage of peri-infarct tissue with acute stroke treatments will have an important impact on the rehabilitation of cognitive functions.

Generating 'Tiger' as an Animal Name or a Word Beginning with T: Differences in Brain Activation

Positron emission tomography was used to investigate differences in regional cerebral activity during word retrieval in response to different prompts. The contrast of semantic category fluency and initial letter fluency resulted in selective activation of left temporal regions; the reverse contrast yielded activation in left frontal regions (BA44/6). A further comparison between types of category fluency demonstrated a more anterior temporal response for natural kinds and more posterior activation for manipulable manmade objects. These results support behavioural data suggesting that category fluency is relatively more dependent on temporal-lobe regions, and initial letter fluency on frontal structures; and that categorical word retrieval is not a uniformly distributed function within the brain. This is compatible with the category-specific deficits observed after some focal lesions.

Breathlessness in humans activates insular cortex.

Dyspnea (shortness of breath, breathlessness) is a major and disabling symptom of heart and lung disease. The representation of dyspnea in the cerebral cortex is unknown. In the first study designed to explore the central neural structures underlying perception of dyspnea, we evoked the perception of severe ‘air hunger’ in healthy subjects by restraining ventilation below spontaneous levels while holding arterial oxygen and carbon dioxide levels constant. PET revealed that air hunger activated the insular cortex. The insula is a limbic structure also activated by visceral stimuli, temperature, taste, nausea and pain. Like dyspnea, such perceptions underlie behaviors essential to homeostasis and survival.

Functional integration across brain regions improves speech perception under adverse listening conditions

Speech perception is supported by both acoustic signal decomposition and semantic context. This study, using event-related functional magnetic resonance imaging, investigated the neural basis of this interaction with two speech manipulations, one acoustic (spectral degradation) and the other cognitive (semantic predictability). High compared with low predictability resulted in the greatest improvement in comprehension at an intermediate level of degradation, and this was associated with increased activity in the left angular gyrus, the medial and left lateral prefrontal cortices, and the posterior cingulate gyrus. Functional connectivity between these regions was also increased, particularly with respect to the left angular gyrus. In contrast, activity in both superior temporal sulci and the left inferior frontal gyrus correlated with the amount of spectral detail in the speech signal, regardless of predictability. These results demonstrate that increasing functional connectivity between high-order cortical areas, remote from the auditory cortex, facilitates speech comprehension when the clarity of speech is reduced.

The functional neuroanatomy of prelexical processing in speech perception

In this paper we attempt to relate the prelexical processing of speech, with particular emphasis on functional neuroimaging studies, to the study of auditory perceptual systems by disciplines in the speech and hearing sciences. The elaboration of the sound-to-meaning pathways in the human brain enables their integration into models of the human language system and the definition of potential auditory processing differences between the two cerebral hemispheres. Further, it facilitates comparison with recent developments in the study of the anatomy of non-human primate auditory cortex, which has very precisely revealed architectonically distinct regions, connectivity, and functional specialization.

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 (Wernickes 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 Wernickes 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--Wernickes area. Wernickes 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.

Converging Language Streams in the Human Temporal Lobe

There is general agreement that, after initial processing in unimodal sensory cortex, the processing pathways for spoken and written language converge to access verbal meaning. However, the existing literature provides conflicting accounts of the cortical location of this convergence. Most aphasic stroke studies localize verbal comprehension to posterior temporal and inferior parietal cortex (Wernicke’s area), whereas evidence from focal cortical neurodegenerative syndromes instead implicates anterior temporal cortex. Previous functional imaging studies in normal subjects have failed to reconcile these opposing positions. Using a functional imaging paradigm in normal subjects that used spoken and written narratives and multiple baselines, we demonstrated common activation during implicit comprehension of spoken and written language in inferior and lateral regions of the left anterior temporal cortex and at the junction of temporal, occipital, and parietal cortex. These results indicate that verbal comprehension uses unimodal processing streams that converge in both anterior and posterior heteromodal cortical regions in the left temporal lobe.

Evolution of microglial activation in patients after ischemic stroke: A [11C](R)-PK11195 PET study

We obtained [11C](R)-PK11195 PET scans in six patients at different time points between 3 and 150 days after onset of ischemic stroke in order to measure the time course of microglial activation. Increased [11C](R)-PK11195 binding around the lesion was observed as early as 3 days. Scans at later time points showed ongoing changes in the distribution of the [11C](R)-PK11195 signal, involving the area of the primary lesion and areas distant from the primary lesion site. Our data suggest that [11C](R)-PK11195 PET can be used to investigate both the primary lesion and remote pathological changes following Wallerian degeneration.

A comparison of visceral and somatic pain processing in the human brainstem using functional magnetic resonance imaging

Evidence from both human and animal studies has demonstrated a key role for brainstem centers in the control of ascending nociceptive input. Nuclei such as the rostral ventromedial medulla and periaqueductal gray (PAG) are able to both inhibit and facilitate the nociceptive response. It has been proposed that altered descending modulation may underlie many of the chronic pain syndromes (both somatic and visceral). We used functional magnetic resonance imaging to image the neural correlates of visceral and somatic pain within the brainstem. Ten healthy subjects were scanned twice at 3 tesla, during which they received matched, moderately painful, electrical stimuli to either the midline lower abdomen or rectum. Significant activation was observed in regions consistent with the PAG, nucleus cuneiformis (NCF), ventral tegmental area/substantia nigra, parabrachial nuclei/nucleus ceruleus, and red nucleus bilaterally to both stimuli. Marked spatial similarities in activation were observed for visceral and somatic pain, although significantly greater activation of the NCF (left NCF, p = 0.02; right NCF, p = 0.01; Students paired t test, two-tailed) was observed in the visceral pain group compared with the somatic group. Right PAG activity correlated with anxiety during visceral stimulation (r = 0.74; p < 0.05, Pearsons r, two-tailed) but not somatic stimulation. We propose that the differences in NCF and right PAG activation observed may represent a greater nocifensive response and greater emotive salience of visceral over somatic pain.