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Christopher M Harris

Publications and source records attributed to Christopher M Harris.

10 recordsLinked to original sources
PubMed2006

The main sequence of saccades optimizes speed-accuracy trade-off.

In primates, it is well known that there is a consistent relationship between the duration, peak velocity and amplitude of saccadic eye movements, known as the 'main sequence'. The reason why such a stereotyped relationship evolved is unknown. We propose that a fundamental constraint on the deployment of foveal vision lies in the motor system that is perturbed by signal-dependent noise (proportional noise) on the motor command. This noise imposes a compromise between the speed and accuracy of an eye movement. We propose that saccade trajectories have evolved to optimize a trade-off between the accuracy and duration of the movement. Taking a semi-analytical approach we use Pontryagin's minimum principle to show that there is an optimal trajectory for a given amplitude and duration; and that there is an optimal duration for a given amplitude. It follows that the peak velocity is also fixed for a given amplitude. These predictions are in good agreement with observed saccade trajectories and the main sequence. Moreover, this model predicts a small saccadic dead-zone in which it is better to stay eccentric of target than make a saccade onto target. We conclude that the main sequence has evolved as a strategy to optimize the trade-off between accuracy and speed.

Animals↗
PubMed2006

Infant saccades are not slow.

Saccadic eye movements are essential for redirecting the fovea at different visual targets. In adults and children saccades are remarkably stereotyped. Peak velocity and duration of saccades are a simple function of saccade amplitude called the 'main sequence'. Saccades that are substantially slower than normal often reflect disease of the brain stem saccade generator but may also be associated with diseases of higher level structures including the cerebral hemispheres and superior colliculus. However, little is known about the speed of saccades in infancy. A single previous study reported that infant saccades may be similar to or slower than those of adults, but few saccades were recorded. The present study re-examined this issue with the technique of measuring optokinetic (OKN) quick phases, which are readily elicited from healthy and sick infants, with a view to using saccade speed as a quantitative neurological measure. We measured the duration and peak velocity of saccades (main sequence) using direct-current electro-oculography from OKN quick phases in 18 infants (nine males, nine females) aged 2 to 18 months (mean age 8 mo [SD 4]) and seven adult comparison participants (four males, three females; age range 21-32 y, mean age 27 y [SD 3]). All infant saccades showed typical relationships between duration, peak velocity, and amplitude. Overall, there was no statistically significant difference between adult and infant main sequences for duration or peak velocity. However, the differences in the main sequence for duration almost reached significance (p=0.051) for infant saccades being faster than adults. Individual differences were also present, and some infants produced saccades faster than adults, but not slower. There was no significant age trend. We conclude that measuring saccade speed is practicable in the young infant. From the age of at least 2 months, infants generate saccades with speeds similar to or slightly higher than those of adults.

Adult↗
PubMed2004

Joubert syndrome: long-term follow-up.

Twenty-nine patients (16 males, 13 females) with Joubert syndrome were identified from ophthalmology, neurology, and genetic databases covering a 15-year period at Great Ormond Street Hospital, London. Criteria for diagnosis included absent or markedly hypoplastic cerebellar vermis, abnormal eye movements, and developmental delay. Five patients had died. Scans and notes were available for 22 patients, and 18 cases were clinically reviewed. The median age was 10 years 10 months (range 3mo to 19y) and the median follow-up was 8 years 5 months (range 3mo to 19y, with one new patient seen at 3mo of age). Cerebellar vermis hypoplasia/aplasia with 'molar tooth sign' in the axial plane was present in 22 of 22 patients, coloboma in 6 of 22, and polydactyly in 6 of 22. In the 18 clinically reviewed, apnoea occurred in 13 patients. Five had renal problems with cysts and 4 of 5 had abnormal electroretinograms (ERGs). Visual electrophysiology was abnormal in 14 of 18 patients, and in 6 there was evidence of deterioration in the ERG. Blood investigations of organic acids, phytanic acid, very-long-chain fatty acid, and transferrin were normal in 12 patients tested. Developmental assessment showed that 6 of 15 patients aged more than 5 years were at mainstream school, and 12 of 18 had started walking between 22 months and 10 years. Speech difficulties and behavioural problems were prominent.

Achilles Tendon↗
PubMed2003

Ocular tilt reaction due to a mesencephalic lesion in juvenile polyarteritis nodosa.

PURPOSE: To describe a case of ocular tilt reaction caused by vasculitic lesions in the midbrain in a child with polyarteritis nodosa. DESIGN: Observational case report. METHODS: A 5-year-old girl with a chronic illness developed diplopia associated with a left head tilt, right hypertropia, torsional nystagmus, slowed vertical saccades and poor convergence. Fundoscopic examination demonstrated conjugate leftward torsion of the eyes consistent with a sustained ocular tilt reaction.Renal angiography confirmed polyarteritis nodosa and cerebral magnetic resonance imaging demonstrated mesencephalic pathology. CONCLUSIONS: Polyarteritis nodosa is a difficult condition to diagnose in a child and can cause brainstem lesions. This rare case of ocular tilt reaction of midbrain origin highlights that a sustained head tilt in a child can be due to brainstem pathology, rather than a fourth nerve palsy.

Aspirin↗
PubMed2002

Modulation of the zinc(II) center in protein farnesyltransferase by mutagenesis of the zinc(II) ligands.

Protein farnesyltransferase (PFTase) is a zinc-containing metalloenzyme that catalyzes the alkylation of cysteine (C) in protein substrates containing a C-terminal "CaaX" motif by farnesyl diphosphate (FPP). In yeast PFTase Zn(II) is coordinated to D307, C309, and H363 in the beta-subunit. The inner coordination sphere of the metal also contains a water molecule to give a net charge of 0 for the tetracoordinate Zn(II) center. When the protein substrate binds, the water molecule is replaced by the thiol of the cysteine residue, and the thiol is deprotonated to generate a Zn(II)-stabilized thiolate in the PFTase.FPP.protein ternary complex for the ensuing prenyl transfer reaction. An expression system was constructed for yeast PFTase containing a His(6) tag at the C-terminus of the beta-subunit to facilitate purification of the wild-type enzyme and site-directed mutants. The amino acids that coordinate Zn(II) were substituted to give a series of mutant PFTases with net charges of +1, 0, -1, and -2 at the Zn(II) center of the ternary enzyme.substrate complexes. Wild-type PFTase and the site-directed mutants were purified as alpha,beta-heterodimers, and each was found to contain an equivalent of Zn(II). All of the mutants were less reactive than wt PFTase (net charge of -1), with the greatest losses of activity seen for the mutants with net charges of 0 and +1. Equilibrium binding experiments with dGCVIA peptide and an unreactive analogue of FPP, (E,E)-2-[2-oxo-2-[[(3,7,11-trimethyl-2,6,10-dodecatrienyl)oxy]amino]ethyl]phosphonate (FNP), established that all of the mutants bound an equivalent of the peptide substrate. Like wt PFTase, the pH dependence of K(D) for the mutants did not change significantly between pH 5 and pH 9, indicating that pK(A)s for the thiol moiety in the (mutant PFTase).FNP.peptide complexes were <5. dGSVIA and dG(beta-NH2-Ala)VIA, where the sulfhydryl moiety was replaced by hydroxyl and amino groups, respectively, were not substrates. These experiments suggest a direct relationship between the net charge of the Zn(II) center in PFTase and the reactivity of the peptide thiolate that is alkylated by FPP.

Alkyl and Aryl Transferases↗
PubMedDate not supplied

Exploring smoothness and discontinuities in human motor behaviour with Fourier analysis.

The popular notion that human movements are smooth appears to be in contradiction to the fact that point-to-point movements must necessarily have discontinuities of some finite order at their onset and possibly offset. We explore discontinuities in the Fourier domain and show that the order and total strength of discontinuities in a trajectory can be measured from the slope and intercept of the envelope of the energy spectrum at high frequencies. In linear system models, the order of discontinuity is constrained by the motor command discontinuity and the order of the motor plant. We deduce that trajectories such as the minimum jerk are not smooth, and may even be the least smooth trajectories possible for biologically plausible motor plants. We further examine the role of discontinuities in optimal control and show that minimum square derivative profiles (such as minimum jerk) are time-optimal trajectories. This leads to the notion that point-to-point movements are a trade-off between duration and discontinuity strength, possibly reflecting neural command intensity or signal-dependent noise.

Fourier Analysis↗
PubMedDate not supplied

Temporal uncertainty in reading the neural code (proportional noise).

It is widely accepted that neural information is encoded in the timing of action potentials. However, such information can only be transmitted if the receiver (soma, muscle fibre) can measure time precisely. We argue that such timing is inevitably imprecise due to biological fluctuations in receiver function. We show that this leads to a receiver output, where the standard deviation of receiver output noise is proportional to the mean level of the receiver output. Proportional noise is fundamentally distinct from the common assumption of square-root relationship seen in renewal processes (e.g. Poisson noise), which is usually assumed in neural firing patterns. We show that proportional noise may be the limiting constraint in receiver function, and that it could account for such diverse perceptual and motor behaviours encompassed by Weber's and Fitt's laws, as well as the dynamic trajectories of rapid feed-forward motor behaviours such as arm reaching and saccades. We conclude that temporal uncertainty should be potentially a fundamental stochastic constraint on network function and behaviour.

Action Potentials↗