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Biomedical subjects

Christopher J Mathias

Publications and source records attributed to Christopher J Mathias.

27 records · Page 2Linked to original sources
PubMed2003

Changes in cerebral morphology consequent to peripheral autonomic denervation.

Pure autonomic failure (PAF) is characterized by an acquired, selective, peripheral denervation of the autonomic nervous system. Patients with PAF fail to generate bodily states of arousal via the autonomic nervous system in response to physical or cognitive effort. We used voxel-based morphometry to test the hypothesis that changes in the morphology of brain regions involved in autonomic control would arise as a consequence to the longstanding absence of peripheral autonomic responses in PAF patients. Optimized voxel-based morphometry of structural magnetic resonance scans was used to test for regional differences in grey and white matter in 15 PAF patients and matched controls. There were no group differences observed in global measures of grey matter, white matter, or cerebrospinal fluid (CSF). We identified morphometric differences reflecting regional decreases in grey matter volume and concentration in anterior cingulate and insular cortices in PAF patients relative to controls. Morphometric differences in brainstem and subcortical regions did not reach statistical significance. Our findings suggest that peripheral autonomic denervation is associated with grey matter loss in cortical regions encompassing areas that we have previously shown are functionally involved in generation and representation of bodily states of autonomic arousal. The nature of these changes cannot be determined from morphometric analysis alone, but we suggest that they reflect experience-dependent change consequent upon loss of afferent input to brain regions involved in representation of autonomic states.

Adult↗
PubMed2002

Fear conditioning in humans: the influence of awareness and autonomic arousal on functional neuroanatomy.

The degree to which perceptual awareness of threat stimuli and bodily states of arousal modulates neural activity associated with fear conditioning is unknown. We used functional magnetic neuroimaging (fMRI) to study healthy subjects and patients with peripheral autonomic denervation to examine how the expression of conditioning-related activity is modulated by stimulus awareness and autonomic arousal. In controls, enhanced amygdala activity was evident during conditioning to both "seen" (unmasked) and "unseen" (backward masked) stimuli, whereas insula activity was modulated by perceptual awareness of a threat stimulus. Absent peripheral autonomic arousal, in patients with autonomic denervation, was associated with decreased conditioning-related activity in insula and amygdala. The findings indicate that the expression of conditioning-related neural activity is modulated by both awareness and representations of bodily states of autonomic arousal.

Aged↗
PubMed2002

Volitional control of autonomic arousal: a functional magnetic resonance study.

Electrodermal activity reflects autonomic sympathetic innervation of dermal sweat glands providing an index of emotion-related bodily states of arousal. Relaxation techniques, which are facilitated by external (bio)feedback of electrodermal activity, can be used by trained subjects to actively control bodily and emotional arousal. Biofeedback relaxation provides an experimental model to explore neural mechanisms contributing to emotional representations and intentional autonomic control. We used functional magnetic resonance imaging (fMRI) to explore neural mechanisms contributing to integration of volitional intent, self-representation, and autonomic states of arousal, embodied within performance of a biofeedback relaxation exercise. Data were obtained from 17 subjects to assess brain activity during relaxation in which a visual index of electrodermal arousal was modulated by accuracy (addition of random "noise") or sensitivity (by scalar adjustments of feedback). A central matrix of cortical, subcortical and brainstem autonomic centres was activated during biofeedback relaxation, as well as regions that mediate visual and somatesthetic representations and executive control. Anterior cingulate, amygdala, and insula activity was modulated by task manipulations that increased demand on processing interoceptive representations, while variation in anterior insula activity reflected an interaction between accuracy and sensitivity of feedback. These findings identify neural substrates that support integration of perceptual processing, interoception, and intentional modulation of bodily states of arousal.

Adult↗
PubMed2002

Postural variation in intraocular pressure in primary chronic autonomic failure.

Patients with syndromes of generalised autonomic failure often have extreme posture-related lability of blood pressure, with both orthostatic hypotension and recumbent hypertension. Whether these changes influence intraocular pressure (IOP) is not known. Mean arterial pressure (MAP) and IOP were measured in response to variations in posture between +45 degrees and -20 degrees in 8 normal subjects and 9 subjects with primary generalised chronic autonomic failure (AF). With postural change normal subjects showed minimal change in MAP (p=0.6) and small but significant changes in IOP (p < 0.001). Subjects with AF showed large and significant changes in both MAP (p < 0.001) and IOP (p < 0.001). Two AF subjects had raised IOP when recumbent, despite normal IOP at +45 degrees. There was significant covariance of MAP and IOP (p < 0.001 overall, p=0.004 in normal subjects, p=0.006 in AF subjects). However, individually, those patients with large changes in IOP could not be predicted from changes in MAP. These data show that patients with autonomic failure are subject to large posture-related changes in IOP. These appear to be related to the large posture-induced changes in systemic blood pressure which occur in these patients.

Aged↗
PubMed2002

Haemodynamic responses during head-up tilt and tilt reversal in two groups with chronic autonomic failure: pure autonomic failure and multiple system atrophy.

Continuous haemodynamic responses to head-up tilt (HUT) and its reversal were studied in 21 subjects with sympathetic denervation due to primary chronic autonomic failure; 10 had pure autonomic failure (PAF; peripheral failure) and 11 had multiple system atrophy (MSA; central failure); 8 healthy subjects (controls) also were studied. Supine systolic, diastolic and mean arterial pressure (MAP) and total peripheral resistance (TPR) were highest in PAF. The MAP response to HUT and tilt reversal were different between groups. After HUT, MAP increased in controls (12+/-4 mmHg), but decreased in PAF and MSA (41+/-4 & 19+/-4 mmHg respectively); the fall in PAF was greater than in MSA. With tilt reversal, MAP returned promptly, but not entirely to pretilt levels in controls, with small (insignificant) overshoots in MSA and PAF. The TPR response to HUT and tilt reversal was different between groups. After HUT, TPR increased in controls (0.31+/-0.04 PRU), decreased in PAF (0.23+/-0.1 PRU) and was unchanged in MSA. With tilt reversal, TPR remained elevated (15 %) above baseline in the controls and rose in PAF (13 %) with no change in MSA. There were no differences in supine heart rate (HR), stroke volume (SV) or cardiac output (CO) between the three groups; HR, SV or CO responses to HUT or tilt reversal also did not differ between the groups. Thus, after HUT, MAP decreased, with greater hypotension induced in PAF than MSA. Since CO did not differ between groups, the decrease in TPR appears to account for the greater fall in BP in PAF than in MSA. The elevated TPR at rest pre-tilt and after tilt reversal probably contributed to supine hypertension in PAF. These haemodynamic observations may aid therapeutic strategies to reduce orthostatic hypotension and prevent supine hypertension.

Aged↗
PubMedDate not supplied

To stand on one's own legs.

A fundamental human expectation is to stand upright. This exposes the cardiovascular system to gravitational forces, with a fall in pressure above heart level exposing organs such as the brain to impaired perfusion if adequate adaptive mechanisms are not activated. The autonomic nervous system plays an important role in the initial response to standing upright, and can be affected by several disorders, some rare, some common. Autonomic failure can result in orthostatic hypotension with hypoperfusion of vital organs, causing a variety of symptoms including syncope. Thus, it is important to recognise orthostatic hypotension, determine its aetiology, evaluate and treat it. Intermittent autonomic dysfunction (such as neurally mediated syncope without chronic neurogenic failure) also results in falls and syncope; various forms include the 'common faint' (vasovagal syncope) and carotid sinus hypersensitivity (especially in the elderly). Orthostatic intolerance without orthostatic hypotension is increasingly recognised as due to an autonomic disturbance. New techniques are helping to unravel the functional anatomy of cerebral autonomic centres and their pathways in the causation of orthostatic intolerance.

Autonomic Nervous System↗