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Biomedical subjects

C Kennard

Publications and source records attributed to C Kennard.

At least 19 recordsLinked to original sources

Identification of an oculomotor biomarker of preclinical Huntington disease.

The authors examined oculomotor function to identify a biomarker of disease progression in genetically confirmed preclinical and early clinical Huntington disease (HD). Initiation deficits of voluntary-guided, but not reflexive, saccades were characteristic of preclinical HD. Saccadic slowing and delayed reflexive saccades were demonstrated in clinical but not preclinical HD. Saccadic measures provide biomarkers of disease progression in both preclinical and early clinical stages of HD.

Adult↗

Cognitive processes in saccade generation.

The analysis of saccades offers an opportunity to study a number of different cognitive processes, such as visuospatial attention, working memory, and volitional conflict. A study of saccades in patients with visuospatial hemineglect, who performed a visual search task, showed repeated fixations on targets previously discovered, yet they often failed to retain the information that a particular target had previously been discovered. High-resolution structural brain scanning showed that this abnormality was due either to a lesion in the right intraparietal sulcus or the right inferior frontal lobe. Detailed analysis of the scanpaths suggested that the former location was associated with an accumulating impairment in remapping target locations across saccades or impaired memory of previously inspected target locations, whereas the latter location was more consistent with a failure to inhibit responses to rightward locations. When combined with a spatial bias to the right, such deficits might explain why many neglect patients often reexamine rightward targets, at the expense of items to their left. The functions of the supplementary eye field (SEF), in the medial frontal lobe, in relation to saccade generation are controversial. A series of studies in a patient with a focal lesion of the right SEF has indicated an important role for the SEF in the rapid self-control of saccadic eye movements and in set-switching (i.e., implementing control in situations of response conflict when ongoing saccadic plans have to be changed rapidly), rather than monitoring errors. In a recent fMRI study of normal subjects, it was shown that the SEF is involved in implementing the resolution of any volitional conflict, whereas other presupplementary motor areas are involved in the generation of volitional plans and processing volitional conflict.

Brain Mapping↗

Saccadic visual search training: a treatment for patients with homonymous hemianopia.

OBJECTIVES: We describe a novel rehabilitation tool for patients with homonymous hemianopia based on a visual search (VS) paradigm that is portable, inexpensive, and easy to deploy. We hypothesised that by training patients to improve the efficiency of eye movements made in their blind field their disability would be alleviated. METHODS: Twenty nine patients with homonymous visual field defects (HVFD) without neglect practised VS paradigms in 20 daily sessions over one month. Search fields comprising randomly positioned target and distracter elements, differing by a single feature, were displayed for three seconds on a dedicated television monitor in the patients' homes. Improvements were assessed by examining response time (RT), error rates in VS, perimetric visual fields (VFs) and visual search fields (VSFs), before and after treatment. Functional improvements were measured using objective visual tasks which represented activities of daily living (ADL) and a subjective questionnaire. RESULTS: As a group the patients had significantly shorter mean RT in VS after training (p<0.001) and demonstrated a variety of mechanisms to account for this. Improvements were confined to the training period and maintained at follow up. Three patients had significantly longer RT after training. They had high initial error rates which improved with training. Patients performed ADL tasks significantly faster after training and reported significant subjective improvements. There was no concomitant enlargement of the VF, but there was a small but significant enlargement of the VSF. CONCLUSION: Patients can improve VS with practice. This usually involves shorter RTs, but occasionally a longer RT in a complex speed-accuracy trade-off. These changes translate to improved overall visual function, assessed objectively and subjectively, suggesting that they represent robust training effects. The underlying mechanism may involve the adoption of compensatory eye movement strategies.

Activities of Daily Living↗

Abnormal gaze strategies during problem solving in Parkinson's disease.

We have taken a novel approach to the study of problem solving involving the detailed analysis of natural scanning eye movements during the 'one touch' Tower of London task. Control subjects and patients with idiopathic Parkinson's disease (PDs) viewed a series of pictures depicting two arrangements of coloured balls in pockets within the upper and lower halves of a computer display. The task was to plan (but not execute) the shortest movement sequence required to rearrange the balls in one half of the display (the Workspace) to match the arrangement in the opposite half (the Goalspace) and indicate the number of moves required for problem solution. As problem complexity increased, control subjects spent proportionally more time fixating the Workspace region. This pattern was found regardless of whether subjects were instructed to solve problems by rearranging balls in the lower or upper visual fields. The distribution of gaze within the Workspace was also found to be problem dependent, with gaze being selectively directed towards the problem critical balls. In contrast, PDs were found to make more errors in the task and failed to show any dissociation in the amount of time fixating the two halves of the display. This pattern suggests that the patients had difficulty in encoding and/or maintaining current goals during problem solving, consistent with a role for fronto-striatal circuits in mechanisms of working memory and attention.

Aged↗

Saccadic distractibility in first-episode schizophrenia.

In the antisaccade paradigm, subjects are instructed to fixate a central point, and then move their eyes towards a position in space in the opposite direction but equidistant to a peripheral, sudden onset target. Antisaccade errors occur when subjects are "distracted" by the target and make a saccade towards it. These errors are more common in patients with schizophrenia but the underlying cause remains unclear. To determine whether antisaccade errors simply reflect a general inability to maintain fixation or are the consequence of a more specific deficit in the strategic control of internally generated actions, patients with first-episode schizophrenia and healthy controls performed three saccadic paradigms which shared the core feature of requiring a prepotent saccade to be suppressed, but varied in their concurrent cognitive demands. We found that both groups showed an increase in errors as the cognitive demands increased across task. However, this increase was significantly steeper in the schizophrenic patients than in the controls. We also found that schizophrenic patients were as able as controls to inhibit prepotent saccades towards a target in a paradigm with no other cognitive demands. Possible explanations of these results include reduced working memory resources and impaired motor preparation in schizophrenia.

Adult↗

Orbitofrontal cortex mediates inhibition of return.

Recent accounts have proposed that orbitofrontal cerebral cortex mediates the control of behavior based on emotional feedback and its somatic correlates. Here, we describe the performance of a patient with circumscribed damage to orbitofrontal cortex during a task that requires switching between sensory-motor mappings, contingent on the occurrence of positive and negative reward feedbacks. In this test, normal subjects and other patients with prefrontal damage show an increase in latencies for eye movements towards locations at which a negative feedback was presented on the preceding trial. In contrast, our patient does not show this reward-dependent inhibition of return effect on saccades. She was also found to make an increased rate of ocular refixations during visual search and used a disorganized search strategy in a token foraging task. These findings suggest that orbital regions of the prefrontal cortex mediate an inhibitory effect on actions directed towards locations that have been subject to negative reinforcement. Further, this mechanism seems to play a role in controlling natural search and foraging behavior.

Adult↗

Ocular flutter associated with a localized lesion in the paramedian pontine reticular formation.

Ocular flutter is a rare horizontal eye movement disorder characterized by rapid saccadic oscillations. It has been hypothesized that it is caused by loss of "pause" neuronal inhibition of "burst" neuron function in the paramedian pontine reticular formation (PPRF); however, there have been no imaging studies confirming such anatomical localization. We report the case of a woman with an acute attack of multiple sclerosis associated both with ocular flutter and a circumscribed pontine lesion, mainly involving the PPRF on magnetic resonance imaging. As she recovered from the attack, both the midline pontine lesion and the ocular flutter dramatically improved. This case is the first clear evidence that at least some cases of ocular flutter are due to lesions involving the PPRF.

Adult↗

Short and long term effects of antipsychotic medication on smooth pursuit eye tracking in schizophrenia.

RATIONALE: Smooth pursuit abnormalities have been observed in antipsychotic naive first-episode patients, suggesting that they are intrinsic to the illness. However, it is not clear whether these abnormalities are as severe as those observed in more chronic patients. In addition, although research suggests that there are no short-term effects of conventional antipsychotic medication, the effects of long-term antipsychotic medication on smooth pursuit eye movements are relatively unknown. OBJECTIVES: To determine the short and long term effects of antipsychotic medication on the smooth pursuit performance of first-episode and chronic patients with schizophrenia. METHODS: We compared the smooth pursuit performance of antipsychotic-treated and untreated first-episode and chronic schizophrenic patients with healthy controls using a comprehensive range of performance measures. This included velocity gain, the number, type and size of intrusive and corrective saccades, and the average time between the change in direction of the target and the change in direction of the eye movement, a measure of subjects' ability to predict target movement. RESULTS: Chronic schizophrenic patients had significantly reduced velocity gain, took longer to respond to the change in target direction and made more catch-up saccades than both first-episode schizophrenic patients and controls. First-episode patients were impaired relative to controls only on the measure of velocity gain. There were no differences between antipsychotic-naive and treated first-episode patients. Antipsychotic-free chronic patients were significantly less impaired on velocity gain than matched continuously treated chronic patients. These results were not influenced by group differences in age and symptom severity. CONCLUSIONS: These results show that: 1) the main index of smooth pursuit, velocity gain, is impaired early in the course of schizophrenia; 2) whereas velocity gain is unaffected by short-term (weeks) medication, it is worsened by chronic (years) treatment; 3) other indices of smooth pursuit, catch-up saccades and ability to predict target movement, are adversely influenced by illness chronicity rather than medication.

Adult↗

The preparation and execution of saccadic eye and goal-directed hand movements in patients with Parkinson's disease.

The oculomotor and manual motor systems were studied in a two-segment movement task in a group of patients with Parkinson's disease and in age matched normal controls. In order to avoid reflexive motor movements the selection of the correct motor sequence was derived from the interpretation of symbolic (coloured) cues. The latencies and dynamics of eye and hand (pointing) movements performed during the first (fixed) movement segment were measured and the planning and execution processes were manipulated by varying the complexity of the second movement segment relative to the first (with regard to direction and amplitude). The results showed that the eye and hand movements made by patients with Parkinson's disease were not impaired in the initiation of the first movement segment. Interestingly, both Parkinson's patients and controls showed increased eye and hand reaction time latencies for the first movement when the second movement was in the direction opposite to the first. This indicates that the complexity of the second movement influences the execution of the first movement, and importantly that complexity affects motor initiation and execution processes in both normal subjects and in patients with Parkinson's disease. The execution of hand movements was found to be impaired in patients with Parkinson's disease as indicated by a reduced peak velocity of manual pointing responses when compared to age matched controls. By contrast, no differences were found in the dynamics of saccadic eye movements. This dissociation is consistent with the notion that the skeletomotor loop passes through the functionally corresponding portions of the basal ganglia independently of the oculomotor loop. Together, these results demonstrate that Parkinson's patients are able to generate multiple non-reflexive eye and hand movements and that the observed (manual) motor deficits are specific to the processes of motor execution.

Aged↗

The functional anatomy of single-word reading in patients with hemianopic and pure alexia.

We investigated single-word reading in normal subjects and patients with alexia following a left occipital infarct, using PET. The most posterior brain region to show a lateralized response was at the left occipitotemporal junction, in the inferior temporal gyrus. This region was activated when normal subjects, patients with hemianopic alexia and patients with an incomplete right homonymous hemianopia, but no reading deficit, viewed single words presented at increasing rates. This same area was damaged in a patient with pure alexia ("alexia without agraphia") and no hemianopia, who read words slowly using a letter-by-letter strategy. Although the exact level of the functional deficit is controversial, pure alexia is the result of an inability to map a percept of all the letters in a familiar letter string on to the mental representation of the whole word form. However, the commonest deficit associated with "pure" alexia is a right homonymous field defect; an impairment that may, by itself, interfere with single-word reading because of inability to see the letters towards the end of a word. The relative contributions of pure and hemianopic alexia in individual patients needs to be assessed, as the latter has been shown to respond well to specific rehabilitation programmes.

Adult↗

Impaired spatial working memory across saccades contributes to abnormal search in parietal neglect.

Visual neglect of left space following right parietal damage in humans involves a lateral bias in attention, apparent in many search tasks. We hypothesized that parietal neglect may also involve a failure to remember which locations have already been examined during visual search: an impairment in retaining searched locations across saccades. Using a new paradigm, we monitored gaze during search, while simultaneously probing whether observers judged they had found a new target, or judged instead that they were re-fixating a previously examined target. A patient with left neglect following focal right parietal infarction repeatedly re-fixated right locations. Critically, he often failed to remember that these locations had already been searched, treating old targets as new discoveries at an abnormal rate. In comparison, healthy age-matched control subjects rarely re-fixated targets, and mistook old targets as new targets even more rarely. The frequency of such mistakes in the parietal patient, for different conditions, correlated with the severity of his neglect. Control experiments indicated no perceptual localization deficit in non-search tasks. These results suggest a deficit in retaining searched locations across saccades in parietal neglect, in addition to the lateral spatial bias. Moreover, the former deficit exacerbates the latter, such that patients do not realize that the rightward locations favoured by their bias have already been examined during previous fixations and, for this reason, they saccade back to them repeatedly. The combination of the two deficits (a lateral bias plus a deficit in retaining locations already searched) may thus explain the pathological pattern of search that characterizes parietal neglect: why stimuli on the right are re-examined recursively, as if being searched for the first time, and hence why stimuli on the left continue to be ignored even with unlimited viewing time. These proposals accord with recent electrophysiological and functional imaging data, demonstrating posterior parietal involvement in the retention of target locations across saccades.

Aged↗

Selectively impaired reaction time in Parkinson's disease: persistent absence of simple reaction advantage in a patient with frontal complications.

The search for specific patterns of impaired reaction time in Parkinson's disease has yielded conflicting results. We propose subtypes that exhibit different patterns of impairment and report the case of a patient, Jobe, whose simple and binary choice reaction times were tested repeatedly in a variety of stimulus-response paradigms over a period of 4 years. Jobe consistently failed to exhibit the normal simple reaction advantage even though his choice reaction times fell well within the normal range. While his general intellectual status was above average, he had great difficulty with some neuropsychological tests. He was seldom able to acquire a new category in the Wisconsin Card Sort Test and also had difficulty with the Tower of London Test. We ascribe Jobe's selective impairment of simple reactions to an inability to engage in the off-line preparatory processing that confers an advantage on simple reactions.

Aged↗