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Biomedical subjects

P W Halligan

Publications and source records attributed to P W Halligan.

At least 19 recordsLinked to original sources
PubMed2005

Simulating sensory-motor incongruence in healthy volunteers: implications for a cortical model of pain.

OBJECTIVES: Conflict between motor-sensory central nervous processing has been suggested as one cause of pain in those conditions where a demonstrable or local nociceptive aetiology cannot be convincingly established (e.g. complex regional pain syndrome type 1, repetitive strain injury, phantom limb pain and focal hand dystonia). The purpose of this study was to discover whether pain could be induced in pain-free healthy volunteers when this conflict was generated transiently in a laboratory setting. METHODS: Forty-one consecutively recruited healthy adult volunteers without a history of motor or proprioceptive disorders performed a series of bilateral upper and lower limb movements whilst viewing a mirror/whiteboard, which created varied degrees of sensory-motor conflict during congruent/incongruent limb movements. A qualitative method recorded any changes in sensory experience. RESULTS: Twenty-seven subjects (66%) reported at least one anomalous sensory symptom at some stage in the protocol despite no peripheral nociceptive input. The most frequent symptoms occurred when incongruent movement was performed whilst viewing the reflected limb in the mirror condition, the time of maximum sensory-motor conflict. Symptoms of pain were described as numbness, pins and needles, moderate aching and/or a definite pain. Other sensations included perceived changes in temperature, limb weight, altered body image and disorientation. There were indications that some individuals were more susceptible to symptom generation than others. CONCLUSIONS: Our findings support the hypothesis that motor-sensory conflict can induce pain and sensory disturbances in some normal individuals. We propose that prolonged sensory-motor conflict may induce long-term symptoms in some vulnerable subjects.

Adult↗
PubMed2003

Referred sensations in patients with complex regional pain syndrome type 1.

OBJECTIVES: This study sought to explore and characterize referred sensations (RS) in patients with complex regional pain syndrome (CRPS) type 1 and test the hypothesis that pain in CRPS is associated with central sensory changes. METHODS: Subjects underwent standardized neurological examination involving light touch, pinprick and vibration sense with eyes closed and then with eyes open. The subjects described the location and sensation emanating from the stimulated site and whether they experienced any sensations (similar or different) elsewhere. RESULTS: Five of 16 subjects recruited demonstrated RS. These were experienced in real time, were modality specific (touch and pinprick) and were located on the body part immediately adjacent, on Penfield's cortical homunculus, to the stimulated site. The RS were diminished or absent when the subject visualized the stimulated area. They disappeared when stimulation ceased and on clinical improvement. CONCLUSIONS: This is the first report of RS in CRPS and provides further evidence of central reorganization in what was previously thought to be a peripheral disorder.

Adult↗
PubMed2003

Joint stiffness in a phantom limb: evidence of central nervous system involvement in rheumatoid arthritis.

OBJECTIVE: The nature and cause of perceived joint stiffness (PJS), a well-established and defining symptom of rheumatoid arthritis (RA), remains unclear. We hypothesized that changes in the central nervous system (CNS) may determine and maintain this subjective experience of stiffness in a limb even after it is amputated. To test this hypothesis, patients with a phantom limb (PL) who had experienced characteristic RA stiffness prior to amputation were systematically investigated. METHODS: Three patients with a current diagnosis of RA and lower limb amputation were investigated to determine the nature and pattern of pain and stiffness in their PL and intact limb. In addition to standard physical examination, pain and stiffness severity was measured using visual analogue scales for both limbs. The duration and timing of stiffness were also recorded for each limb. RESULTS: In all three cases, the pattern of perceived RA stiffness was similar for the intact limb and the PL. All three patients described stiffness in their PL which mirrored that of physical RA joint symptoms in terms of quality, frequency, diurnal variation, location, distribution and response to medication [non-steroidal anti-inflammatory drug (NSAID), corticosteroid, opiate and disease-modifying anti-rheumatic drug (DMARD)]. Unilateral exercise (or attempted exercise) relieved stiffness only in the limb being exercised. CONCLUSION: The extent to which the subjective experience of perceived stiffness could be dissociated from the assumed original peripheral source was strikingly illustrated in RA patients with phantom limbs. We suggest that the PJS characteristic of RA is generated and maintained by secondary plastic changes in the CNS, although causally related to the initial peripheral rheumatoid disease process.

Aged↗
PubMed2003

Postoperative hypoxia is a contributory factor to cognitive impairment after cardiac surgery.

OBJECTIVE: Cognitive dysfunction and postoperative hypoxia are common sequelae of coronary artery bypass grafting, but there has been no study to determine whether there is any relationship between them. METHODS: Arterial blood gas measurements were performed before surgical intervention and on the second and fifth postoperative day, and neuropsychological assessments were performed before surgical intervention and 5 days and 3 months postoperatively by using a battery of 10 psychometric tests in 175 patients undergoing coronary artery bypass grafting. An estimate of overall performance on the battery at each assessment point was provided by a simple aggregate cognitive index score calculated from the mean z scores of 4 normally distributed test variables. Multiple regression analysis was performed by using the cognitive index score at day 5 as the dependent variable, with age, sex, duration of the operation, presence or absence of cardiopulmonary bypass, preoperative cognitive index score, and arterial oxygenation and percentage of saturation at day 5 as independent variables. RESULTS: The mean cognitive index score decreased significantly in 115 (66%) patients who agreed to neuropsychological test battery assessment on the fifth postoperative day but improved significantly beyond baseline at 3 months. Mean arterial oxygen tension and percentage of saturation decreased significantly 2 days after the operation and, although improving over the following 3 days, remained decreased at day 5. Decreased cognitive index scores at day 5 strongly predicted cognitive impairment at 3 months (r = 0.36). The only significant independent predictors of the day 5 cognitive index score in the multiple regression analysis were preoperative cognitive index score and arterial oxygenation tension at day 5 (r = 0.24, P <.03). CONCLUSIONS: We report a significant correlation between postoperative cognitive dysfunction and hypoxia 5 days after coronary artery bypass grafting. This finding might have therapeutic implications because early postoperative cognitive dysfunction influences long-term impairment.

Cognition Disorders↗
PubMed2003

A controlled pilot study of the utility of mirror visual feedback in the treatment of complex regional pain syndrome (type 1).

BACKGROUND: We assessed mirror visual feedback (MVF) to test the hypothesis that incongruence between motor output and sensory input produces complex regional pain syndrome (CRPS) (type 1) pain. METHODS: Eight subjects (disease duration > or =3 weeks to < or =3 yr) were studied over 6 weeks with assessments including two controls (no device and viewing a non-reflective surface) and the intervention (MVF). Pain severity and vasomotor changes were recorded. RESULTS: The control stages had no analgesic effect. MVF in early CRPS (< or =8 weeks) had an immediate analgesic effect and in intermediate disease (< or =1 yr) led to a reduction in stiffness. At 6 weeks, normalization of function and thermal differences had occurred (early and intermediate disease). No change was found in chronic CRPS. CONCLUSIONS: In early CRPS (type 1), visual input from a moving, unaffected limb re-establishes the pain-free relationship between sensory feedback and motor execution. Trophic changes and a less plastic neural pathway preclude this in chronic disease.

Adult↗
PubMed2003

Neuroprotection during cardiac surgery: a randomised trial of a platelet activating factor antagonist.

OBJECTIVE: To assess platelet activating factor (PAF) antagonists, potent neuroprotective agents in experimental cerebral dysfunction, in clinical practice. DESIGN: Double blind, minimised, placebo controlled trial of low and high dose PAF antagonist (lexipafant). SETTING: Cardiac surgery unit. PATIENTS: 150 patients undergoing coronary artery bypass graft (CABG) surgery using cardiopulmonary bypass. INTERVENTIONS: Randomisation to placebo, low dose (10 mg) or high dose (100 mg) lexipafant. MAIN OUTCOME MEASURES: Incidence of impairment on four established cognitive tests, undertaken before, five days, and three months after CABG, examined by three methods for defining impairment. RESULTS: The three groups were similar with respect to preoperative and intraoperative factors. Observed levels of cognitive impairment were less than had been predicted from previous studies. There was no difference in the groups in cognitive change scores at five days or three months. Group mean analysis showed significant time factors for all four tests but not for interactions or for the lexipafant group. A composite cognitive index, based on the aggregate of four normally distributed tests, showed a significant effect for timing of the test but not for the lexipafant group or interaction. Age, but not duration of bypass, was the most important determinant of postoperative cognitive impairment. CONCLUSIONS: The neuroprotective PAF antagonist lexipafant did not differentially reduce the level of cognitive impairment after CABG as determined by power estimates derived from published studies. The strongest predictors of cognitive impairment were age and timing of the test after operation.

Cognition Disorders↗
PubMed2001

Switching between the forest and the trees: brain systems involved in local/global changed-level judgments.

Visual targets can be coded, in relative terms, at either the local or the global level of stimuli. Previous studies have indicated that targets are identified more slowly when they appear at a new hierarchical level, compared to when they reappear at the same level as in the previous trial. In the present study, we used measures of reaction time and event-related fMRI to investigate factors affecting this switch cost. In particular, we examined the effects of the number of repeated-level trials preceding a switch and whether the cue to switch was either externally or internally mediated. At the behavioral level we found that (1) the time taken to identify a target on a changed-level trial is longer following four repeated-level trials compared to two repeated-level trials, but that runs of six do not produce additional costs over four, and (2) targets can be identified faster following externally cued switches compared to internally mediated switches. We then show that these behavioral effects are associated with distinct patterns of neural activation. Switches performed after two repeated-level trials preferentially activated the precuneus, while those performed after both four and six activated bilateral inferior parietal cortex and motor hand area. Relative to external switches, internal switches activated the putamen, while both kinds of switch conjointly activated the large-scale network proposed to underlie internal/external switches in nonhierarchical tasks. Our data further clarify the mechanisms mediating hierarchical selection.

Adult↗
PubMed2001

Graphic neglect--more than the sum of the parts.

Patients who seem to "ignore" objects or people on one side of space have been described in the medical literature for well over a century. The term "visuospatial neglect" is now used to describe the cluster of behaviors whereby patients after unilateral cerebral lesions (most frequently of right parietal cortex) fail to attend or explore (predominantly) the side of space contralateral to the lesion. Although the condition comprises a complex disruption of space-related behaviors, the prevailing view was that the different symptoms could be accommodated in terms of damage to one of three different cognitive mechanisms mediating attention (e.g., K. M. Heilman and E. Valenstein, Ann. Neurol. 5: 166-170, 1979), intention (R. T. Watson, E. Valenstein, and K. Heilman, Ann. Neurol. 3: 505-508, 1978), and/or representation (E. Bisiach, Q. J. Exp. Psychol. 46: 435-461, 1993). The general consensus favors an attentional deficit but the notion of attention has always proved conceptually slippery and difficult to operationalize (P. W. Halligan and J. C. Marshall, Cogn. Neuropsychol. 11: 167-206, 1994a). In this paper, we consider how drawing performance after right brain damage in patients with "visual neglect" reveals the involvement and interplay of several cognitive deficits, including aspects of mental representation and spatial awareness.

Agraphia↗
PubMed2001

Is there a relationship between cognitive dysfunction and systemic inflammatory response after cardiopulmonary bypass?

BACKGROUND: The systemic inflammatory reaction (SIR) is assumed to be one of the factors that causes cerebral dysfunction after cardiopulmonary bypass (CPB). The aim of the present study was to evaluate the relationship between the SIR and postoperative cognitive performance at 5 days and 3 months. METHODS: One hundred patients undergoing coronary artery bypass grafting were studied. Inflammatory markers and markers of coagulation and fibrinolysis were determined at several time points during and after the operation. Correlation analysis between maximum levels of the different markers and early and late performance was performed. RESULTS: No overall association was found between the maximum levels of the inflammatory markers and early and late function. CONCLUSIONS: Notwithstanding limitations of statistical power established markers of systemic inflammatory reaction showed no relationship with outcome at 5-day or 3-month follow-up in this subset of patients.

Aged↗
PubMed2001

Cognitive neuropsychiatry: towards a scientific psychopathology.

Cognitive neuropsychiatry represents a systematic and theoretically driven approach to explain clinical psychopathologies in terms of deficits to normal cognitive mechanisms. A concern with the neural substrates of impaired cognitive mechanisms links cognitive neuropsychiatry to the basic neurosciences. The emergence of cognitive neuropsychiatry in the 1990s illustrates the growing rapprochement between cognitive neuropsychology, clinical medicine and the neurosciences in addressing common questions about disorders of the mind/brain. In reviewing recent applications, we highlight how this hybrid discipline will make a distinctive contribution to the science of psychopathology.

Brain↗
PubMed2001

Characterising phantom limb phenomena in upper limb amputees.

A systematic descriptive survey was carried out on a clinic population with acquired upper limb amputation in which clear distinctions were made between phantom experiences, pre-amputation pain and stump pain. It was found that of 76 participants 96% reported phantom experiences and 84% were currently experiencing phantom limb phenomena (PLP). Sixty-nine percent (69%) of those currently experiencing phantom phenomena stated that the phantoms were painful. Significant relationships were found between frequency of phantom experiences and side and level of amputation. In addition, the presence of 'trigger' points reported by a sub group of participants was found to be associated with the frequency of phantoms and painful phantoms. This finding could provide support for cortical reorganisation post amputation. It is suggested that detailed individual 'profiling' of phantom experiences is important and would have the following implications: it would contribute to existing knowledge and provide new insights into the central nervous system's reorganisation post-amputation; it would provide an accurate way of representing amputees' anomalous perceptions; it would alert health professionals to the presence, variety and extent of PLP following amputation.

Adolescent↗
PubMed2000

Line bisection judgments implicate right parietal cortex and cerebellum as assessed by fMRI.

OBJECTIVE: To use functional MRI (fMRI) to determine which brain regions are implicated when normal volunteers judge whether pretransected horizontal lines are correctly bisected (the Landmark test). BACKGROUND: Manual line bisection and a variant thereof involving perceptual judgments of pretransected lines (the Landmark test) are widely used to assess unilateral visuospatial neglect in patients with neurologic disease. Although unilateral (left) neglect most often results from lesions to right temporoparietal cortex, the normal functional anatomy of the Landmark test has not been convincingly demonstrated. METHODS: fMRI was carried out in 12 healthy right-handed male volunteers who judged whether horizontal lines were correctly prebisected. In the control task, subjects detected whether the horizontal lines contained a transection mark irrespective of the position of that mark. Response was by two-choice key press: on half the trials, subjects used the right, and on half, the left hand. Statistical analysis of evoked blood oxygenation level-dependent responses, measured with echoplanar imaging, employed statistical parametric mapping. RESULTS: Performing the Landmark task showed neural activity (p < 0.05, corrected) in the right superior posterior and right inferior parietal lobe, early visual processing areas bilaterally, the cerebellar vermis, and the left cerebellar hemisphere. Only the latter area showed a significant interaction with hand used. CONCLUSIONS: The right hemispheric dominance observed in inferior parietal cortex is consistent with the results of lesion studies. Right superior parietal cortex, vermis, and left cerebellar hemisphere have not been implicated in neglect, but all appear to play a cognitive role in the Landmark task.

Adult↗
PubMed2000

Imaging hypnotic paralysis: implications for conversion hysteria.

In a single case study with positron emission tomography (PET) functional imaging, hypnotic paralysis activated similar brain areas to those in conversion hysteria, supporting the view that hypnosis and hysteria might share common neurophysiological mechanisms.

Adult↗
PubMed2000

Is there a relationship between serum S-100beta protein and neuropsychologic dysfunction after cardiopulmonary bypass?

OBJECTIVES: Over the past decade, the glial protein S-100beta has been used to detect cerebral injury in a number of clinical settings including cardiac surgery. Previous investigations suggest that S-100beta is capable of identifying patients with cerebral dysfunction after cardiopulmonary bypass. Whether detection of elevated levels S-100beta reflects long-term cognitive impairment remains to be shown. The present study evaluated whether perioperative release of S-100beta after coronary artery operations with cardiopulmonary bypass could predict early or late neuropsychologic impairment. METHODS: A total of 100 patients undergoing elective coronary bypass without a previous history of neurologic events were prospectively studied. To exclude noncerebral sources of S-100beta, we did not use cardiotomy suction or retransfusion of shed mediastinal blood. Serial perioperative measurements of S-100beta were performed with the use of a new sensitive immunoluminometric assay up to 8 hours after the operation. Patients underwent cognitive testing on a battery of 11 tests before the operation, before discharge from the hospital, and 3 months later. RESULTS: No significant correlation was found between S-100beta release and neuropsychologic measures either 5 days or 3 months after the operation. CONCLUSION: Despite using a sensitive immunoluminometric assay of S-100beta, we found no evidence to support the suggestion that early release of S-100beta may reflect long-term neurologic injury capable of producing cognitive impairment.

Anesthesia, General↗
PubMed2000

'Where' depends on 'what': a differential functional anatomy for position discrimination in one- versus two-dimensions.

Line bisection is widely used as a clinical test of spatial cognition in patients with left visuospatial neglect after right hemisphere lesion. Surprisingly, many neglect patients who show severe impairment on marking the center of horizontal lines can accurately mark the center of squares. That these patients with left neglect are also typically poor at judging whether lines are correctly prebisected implies that the deficit can be perceptual rather than motoric. These findings suggest a differential neural basis for one- and two-dimensional visual position discrimination that we investigated with functional neuroimaging (fMRI). Normal subjects judged whether, in premarked lines or squares, the mark was placed centrally. Line center judgements differentially activated right parietal cortex, while square center judgements differentially activated the lingual gyrus bilaterally. These distinct neural bases for one- and two-dimensional visuospatial judgements help explain the observed clinical dissociations by showing that as a stimulus becomes a better, more 'object-like' gestalt, the ventral visuoperceptive route assumes more responsibility for assessing position within the object.

Adult↗
PubMed2000

Neural consequences of acting in near versus far space: a physiological basis for clinical dissociations.

We used PET to determine which brain regions are implicated when normal volunteers bisect horizontal lines and point to dots in near (peripersonal) or far (extrapersonal) space. Studies of line bisection in patients with right hemisphere lesions have shown that bisection performance can be severely impaired in either near or far space while remaining within normal limits in the other spatial domain. Likewise, clinical dissociations between pointing to objects in near and far space have been reported. The normal functional anatomy of these dissociations has not been demonstrated convincingly. Regional cerebral blood flow measurements using PET were carried out in 12 healthy right-handed male volunteers who bisected lines or pointed to dots in near or far space, using a laser pen. Subjects performing either task in near space showed neural activity in the left dorsal occipital cortex, left intraparietal cortex, left ventral premotor cortex and left thalamus. In far space, subjects performing either task showed activation of the ventral occipital cortex bilaterally and the right medial temporal cortex. These data provide physiological support for the clinically observed dissociations demonstrating that attending to and acting in near space differentially employs dorsal visuomotor processing areas, whereas attending to and acting in far space differentially draws on ventral visuoperceptual processing areas, even when the motor components of the tasks are identical when performed in the two spaces.

Adult↗