Smooth pursuit eye movements, attention, and schizophrenia

In previous studies, smooth pursuit eye movements (SPEM) have been shown to be disordered in about 70% of schizophrenics and about 45% of their first-degree relatives. In this report, the role of attention in these eye movements is addressed in three experiments (using as subjects schizophrenics, their first-degree relatives, and normals administered chloral hydrate) that recruit focused attention to the task. These studies show that voluntary attention in the form of inattention, "heedless negligence," or failure to cooperate, is not the specific attentional quality that is disordered in SPEM of schizophrenics and their relatives. Rather, the data both indicate that nonvoluntary attending is specifically disordered in these persons, and implicate a neurophysiological substrate that can be described as a failure of inhibitory, synchronizing integrating systems which may be located in the brain stem.     

Smooth pursuit eye movements to extraretinal motion signals: deficits in relatives of patients with schizophrenia

BACKGROUND: Although mounting evidence supports the idea that smooth pursuit abnormality marks the genetic liability to schizophrenia, the precise ocular motor mechanism underlying the abnormality remains unknown. Based on recent findings in schizophrenia, we hypothesize that subtle deficits in the ability to hold online and/or use extraretinal motion information underlie the pursuit abnormality in vulnerable individuals. METHODS: The hypothesis was tested in 69 first-degree, biological relatives of probands with schizophrenia; 26 relatives had schizophrenia spectrum personalities (SSP). Subjects recruited from the community (n=71; 29 with SSP), without a known family history of psychosis, constituted the comparison groups. The traditional smooth pursuit gain measure, which is a ratio of smooth pursuit eye velocity in response to both retinal and extraretinal motion signals and the target velocity, was obtained. In addition, newly developed measures of predictive smooth pursuit (ie, in the presence of only extraretinal motion signals) were obtained. The latter measures were evaluated after the current retinal motion signals were made unavailable by briefly making the target invisible. RESULTS: Relatives, particularly those with SSP, showed significantly poorer predictive pursuit response to extraretinal motion signals (F(2,136)=6.51, P<.005), compared with the community subjects. However, the traditional smooth pursuit gain in response to both retinal and extraretinal motion signals was not different between groups. CONCLUSIONS: These results suggest that relatives of patients with schizophrenia, particularly those with SSP, have specific deficits in predictive pursuit based on only extraretinal motion signals. Normal smooth pursuit gain in response to both retinal and extraretinal motion signals is likely due to compensation based on retinal motion information. The latter suggests normal retinal motion processing and smooth pursuit motor output.     

Smooth pursuit eye movement and schizotypy in the community.

Deficits in smooth pursuit eye movements are well documented in schizophrenia and schizotypic psychopathology. The status of eye tracking dysfunction (ETD) as an endophenotype for schizophrenia liability is relatively robust. However, the relation of ETD to schizophrenia-related deviance in the general population has not been confirmed. This study examined smooth pursuit eye tracking and schizotypal personality features in the general population. Smooth pursuit eye movement and schizotypal features were measured in 300 adult community subjects. The sample included both sexes, subjects with a wide age and educational range, and subjects with no prior history of psychosis. Primary outcome measures were peak gain (eye velocity/target velocity), catch-up saccade rate, and schizotypal feature scores. Total schizotypal features were significantly associated with decreased peak gain and were associated at the trend level with increased catch-up saccade rate. These associations were essentially unchanged after controlling for age, sex, and intellectual level effects. These data confirm a hypothesized association between schizotypal features and poorer eye tracking performance (principally, peak gain) in the general population as well as support the conceptualization of ETD as an endophenotype for schizophrenia liability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interpreting open- and closed-loop transfer relations between cardiorespiratory parameters: lessons learned from a computer model of beat-to-beat cardiovascular regulation

A computer model of cardiovascular control has been developed based on the response characteristics of cardiovascular control components derived from experiments in animals and humans. Results from the model were compared to those obtained experimentally in humans, and the similarities and differences were used to identify both the strengths and inadequacies of the concepts used to form the model. Findings were confirmatory of some concepts but contrary to some which are firmly held in the literature, indicating that understanding the complexity of cardiovascular control probably requires a combination of experiments and computer models which integrate multiple systems and allow for determination of sufficiency and necessity.     

Oculomotor abnormalities in schizophrenia: a critical review

Oculomotor abnormalities, particularly in smooth pursuit tracking, are one of the most widely investigated biological markers of schizophrenia. However, despite the wealth of published data, important questions concerning the exact nature of these abnormalities remain unanswered. Many of the studies use unreliable methodology, and few attempts have been made to interpret the observed oculomotor dysfunction in terms of current understanding of eye movement physiology. Also, the potential effects of antipsychotic medication have been poorly addressed. Recent research, using more reliable measurement techniques and novel saccadic paradigms are producing important results and may provide a more productive framework for future studies of oculomotor abnormalities in schizophrenia.     

Smooth pursuit in 1- to 4-month-old human infants

The ability of human infants < or = 4 months of age to pursue objects smoothly with their eyes was assessed by presenting small target spots moving with hold-ramp-hold trajectories at ramp velocities of 4-32 deg/sec. Infants as young as 1 month old followed such target motions with a combination of smooth-pursuit and saccadic eye movements interrupted occasionally by periods when the eyes remained stationary. The slowest targets produced variable performance, but targets moving 8-32 deg/sec produced consistent pursuit behavior, even in the youngest infants. By the fourth month, eye-movement latency decreased and smooth-pursuit gain and the percentage of smooth pursuit per trial increased for all target velocities, though these measures had not yet reached adult levels.     

Structural brain abnormalities in schizophrenia: a family study

Structural brain abnormalities such as ventricular enlargement are robust correlates of schizophrenia, but the degree of difference compared with unrelated normal controls is only moderate (< 1 standard deviation), and only 40% of patients have values on these measures that fall outside of the normal distribution. Family studies can help to clarify the meaning of this overlap by controlling for some of the non-schizophrenia-related genetic variation in neuroanatomical traits. Computerized tomographic scans of the brain were used to measure ventricular and sulcal cerebrospinal fluid (CSF) to brain ratios (VBR and SBR) for each hemisphere in 16 pairs of discordant siblings from the Copenhagen Schizophrenia High-Risk Project. Schizophrenics' values for VBR and SBR exceeded those of their nonschizophrenic siblings in 75% of the pairs; on average, patients' values on these measures were 1 and 5 standard deviations larger, respectively, than those of their nonschizophrenic siblings. Sulcal and left hemisphere effects were significantly more pronounced than ventricular and right hemisphere effects. After controlling for between-family variation, structural brain abnormalities appear to be more prevalent and more pronounced in schizophrenia than has previously been assumed, with relatively greater deviation observed for cortical and left hemisphere measures of CSF space enlargement.     

Smooth pursuit eye movement deficits after pontine nuclei lesions in humans

Eye movements were recorded electroculographically in four patients with basal pontine lesions, demonstrated by MRI. The most prominent eye movement abnormality observed was mild to severe impairment of smooth pursuit and optokinetic nystagmus, mainly ipsilateral to the lesion. This abnormality is thought to result from damage to the pontine nuclei, which form a crucial relay between the cerebral cortex and the cerebellum controlling smooth pursuit. Abnormalities of saccades and the vestibulo-ocular reflex in one patient are also discussed.     

Developmental brain abnormalities in schizophrenia: contributions of genetic and perinatal factors

We report a patient who had refractory Hodgkin's disease and who received an autologous bone marrow transplantation and 8 months later developed abdominal pain associated with acute colonic dilation. The course of the patient was rapidly fatal due to a lobar pneumonia. Autopsy revealed signs of disseminated herpesvirus infection with marked hemorrhagic infarction of celiac sympathetic ganglia. This finding supports the hypothesis that denervation caused by virus reactivation and secondary hemorrhage is a main mechanism of acute colonic pseudoobstruction.     

Anticipatory saccades during smooth pursuit eye movements and familial transmission of schizophrenia

BACKGROUND: Smooth pursuit eye movement (SPEM) abnormalities are a putative marker of genetic risk for schizophrenia. Accurate SPEM performance requires the subject to activate neural systems responsible for smooth pursuit tracking, while simultaneously suppressing activity of neurons responsible for saccadic movements that would move the eye ahead of the target. This study examined whether specific aspects of SPEM dysfunction cosegregate with genetic risk in parents of schizophrenic probands. METHODS: Eighteen probands and their parents had SPEM recorded. Parents with an ancestral history of schizophrenia were hypothesized to be more likely than their spouses without such a history to carry a genetic risk for schizophrenia. RESULTS: Ten families had a single parent with a positive ancestral history for schizophrenia. The frequency of anticipatory saccades, which were mostly small, and the fraction of total eye movement that they represented were the only measures that differentiated the more likely genetic carrier parents in these families from their spouses and age-matched normals. CONCLUSIONS: Failure to suppress saccadic anticipation of target motion during smooth pursuit appears an aspect of SPEM dysfunction related to presumed genetic risk for schizophrenia.     

Persistence of maladaptive responses in schizophrenia.

30 schizophrenic patients and 30 psychiatric aides were required in 4 experimental tasks to change their responses to meet changing conditions. It was hypothesized that (a) schizophrenic patients are more likely than normals to continue a response after it becomes ineffective; (b) the persistence of the maladaptive response is a function of the severity of schizophrenia. As predicted, the patients persisted longer than the aides in the first learned but later maladaptive responses, and there was some evidence that degree of resistance to change was related to the severity of schizophrenia in the patient. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurocognitive abnormalities during comprehension of real-world goal-directed behaviors in schizophrenia.

Origins of impaired adaptive functioning in schizophrenia remain poorly understood. Behavioral disorganization may arise from an abnormal reliance on common combinations between concepts stored in semantic memory. Avolition–apathy may be related to deficits in using goal-related requirements to flexibly plan behavior. The authors recorded event-related potentials (ERPs) in 16 patients with medicated schizophrenia and 16 healthy controls in a novel video paradigm presenting congruous or incongruous objects in real-world activities. All incongruous objects were contextually inappropriate, but the incongruous scenes varied in comprehensibility. Psychopathology was assessed with the Scales for the Assessment of Positive and Negative Symptoms (SAPS/SANS) and the Brief Psychiatric Rating Scale. In patients, an N400 ERP, thought to index activity in semantic memory, was abnormally enhanced to less comprehensible incongruous scenes, and larger N400 priming was associated with disorganization severity. A P600 ERP, which may index flexible object–action integration based on goal-related requirements, was abnormally attenuated in patients, and its smaller magnitude was associated with the SANS rating of impersistence at work or school (goal-directed behavior). Thus, distinct neurocognitive abnormalities may underlie disorganization and goal-directed behavior deficits in schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuronal responses in visual areas MT and MST during smooth pursuit target selection

We recorded the activity of single neurons in the middle temporal (MT) and middle superior temporal (MST) visual areas in two macaque monkeys while the animals performed a smooth pursuit target selection task. The monkeys were presented with two moving stimuli of different colors and were trained to initiate smooth pursuit to the stimulus that matched the color of a previously given cue. We designed these experiments so that we could separate the component of the neuronal response that was driven by the visual stimulus from an extraretinal component that predicted the color or direction of the selected target. We found that for all cells in MT and MST the response was primarily determined by the visual stimulus. However, 14% (8 of 58) of MT neurons and 26% (22 of 84) of MST neurons had a small predictive component that was significant at the P < or = 0.05 level. In some cells, the predictive component was clearly related to the color of the intended target, but more often it was correlated with the direction of the target. We have previously documented a systematic shift in the latency of smooth pursuit that depends on the relative direction of motion of the two stimuli. We found that neither the latency nor the amplitude of neuronal responses in MT or MST was correlated with behavioral latency. These results are consistent with a model for target selection in which a weak selection bias for the intended target is amplified by a competitive network that suppresses motion signals related to the nonintended stimulus. It is possible that the predictive component of neuronal responses in MT and MST contributes to the selection bias. However, the strength of the selection bias in MT and MST is not sufficient to account for the high degree of selectivity shown by pursuit behavior.     

Possible relevance of phospholipid abnormalities and genetic interactions in psychiatric disorders: the relationship between dyslexia and schizophrenia

The fatty acids of cell membrane phospholipids are essential for normal membrane structures, for the functioning of membrane-bound and membrane-associated proteins and for normal cell-signalling responses. In dyslexia, there is evidence for reduced incorporation of docosahexaenoic acid and arachidonic acid into cell membranes, while in schizophrenia, there is evidence for an increased rate of docosahexaenoic acid and arachidonic acid loss from membranes because of enhanced phospholipase A2 activity. The presence of both defects will cause a much greater degree of abnormality than either one alone. It is hypothesized that unequivocal clinical schizophrenia may occur when both genes are present in the same individual. The dyslexia gene along will produce dyslexia while the schizophrenia gene alone may produce bipolar or schizoaffective disorders. These proposals could explain: 1. The reduced asymmetry of the brain, especially of the planum temporale in both schizophrenia and dyslexia; 2. The schizotypal personality characteristics of dyslexics; 3. The increased risks of dyslexia in families with a schizophrenic proband; 4. The increased risks of bipolar and schizoaffective disorders in families with a schizophrenic proband; 5. The earlier onset and possibly increased severity of both disorders in males since females have a lower requirement for arachidonic acid and docosahexaenoic acid; 6. The absence of selective pressure against schizophrenia since reproduction would be impaired only when the schizophrenic gene coexisted with a dyslexic gene. The schizophrenic gene alone might even lead to improved reproductive performance.     

Oesophageal reflex responses: abnormalities of the enteric nervous system in patients with oesophageal symptoms

An intraluminal balloon was used to study the peristaltic reflex, which is mediated by the intrinsic nerves of the oesophagus. Serial balloon distension was performed in nine asymptomatic volunteers and 133 patients with oesophageal symptoms. Eight of the volunteers had a normal response with proximal stimulation and distal inhibition of motility. Only 42 patients (31.6 per cent) had a normal response. The commonest abnormal response (39.1 per cent) was some form of failure of the distal inhibitory reflex. Other patterns of abnormality were an unresponsive oesophagus (15.8 per cent) with no motility change during balloon inflation, or spasm (13.5 per cent) proximal to the balloon. These alterations of secondary peristaltic activity suggest that there are abnormalities of the intrinsic (enteric) nerves of the oesophagus. Different abnormalities were found in patients with similar symptoms. Awareness of this difference might allow a more rational approach to treatment. This hypothesis was tested in a small pilot study treating functional dysphagia with cisapride. Three of nine patients had marked symptomatic improvement within 4 weeks and all three had an unresponsive oesophagus. The remaining six patients, who had failure of distal inhibition or a normal response, did not improve.     

The epidemiology of peritonitis in acute peritoneal dialysis: a comparison between open- and closed-drainage systems

We performed a prospective study to examine the epidemiology and microbiology of peritonitis complicating acute intermittent peritoneal dialysis (IPD) performed in an in-hospital setting for the management of acute and chronic renal failure and to see the effect of a closed-drainage system on altering the frequency and cause of peritonitis. Over a 15-month period, 79 patients were treated with acute IPD for a total of 136 treatments each ranging in length from 2 to 40 days (median, 4 days). The majority of cases had acute renal failure (ARF; 65%) and were treated in intensive care units (ICUs; 74%) with serious comorbid conditions (60%). About half were treated with a two-bag, ventable (open)-drainage system with unprotected spikes, and the other half were treated with a single-bag, spike-protected, closed-drainage system. There were 27 cases of peritonitis for a rate of 4.5 cases/100 patient-days at risk. About half were gram-positive infections; the remainder were gram-negative or mixed (25%) or Candida sp (25%). The use of a closed-drainage system reduced the incidence of system-related peritonitis from 3.6 to 1.5 cases/100 patient-days. There was a high rate of peritonitis in the first 48 hours of treatment, which fell to a low stable rate thereafter and remained so for up to 15 days of continuous IPD. The use of a closed-drainage system eliminated the early (< 48 hours) high rate of peritonitis and maintained a low constant rate of peritonitis throughout treatment. There was an association of ARF and severe comorbid disease with more virulent organisms (gram-negative, mixed, and Candida sp), which, in turn, were both associated with antecedent broad-spectrum antibiotic therapy. Random positive surveillance cultures showed a frequency distribution similar to that of peritonitis cases over the duration of treatment, but with less virulent organisms. Peritonitis in acute IPD occurs when large or repeated inocula of organisms from the prevailing flora overwhelm the peritoneal immune clearance mechanisms. Prolonged courses of broad-spectrum antibiotic therapy provide no protection, but shift the resulting infecting flora toward more virulent pathogens. A closed-drainage system provides one method to reduce the frequency of peritoneal contamination.     

Pupillary responses index overload of working memory resources in schizophrenia.

The authors examined the hypothesis that schizophrenia patients have reduced availability of working memory resources by using pupillary responses as an index of resource overload. Pupillary responses were recorded during a verbal working memory task (digit recall) in 24 schizophrenia patients and 32 normal controls. Pupil size increased with increased processing load (digit-span length) but changed little or declined when processing demands exceeded available resources (overload). The schizophrenia patients showed impaired digit recall and abnormally small pupillary responses during digit presentation only in the higher processing load conditions, but they showed abnormally small pupillary responses during digit retrieval in all processing load conditions. The results suggest reduced availability of slave store and central executive working memory resources in schizophrenia. This study serves as an example of how pupillography methods can be used to test current hypotheses regarding overload of cognitive capacities in schizophrenia patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Eye tracking dysfunction in schizophrenia: Characterization of component eye movement abnormalities, diagnostic specificity, and the role of attention.

To characterize oculomotor components and diagnostic specificity of eye tracking abnormalities in schizophrenia, we examined a large consecutively admitted series of psychotic patients and matched controls. The most common abnormality in schizophrenic patients was low gain (slow) pursuit eye movements (47% of cases). Pursuit and saccadic eye movement abnormalities were no more severe in schizophrenic Ss than in those with affective psychoses, except that high rates of catch-up saccades were unique to schizophrenic Ss (17% of cases). These findings indicate that impaired pursuit eye movements are a major cause of eye tracking impairments in schizophrenia, that tracking dysfunctions commonly occur in affective psychoses, and that markedly high rates of catch-up saccades during eye tracking may be specific to schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Controlled information processing resources and the development of automatic detection responses in schizophrenia.

The relation between resource limitations and the type of processing (automatic vs controlled) on a multiple-frame search task (MFST) was examined in 15 schizophrenic and 15 normal control Ss. After 320 trials of consistently mapped practice, the patients' detection accuracy was normalized, and the effect of processing load (letter array size) on their detection accuracy was eliminated, which suggests automatization. Changes in load effects with practice could not be used as an index of automatization in control Ss, because of their unexpected lack of load effects at the beginning of practice. In a dual-task (MFST during auditory shadowing) condition after MFST practice, patients' MFST accuracy deteriorated nonsignificantly, and patients' shadowing declined significantly. The findings suggest schizophrenics have reduced available processing resources, but research is needed to determine whether this is due to abnormal automatization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)