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Biomedical subjects

I M Donaldson

Publications and source records attributed to I M Donaldson.

At least 19 recordsLinked to original sources
PubMed2001

Dysfluency and involuntary movements: a new look at developmental stuttering.

Studies using modern imaging techniques suggest that, in developmental stuttering, there is dysfunction within the cortical and subcortical areas of the motor control system wider than that pertaining to speech motor control alone. If this is the case, one might expect motor deficits extending beyond and unrelated to the production of speech in people who stutter. This study explored this proposal by investigating the presence and characteristics of involuntary movements accompanying stuttering. Sixteen adults with developmental stuttering and 16 controls matched for age and sex were audio-videotaped during 5 minutes of conversational speech and reading a passage of 350 words. Audio-data were examined for dysfluencies. Movements of the face, head and upper body considered involuntary and not part of normal facial expression or gesture and not part of the mechanics of speech were identified and described from muted video-data. Subjects who stuttered had a higher proportion of classic (within-word) dysfluencies accompanied by involuntary movements (IMs) than controls during speech (24.4% vs. 4.5%, p = .054) and reading (28.6% vs. 4.9%, p = .033). There was no difference in proportion of classic dysfluencies accompanied by IMs between speech and reading for either group. IMs were also seen in both groups during fluent speech, with a similar incidence during free speech (3.9% vs. 3.0%, NS) but a greater incidence in the subjects who stuttered during reading (2.4% vs. 0.8%, p = .03). In contrast, there was no difference between the two groups for IMs accompanying normal (between-word) dysfluencies. This suggests that classic and normal dysfluency and their accompanying IMs have different etiologies. The notion that stuttering and IMs are due to altered function in a motor control system wider than that of speech motor control alone is supported by a higher incidence of IMs in people who stutter during both classic dysfluencies and fluent speech.

Adolescent↗
PubMed2000

The functions of the proprioceptors of the eye muscles.

This article sets out to present a fairly comprehensive review of our knowledge about the functions of the receptors that have been found in the extraocular muscles--the six muscles that move each eye of vertebrates in its orbit--of all the animals in which they have been sought, including Man. Since their discovery at the beginning of the 20th century these receptors have, at various times, been credited with important roles in the control of eye movement and the construction of extrapersonal space and have also been denied any function whatsoever. Experiments intended to study the actions of eye muscle receptors and, even more so, opinions (and indeed polemic) derived from these observations have been influenced by the changing fashions and beliefs about the more general question of how limb position and movement is detected by the brain and which signals contribute to those aspects of this that are perceived (kinaesthesis). But the conclusions drawn from studies on the eye have also influenced beliefs about the mechanisms of kinaesthesis and, arguably, this influence has been even larger than that in the converse direction. Experimental evidence accumulated over rather more than a century is set out and discussed. It supports the view that, at the beginning of the 21st century, there are excellent grounds for believing that the receptors in the extraocular muscles are indeed proprioceptors, that is to say that the signals that they send into the brain are used to provide information about the position and movement of the eye in the orbit. It seems that this information is important in the control of eye movements of at least some types, and in the determination by the brain of the direction of gaze and the relationship of the organism to its environment. In addition, signals from these receptors in the eye muscles are seen to be necessary for the development of normal mechanisms of visual analysis in the mammalian visual cortex and for both the development and maintenance of normal visuomotor behaviour. Man is among those vertebrates to whose brains eye muscle proprioceptive signals provide information apparently used in normal sensorimotor functions; these include various aspects of perception, and of the control of eye movement. It is possible that abnormalities of the eye muscle proprioceptors and their signals may play a part in the genesis of some types of human squint (strabismus); conversely studies of patients with squint in the course of their surgical or pharmacological treatment have yielded much interesting evidence about the central actions of the proprioceptive signals from the extraocular muscles. The results of experiments on the eye have played a large part in the historical controversy, now in at least its third century, about the origin of signals that inform the brain about movement of parts of the body. Some of these results, and more of the interpretations of them, now need to be critically re-examined. The re-examination in the light of recent experiments that is presented here does not support many of the conclusions confidently drawn in the past and leads to both new insights and fresh questions about the roles of information from motor signals flowing out of the brain and that from signals from the peripheral receptors flowing into it. There remain many lacunae in our knowledge and filling some of these will, it is contended, be essential to advance our understanding further. It is argued that such understanding of eye muscle proprioception is a necessary part of the understanding of the physiology and pathophysiology of eye movement control and that it is also essential to an account of how organisms, including Man, build and maintain knowledge of their relationship to the external visual world. The eye would seem to provide a uniquely favourable system in which to study the way in which information derived within the brain about motor actions may interact with signals flowing in from peripheral receptors. The review is constructed in relatively independent sections that deal with particular topics. It ends with a fairly brief piece in which the author sets out some personal views about what has been achieved recently and what most immediately needs to be done. It also suggests some lines of study that appear to the author to be important for the future.

Afferent Pathways↗
PubMed2000

Zinc stoichiometry of yeast RNA polymerase II and characterization of mutations in the zinc-binding domain of the largest subunit.

Atomic absorption spectroscopy demonstrated that highly purified RNA polymerase II from the yeast Saccharomyces cerevisiae binds seven zinc ions. This number agrees with the number of potential zinc-binding sites among the 12 different subunits of the enzyme and with our observation that the ninth largest subunit alone is able to bind two zinc ions. The zinc-binding motif in the largest subunit of the enzyme was investigated using mutagenic analysis. Altering any one of the six conserved residues in the zinc-binding motif conferred either a lethal or conditional phenotype, and zinc blot analysis indicated that mutant forms of the domain had a 2-fold reduction in zinc affinity. Mutations in the zinc-binding domain reduced RNA polymerase II activity in cell-free extracts, even though protein blot analysis indicated that the mutant subunit was present in excess of wild-type levels. Purification of one mutant RNA polymerase revealed a subunit profile that was wild-type like with the exception of two subunits not required for core enzyme activity (Rpb4p and Rpb7p), which were missing. Core activity of the mutant enzyme was reduced 20-fold. We conclude that mutations in the zinc-binding domain can reduce core activity without altering the association of any of the subunits required for this activity.

Amino Acid Sequence↗
PubMed2000

Baroreceptor denervation presenting as part of a vagal mononeuropathy.

A 48-year-old woman presented with a history of progressive cough, dysphonia, dysphagia, and postural symptoms. Subsequent neurological investigations were consistent with a bilateral vagal mononeuropathy, and neurosarcoidosis was diagnosed after scalene node biopsy. Autonomic investigations including microneurography, neurohormones, and heart rate variability demonstrated arterial and cardiopulmonary baroreflex failure. In addition, parasympathetic control of heart rate was absent and consistent with a bilateral, nonselective lesion in the proximal vagus.

Arginine Vasopressin↗
PubMed2000

Afferent signals from the extraocular muscles affect the gain of the horizontal vestibulo-ocular reflex in the alert pigeon.

We have shown previously that the gain of the horizontal vestibulo-ocular reflex (HVOR) is modified by afferent signals from extraocular muscle proprioceptors in the decerebrate pigeon. We have now analysed the variability of the HVOR in intact, alert pigeons and, using the artificial vestibulo-ocular reflex method, have found that in all of the pigeons tested afferent signals from the extraocular muscle proprioceptors modify the gain, but not the phase, of the HVOR. While this effect was seen in a given bird only on some occasions, when present it was consistent in magnitude and direction and closely similar to our previous observations on decerebrate pigeons. These results from alert, intact birds strengthen the evidence that extraocular muscle afferent signals play a part in the control of the vestibulo-ocular reflex.

Animals↗
PubMed2000

Real-time detection of epileptiform activity in the EEG: a blinded clinical trial.

The aim of this study was to determine the performance of a PC-based system for real-time detection and topographical mapping of epileptiform activity (EA) in the EEG during routine clinical recordings. The system incorporates a mimetic stage to locate candidate spikes (including sharp-waves) followed by two expert-system-based stages, which utilize spatial and wide-temporal contextual information in deciding whether candidate events are epileptiform or not. The data comprised 521 consecutive routine clinical EEG recordings (173 hours). Performance was evaluated by comparison with three independent electroencephalographers (EEGers-I). A second group of two EEGers (EEGers-II) separately interpreted the spike topographical maps and, for EEGs categorized as containing only questionable EA by the detection system, reviewed 6 sec segments of raw EEG centered on each questionable event. Thirty-eight of the EEGs were considered to contain definite EA by at least two of EEGers-I. The false detection rate of the system was 0.41 per hour. The system was found to have a sensitivity of 76% and a selectivity of 41% for EEGs containing definite EA. However, it only missed detection of EA in 5% of the recordings. EEGers-II agreed with EEGers-I on the distribution (generalized, lateralized, focal, multifocal) of EA in 79% of cases. This is by far the largest clinical evaluation of computerized spike detection reported in the literature and the only one to apply this in routine clinical recordings. The false detection rate is the lowest ever reported, suggesting that this multi-stage rule-based system is a powerful and practical tool in clinical electroencephalography and long-term EEG monitoring.

Adolescent↗
PubMed1998

Signals of eye position and velocity in the first-order afferents from pigeon extraocular muscles.

Responses of first-order afferents from the extraocular muscles of the pigeon were studied by extracellular recording in the ophthalmic part of the trigeminal ganglion of decerebrate, paralysed pigeons. The afferents responded to both the amplitude and velocity of ramp displacements of the intact eye with amplitude sensitivities ranging from 0.9 to 8 impulses/s/deg of eye displacement beyond the response threshold. Once a new stable position had been reached, the afferent signal depended only upon the absolute position of the eye within the orbit. The responses adapted in seconds rather than minutes so these units would not provide a continuous signal of the position of an immobile eye; they are best described as signalling position and velocity in relation to eye movements.

Action Potentials↗
PubMed1997

Changes in dorsal neck muscle activity related to imposed eye movement in the decerebrate pigeon.

Movements of the head and eyes are known to be intimately related. Eye position has also been shown to be closely related to the electromyographic activity of dorsal neck muscles; however, extraocular muscle proprioception has not generally been considered to play a part in the control of such movements. We have previously shown that, in the pigeon, imposed movements of one eye modify the vestibular responses of several dorsal neck muscles in ways that are dependent on stimulus parameters such as the amplitude and velocity of imposed eye movement. The present study examines more closely the interactions between imposed eye movements and different muscle pairs. The three neck muscle pairs studied each responded to afferent signals from the extraocular muscles in discrete and specific ways which appeared to be correlated with their different actions. Complementary effects of imposed eye movements in the horizontal plane were seen for both the complexus and splenius muscle pairs, with imposed eye movements in one direction producing the largest inhibition of the ipsilateral muscle's vestibular response and imposed eye movements in the opposite direction the largest inhibition of the contralateral muscle's vestibular response. During roll tilt oscillation (ear-up/ear-down) in the frontal plane, similar complementary effects of imposed eye movement were seen in the complexus muscle pair, but the splenius muscle pair showed little tuning, with similar inhibition for imposed eye movement directed either upwards or downwards. In contrast to these complementary effects, the biventer cervicis muscle pair showed no vestibular modulation during vestibular stimulation in the horizontal plane and their spontaneous activity was not altered by imposed eye movement. During roll-tilt oscillation (ear-up/ear-down) in the frontal plane imposed eye movement directed vertically upwards increased both muscles' vestibular responses and imposed eye movement directed vertically downwards inhibited both muscles' vestibular responses. Section of the ophthalmic branch of the trigeminal nerve (deafferenting the eye muscles) abolished the effects of imposed eye movement on the neck muscle pairs. In conjunction with further control experiments these results provide compelling evidence that proprioceptive signals from the extraocular muscles reach the neck muscles and provide them with a functionally significant signal. We have previously shown that signals from the extraocular muscles appear to be involved in the control of the vestibulo-ocular reflex. It follows from the experiments reported here that proprioceptive signals from the extraocular muscles are also likely to be involved in the control of gaze.

Animals↗
PubMed1996

A technique for removal of the visuoperceptual component from tracking performance and its application to Parkinson's disease.

Although it is well established that subjects with Parkinson's disease perform poorly on complex sensory-motor tasks, the extent to which this is due to visuoperceptual deficits is unclear. We measured the performance of 16 patients with Parkinson's disease, both on and off drugs, and 16 age and sex matched control subjects on preview and nonpreview tracking tasks and a nonmotor test of dynamic visuoperception. Order effects were controlled for by a randomized cross-over design. Performance on the perceptual task was measured in terms of perceptual resolution and was found impaired in the Parkinsonian group. The contribution of visuoperceptual function to tracking performance was removed using the concept of a visuoperceptual buffer-zone. The mean tracking error remained impaired on all tracking tasks and demonstrated that limitations is visuoperceptual function play only a minor role in the tracking errors in both Parkinsonian and control subjects. It is clear that the technique for determining the visuoperceptual component of performance on complex sensory-motor tasks has considerable scope for application in studies of a variety of brain disorders.

Adult↗
PubMed1995

Superoxide dismutase (glu100-->gly) in a family with inherited motor neuron disease: detection of mutant superoxide dismutase activity and the presence of heterodimers.

Superoxide dismutase glu100-->gly, a mutation known to be associated with familial motor neuron disease (familial amyotrophic lateral sclerosis) has been detected in one symptomatic and five of seven asymptomatic members of a family with a history of this disease. On average, the individuals with the mutation had 75% of normal red blood cell superoxide dismutase activity. Native polyacrylamide gels stained for superoxide dismutase activity showed two abnormal bands in the family members identified as carrying the mutation. This indicates that active mutant enzyme is present in red cells and forms stable homodimers and heterodimers with the normal chain. A silent mutation in exon 4, not associated with motor neuron disease, was also detected in one family member.

Amyotrophic Lateral Sclerosis↗
PubMed1995

Fractionation of visuoperceptual dysfunction in Parkinson's disease.

There is considerable evidence that visuoperceptual function is impaired in Parkinson's disease although this view remains contentious. The issue is confounded by studies which have demonstrated impairment of visual sensation, in particular high-contrast visual acuity, in Parkinson's disease. We have measured the visuoperceptual performance of 16 patients with mild to moderate Parkinson's disease, both on and off drugs, and 16 age and sex matched control subjects on non-motor tests of visual resolution, static perception, and dynamic perception. Performance on the perceptual tasks was measured in terms of perceptual resolutions and was found impaired in the parkinsonian group. After removal of the contribution of poorer visual resolution, the overall visual perception remained impaired, although to a relatively subtle degree, such that the difference between the two groups on its static and dynamic components did not reach significance.

Adult↗
PubMed1995

The primary afferent pathway of extraocular muscle proprioception in the pigeon.

Recent physiological experiments in our laboratory suggest that extraocular muscle proprioceptive signals are involved in oculomotor control in the pigeon [e.g., Knox and Donaldson (1993) Proc. R. Soc. Lond. B 253, 77-82]; the present results provide information about the primary afferent pathway involved in these actions. In other physiological experiments [Hayman et al. (1993) Proc. R. Soc. Lond. B 254, 115-122] we have shown that extraocular muscle afferent signals modify vestibularly driven neck reflexes in the pigeon; the present results suggest an anatomical substrate for these effects. The localization of the cell bodies and of the central terminations of afferent fibres from the extraocular muscles of the pigeon was examined using transport of horseradish peroxidase. The results showed that primary afferent cell somata subserving extraocular muscle proprioception are located within the ipsilateral trigeminal ganglion. The presence of heavily labelled brainstem neurons reported in a previous study [Eden et al. (1982) Brain Res. 237, 15-21] was confirmed; however, these cells were shown to be accessory abducens motoneurons innervating the quadratus muscle, and presumably the pyramidalis muscle also, and not proprioceptive afferent somata as had been suggested. The central projections of extraocular muscle afferent neurons were found consistently in a restricted area of the external cuneate nucleus. This is in contrast to findings in a number of mammals in which the terminal label has been seen to cluster in portions of the spinal trigeminal nucleus. The presence of a lateral trigeminal tract in the pigeon, through which the afferent axons course, which terminates exclusively in the ventral portion of the external cuneate nucleus may explain this finding.

Afferent Pathways↗
PubMed1995

Effects of selegiline (deprenyl) on cognition in early Parkinson's disease.

The influence of selegiline (5 mg b.i.d.) on cognition of 20 levodopanaive patients with early Parkinson's disease (PD) was examined in an 8-week, randomized, placebo-controlled, double-blind trial. Clinical evaluations and cognitive tests were administered at baseline and at 8 weeks; patients with PD who received placebo were also examined 8 weeks after subsequent selegiline treatment. By comparison with non-PD controls, patients with PD were impaired on the Wisconsin card sorting task and on the advanced progressive matrices test, but not in terms of their performance on the Rivermead behavioral memory test or on the rod (spatial) orientation test. Selegiline improved scores on the mentation/mood part and the activities of daily living part of the Unified Parkinson's Disease Rating Scale, but it did not improve motor scores on this test, nor did it have clear effects on the specific neuropsychological measures that were examined.

Aged↗
PubMed1993

Afferent signals from pigeon extraocular muscles modify the activity of neck muscles during the vestibulocollic reflex.

Movements of the head and eye which, together, result in changes in the direction of gaze are linked in a number of species, including man, and eye position is known to affect the activity of neck muscles. This head-eye linkage has generally been ascribed to modification of neck muscle activity by internal estimates of eye position derived from motor commands. We have recently shown that afferent signals from stretch receptors in the extraocular muscles are involved in the moment-to-moment control of eye movements during the vestibuloocular reflex (VOR). We have now studied the interactions between head and eye movements by recording the electromyographic activity of several neck muscles during horizontal (yaw) or frontal (roll tilt) vestibular stimulation. Such a stimulus evokes a VOR in the eyes and a vestibulocollic reflex (VCR) in neck muscles. Imposing movements on one eye at saccadic velocities produced considerable inhibition of the VCR response of a number of neck muscles. The magnitude of these effects was dependent on the parameters of the imposed eye movement. Thus systematic changes were seen when the amplitude, velocity or direction of eye movement was varied. Movement of the eye in the opposite direction to that produced by a normal VOR produced a large inhibition of the VCR response, whereas movements in the same direction as the VOR produced only modest inhibition of the VCR response of the neck muscles tested. Slow, sinusoidal, imposed eye movements that mimicked the slow phase of the VOR produced changes in the gain of the VCR response which appear to correct for errors in the imposed eye velocity and thus tend to maintain the direction of gaze. The results show that changes in eye position have striking effects on the electromyographic activity of neck muscles during the VCR, and strongly suggest that extraocular muscle afferent signals are involved in head-eye coordination.

Afferent Pathways↗
PubMed1993

Afferent signals from the extraocular muscles of the pigeon modify the vestibulo-ocular reflex.

Although the extraocular muscles (EOM) contain stretch receptors it is generally thought that the afferent signals which they provide play no role in the control of eye movement. We have previously shown that these afferent signals do modify both the vestibular responses of single units in the oculomotor control system and the electromyographic responses of the EOM during the vestibulo-ocular reflex (VOR). We have now investigated the effect of EOM afferent signals on the VOR itself, by recording the electro-oculogram of one eye while imposing movements on the other eye during the VOR. Moving the eye in a manner which mimics the slow phase of the VOR, we have found that, as the peak velocity of the imposed eye movement increases, the amplitude of eye movement of the other eye decreases. These results confirm that the output of the VOR itself, expressed as movement of the globe, and not merely some of its component parts, is modified by EOM afferent signals.

Afferent Pathways↗