Abnormal negative feedback processing in first episode schizophrenia: evidence from an oculomotor rule switching task.

BACKGROUND: Previous studies have shown that patients with schizophrenia are impaired on executive tasks, where positive and negative feedbacks are used to update task rules or switch attention. However, research to date using saccadic tasks has not revealed clear deficits in task switching in these patients. The present study used an oculomotor 'rule switching' task to investigate the use of negative feedback when switching between task rules in people with schizophrenia. METHOD: A total of 50 patients with first episode schizophrenia and 25 healthy controls performed a task in which the association between a centrally presented visual cue and the direction of a saccade could change from trial to trial. Rule changes were heralded by an unexpected negative feedback, indicating that the cue-response mapping had reversed. RESULTS: Schizophrenia patients were found to make increased errors following a rule switch, but these were almost entirely the result of executing saccades away from the location at which the negative feedback had been presented on the preceding trial. This impairment in negative feedback processing was independent of IQ. CONCLUSIONS: The results not only confirm the existence of a basic deficit in stimulus-response rule switching in schizophrenia, but also suggest that this arises from aberrant processing of response outcomes, resulting in a failure to appropriately update rules. The findings are discussed in the context of neurological and pharmacological abnormalities in the conditions that may disrupt prediction error signalling in schizophrenia.

The value of radio-anatomical features on non-contrast CT scans in localizing the source in aneurysmal subarachnoid haemorrhage.

Identification of the source of subarachnoid haemorrhage (SAH) can be a challenge in the presence of multiple aneurysms. This study was carried out to assess whether radioanatomical features on noncontrast enhanced computerised tomography (CT) scans may be of value in localizing ruptured intracranial aneurysms. The diagnostic CT scans of 56 consecutive patients, investigated for SAH with cerebral angiography, over a period of six months were available for review. Various radioanatomical features were assessed: (1) pattern of subarachnoid blood (e.g. predominant site and location near major vessel bifurcation), (2) presence of intraparenchymal haematoma, (3) presence of aneurysm contour and (4) hydrocephalus. On the basis of the findings an estimation of the anatomical location of the source of bleeding was made and then compared with the angiogram findings to which the reviewer was blinded. The location of the aneurysm was correctly identified in 89.5% of cases. Careful analysis of the pattern of bleeding was essential for the successful localization of the aneurysm in all these cases. The presence of an aneurysm contour was also associated with correct identification of the source of bleeding (chi(2) = 6.067, P = 0.02). Our findings suggest that radioanatomical features on CT scans in SAH can be a valuable aid in the correct identification of the location of the ruptured aneurysm. This would be of particular significance in the presence of multiple intracranial aneurysms.

Predictive learning, prediction errors, and attention: evidence from event-related potentials and eye tracking.

Prediction error ("surprise") affects the rate of learning: We learn more rapidly about cues for which we initially make incorrect predictions than cues for which our initial predictions are correct. The current studies employ electrophysiological measures to reveal early attentional differentiation of events that differ in their previous involvement in errors of predictive judgment. Error-related events attract more attention, as evidenced by features of event-related scalp potentials previously implicated in selective visual attention (selection negativity, augmented anterior N1). The earliest differences detected occurred around 120 msec after stimulus onset, and distributed source localization (LORETA) indicated that the inferior temporal regions were one source of the earliest differences. In addition, stimuli associated with the production of prediction errors show higher dwell times in an eye-tracking procedure. Our data support the view that early attentional processes play a role in human associative learning.

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.

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.

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.

"Bottom-up" and "top-down" effects on reading saccades: a case study.

OBJECTIVE: To investigate the role right foveal/parafoveal sparing plays in reading single words, word arrays, and eye movement patterns in a single case with an incongruous hemianopia. METHODS: The patient, a 48-year-old right handed male with a macular sparing hemianopia in his left eye and a macular splitting hemianopia in his right eye, performed various reading tasks. Single word reading speeds were monitored using a "voice-trigger" system. Eye movements were recorded while reading three passages of text, and PET data were gathered while the subject performed a variety of reading tasks in the camera. RESULTS: The patient was faster at reading single words and text with his left eye compared with his right. A small word length effect was present in his right eye but not his left. His eye movement patterns were more orderly when reading text with his left eye, making fewer saccades. The PET data provided evidence of "top-down" processes involved in reading. Binocular single word reading produced activity in the representation of foveal V1 bilaterally; however, text reading with the left eye only was associated with activation in left but not right parafoveal V1, despite there being visual stimuli in both visual fields. CONCLUSIONS: The presence of a word length effect (typically associated with pure alexia) can be caused by a macular splitting hemianopia. Right parafoveal vision is not critically involved in single word identification, but is when planning left to right reading saccades. The influence of top-down attentional processes during text reading can be visualised in parafoveal V1 using PET.

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.

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.

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.

The strategic control of gaze direction in the Tower-of-London task.

In this paper, we describe 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 (TOL) task. We showed subjects a series of pictures depicting two arrangements of colored balls in pockets within the upper and lower halves of a computer display. The task was to plan (but not to 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 minimum number of moves required for problem solution. We report that subjects are more likely to look towards the Goalspace in the initial period after picture presentation, but bias gaze towards the Workspace during the middle of trials. Towards the end of a trial, subjects are once again more likely to fixate the Goalspace. This pattern is found regardless of whether the subjects solve problems by rearranging the balls in the lower or upper visual fields, demonstrating that this strategy correlates with discrete phases in problem solving. A second experiment showed that efficient planners direct their gaze selectively towards the problem critical balls in the Workspace. In contrast, individuals who make errors spend more time looking at irrelevant items and are strongly influenced by the movement strategy needed to solve the preceding problem. We conclude that efficient solution of the TOL requires the capacity to generate and flexibly shift between control sets, including those underlying ocular scanning. The role of working memory and the prefrontal cerebral cortex in the task are discussed.

Disorders of higher visual function and hemi-spatial neglect.

Lesions of the extrastriate cerebral cortex result in disorders of vision, which reveal two cortical processing streams extending ventrally and dorsally from the primary visual cortex. Current theories emphasize the visual perceptual and visuomotor specialization of the ventral and dorsal streams, respectively. Recent investigations of hemi-spatial neglect suggest that the inferior parietal region may lie at the junction of the visual and motor processing pathways.

Impaired reading in patients with right hemianopia.

A left occipital stroke may result in alexia for two reasons, which may coexist depending on the distribution of the lesion. A lesion of the left lateroventral prestriate cortex or its afferents impairs word recognition ("pure" alexia). If the left primary visual cortex or its afferents are destroyed, resulting in a complete right homonymous hemianopia, rightward saccades during text reading are disrupted ("hemianopic" alexia). By using functional imaging, we showed two separate but interdependent systems involved in reading. The first, subserving word recognition, involved the representation of foveal vision in the left and right primary visual cortex and the ventral prestriate cortex. The second system, responsible for the planning and execution of reading saccades, consisted of the representation of right parafoveal vision in the left visual cortex, the bilateral posterior parietal cortex (left > right), and the frontal eye fields (right > left). Disruption of this distributed neural system was demonstrated in patients with severe right homonymous hemianopia, commensurate with their inability to perform normal reading eye movements. Text reading, before processes involved in comprehension, requires the integration of perceptual and motor processes. We have demonstrated these distributed neural systems in normal readers and have shown how a right homonymous hemianopia disrupts the motor preparation of reading saccades during text reading.

Eye movements and spatial working memory in Parkinson's disease.

Mechanisms of spatial working memory and eye movement control were investigated in eight mild to moderate Parkinson's disease patients (PDs). Subjects were presented with a sequence of four targets which had to be memorized and then recalled by moving their eyes to fixate the four locations in the correct order. Two variations on this procedure were used in which either a different sequence of lights was presented on each trial, or an identical sequence of lights was repeated on each trial. In both conditions subjects made memory-guided eye movements in the dark, without any visual cues to eye movement accuracy or the locations of the previously illuminated lights. Analysis of the amplitude of the primary eye movement and final eye position for each step in the sequence showed that PDs made several discrete saccadic eye movements of reduced amplitude before reaching the final eye position (multi-stepping). When a novel target sequence had to be memorized on each trial, the final eye position reached by PDs for each location was also found to undershoot relative to controls. In contrast, when an identical sequence of targets was repeated on each trial, PDs' final eye position was found to be normal, although primary movement amplitudes were still reduced. PDs showed no multi-stepping and normal final eye position gain under conditions for which the target lights in the sequence were illuminated during movement execution. PDs also made an increased proportion of overt errors in target sequence recall. Parallel neuropsychological testing in PDs and controls revealed that error rates in the sequential memory-guided saccade task were significantly correlated with performance in a task thought to be sensitive to spatial working memory dysfunction. The findings suggest that short-term spatial memory representations are disrupted in the early stages of PD.

Attentional localization prior to simple and directed manual responses.

The relationship between attention and the programming of motor responses was investigated, using a paradigm in which the onsets of targets for movements were preceded by peripheral attentional cues. Simple (button release) and reaching manual responses were compared under conditions in which the subjects either made saccades toward the target location or refrained from making eye movements. The timing of the movement onset was used as the dependent measure for both simple and reaching manual responses. Eye movement latencies were also measured. A follow-up experiment measured the effect of the same peripheral cuing procedure on purely visual processes, using signal detection measures of visual sensitivity and response bias. The results of the first experiment showed that reaction time (RT) increased with the distance between the cued and the target locations. Stronger distance effects were observed when goal-directed responses were required, which suggests enhanced attentional localization of target positions under these conditions. The requirement to generate an eye movement response was found to delay simple manual RTs. However, mean reaching RTs were unaffected by the eye movement condition. Distance gradients on eye movement latencies were relatively shallow, as compared with those on goal-directed manual responses. The second experiment showed that the peripheral cue had only a very small effect on visual detection sensitivity in the absence of directed motor responses. It is concluded that cue-target distance effects with peripheral cues are modulated by the motor-programming requirements of the task. The effect of the peripheral cue on eye movement latencies was qualitatively different from that observed on manual RTs, indicating the existence of separate neural representations underlying both response types. At the same time, the interactions between response modalities are consistent with a supramodal representation of attentional space, within which different motor programs may interact.

Saccadic eye movement and working memory deficits following damage to human prefrontal cortex.

A patient with a lesion confined largely to the right inferior frontal gyrus was found to be impaired on tests of spatial working memory and executive functioning. By contrast, his pattern recognition was good. The patient's selective impairments are consistent with the view that prefrontal cortex contributes to processes involved in spatial working memory. The patient was also tested on a range of oculomotor paradigms, some of which required the temporary suppression of a saccadic response. He was unable to suppress making contra- or ipsilesional reflexive glances to peripheral stimuli on the "anti-saccade" paradigm, but his performance improved on delayed saccade, memory-guided saccade and fixation tasks. Although reflexive glances were observed under these conditions they occurred more frequently in response to contralesional stimuli than ipsilesional ones. Furthermore, the patient had no difficulty in performing anti-point movements with his ipsilesional hand. Thus, his inability to suppress reflexive glances on the anti-saccade task is not due to a generalised problem of "distractibility". The patient's deficits are discussed in terms of models of anti-saccade generation and are related to recent findings regarding the role of prefrontal cortex in working memory and visual attention.