Effects of incentives,age, and behavior on brain activation during inhibitory control: A longitudinal fMRI study

We investigated changes in brain function supporting inhibitory control under age-controlled incentivized conditions, separating age- and performance-related activation in an accelerated longitudinal design including 10- to 22-year-olds. Better inhibitory control correlated with striatal activation during neutral trials, while Age X Behavior interactions in the striatum indicated that in the absence of extrinsic incentives, younger subjects with greater reward circuitry activation successfully engage in greater inhibitory control. Age was negatively correlated with ventral amygdala activation during Loss trials, suggesting that amygdala function more strongly mediates bottom-up processing earlier in development when controlling the negative aspects of incentives to support inhibitory control. Together, these results indicate that with development, reward-modulated cognitive control may be supported by incentive processing transitions in the amygdala, and from facilitative to obstructive striatal function during inhibitory control.     

Maturation of executive function in autism.

BACKGROUND: Executive dysfunction has been reported at different ages in autism. It is not clear however, when this impairment emerges or how its expression is affected by development. METHODS: 61 non-mentally retarded autism participants (AUT) and 61 age, gender, and IQ matched typically developing participants (CON) were assessed with two oculomotor executive function tasks, the oculomotor delayed response task (ODR) and the antisaccade task (AS), as well as a visually-guided saccade sensorimotor task (VGS). RESULTS: The AUT group demonstrated impairments in response inhibition and spatial working memory at all ages tested. Developmental improvements in speed of sensorimotor processing and voluntary response inhibition were similar in both groups indicating sparing of some attentional control of behavior. Developmental progression in the speed of initiating a cognitive plan and maintaining information on line over time, however, was impaired in the AUT group indicating abnormal development of working memory. CONCLUSIONS: These results indicate that while executive dysfunction is present throughout development, there is evidence for both typical and atypical developmental progression of executive functions in autism. The plasticity suggested by the developmental improvements may have implications regarding appropriate developmental epochs and types of interventions aimed at enhancing cognitive capacities in individuals with autism.     

Development of prosaccade and antisaccade task performance in participants aged 6 to 26 years

There are few studies on the development of oculomotor functions during childhood. B. Fischer, M. Biscaldi, and S. Gezeck (1997) reported improvement of antisaccade task performance between ages 6 and 16 years. The present study is a replication and extension of those results. In three age groups (6-7, 10-11, 18-26 years), saccades during pro- and antisaccade tasks with 200-ms gap and overlap and during a fixation task were measured. Adults exhibited faster saccades and less prosaccades during the antisaccade tasks than 10-11-year-old children; these two groups had faster saccades during all tasks and less prosaccades during the anti- and the fixation task than 6-7-year-old subjects. Both children groups made more express saccades than adults. Results suggest different degrees of age-related improvement for different saccadic parameters, the effects being greatest for prosaccade inhibition during the antisaccade task and in line with the assumed protracted development of prefrontal functions.     

Error rate on the antisaccade task: heritability and developmental change in performance among preadolescent and late-adolescent female twin youth

We examined heritability of error rate on the antisaccade task among female twin youths. This task appears to be sensitive to prefrontal functioning, providing a measure of individual differences in inhibitory control associated with genetic risk for schizophrenia. The sample consisted of 674 11-year-olds and 616 17-year-olds, comprising the two cohorts of female twins from the Minnesota Twin Family Study, a population-based investigation of substance abuse and related psychopathology. We used biometric model-fitting methods to determine the relative magnitude of genetic and environmental influences on performance. In both age cohorts, the best fitting model contained additive genes and nonshared environment. Despite substantial age-related differences in mean performance levels (effect size = .81), additive genes accounted for greater than half the variance in performance in both age cohorts. These results are consistent with the hypothesis that antisaccade error rate might serve as an endophenotype for behavior disorders reflecting frontal lobe dysfunction or problems with inhibitory control.     

The effects of task instructions on pro and antisaccade performance

In the antisaccade task participants are required to overcome the strong tendency to saccade towards a sudden onset target, and instead make a saccade to the mirror image location. The task thus provides a powerful tool with which to study the cognitive processes underlying goal directed behaviour, and has become a widely used index of “disinhibition” in a range of clinical populations. Across two experiments we explored the role of top-down strategic influences on antisaccade performance by varying the instructions that participants received. Instructions to delay making a response resulted in a significant increase in correct antisaccade latencies and reduction in erroneous prosaccades towards the target. Instructions to make antisaccades as quickly as possible resulted in faster correct responses, whereas instructions to be as spatially accurate as possible increased correct antisaccade latencies. Neither of these manipulations resulted in a significant change in error rate. In a second experiment, participants made fewer errors in delayed pro and antisaccade tasks than in a standard antisaccade task. The implications of these results for current models of antisaccade performance, and the interpretation of antisaccade deficits in clinical populations are discussed.     

Antisaccade performance is related to genetic loading for schizophrenia

Disturbances of the oculomotor system are promising endophenotypes for schizophrenia. Increased error rates in the antisaccade task and prolonged antisaccade latencies have been found in patients with schizophrenia and their first degree relatives. We investigated oculomotor performance in 41 parents of schizophrenia patients and 22 controls with a prosaccade task and an antisaccade task. Parents were grouped into parents with a positive family history for schizophrenia (N = 9) and parents with a negative family history for schizophrenia (N = 32). An overlap-paradigm was applied; eye movements were recorded using infrared oculography. The combined group of parents made more antisaccade direction errors than controls (p = 0.005) and there was a linear increase in direction errors from controls via negative family history parents to positive family history parents (p = 0.008). Antisaccade latencies were prolonged in the combined parent group (p = 0.057) compared to controls and there was a linear increase in latency with genetic loading (p = 0.018). No group differences were found for prosaccade parameters. These results support the hypothesis that antisaccade impairment is associated with genetic loading for schizophrenia.     

Ketamine-induced distractibility: An oculomotor study in monkeys.

BACKGROUND: Administration of subanesthetic doses of ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist, induces a spectrum of behavioral disorders that are commonly observed in patients with schizophrenia. Although it has been demonstrated that poor antisaccade performance is a core dysfunction in schizophrenia, the ability of ketamine to induce an increased distractibility has not been demonstrated. The present study aimed to determine whether ketamine administration would reproduce the same antisaccade deficit as that observed in schizophrenic subjects. METHODS: We studied the effect of acute ketamine or saline administration on the performance of two monkeys trained on a reflexive visually guided saccade task and an antisaccade task. RESULTS: The main result is that ketamine administration induced a markedly increased antisaccade error rate and increased antisaccade latency, similar to that seen in schizophrenic subjects. Other impairments consisted of increased reflexive saccade latency and the presence of a gaze-evoked nystagmus. CONCLUSIONS: This study supports the validity of ketamine as a pharmacological model of schizophrenia. Based on the known pharmacological effects of ketamine, further studies should allow the investigation of the pharmacological basis of distractibility.     

Brief Reports: Top‐down control of visual sensory processing during an ocular motor response inhibition task

The study addressed whether top‐down control of visual cortex supports volitional behavioral control in a novel antisaccade task. The hypothesis was that anticipatory modulations of visual cortex activity would differentiate trials on which subjects knew an anti‐ versus a pro‐saccade response was required. Trials consisted of flickering checkerboards in both peripheral visual fields, followed by brightening of one checkerboard (target) while both kept flickering. Neural activation related to checkerboards before target onset (bias signal) was assessed using electroencephalography. Pretarget visual cortex responses to checkerboards were strongly modulated by task demands (significantly lower on antisaccade trials), an effect that may reduce the predisposition to saccade generation instigated by visual capture. The results illustrate how top‐down sensory regulation can complement motor preparation to facilitate adaptive voluntary behavioral control.     

The role of working memory and attentional disengagement on inhibitory control: effects of aging and Alzheimer's disease

Patients with Alzheimer''s disease have an impairment of inhibitory control for reasons that are currently unclear. Using an eye-tracking task (the gap-overlap paradigm), we examined whether the uncorrected errors relate to the task of attentional disengagement in preparation for action. Alternatively, the difficulty in correcting for errors may be caused by the working memory representation of the task. A major aim of this study was to distinguish between the effects of healthy aging and neurodegenerative disease on the voluntary control of saccadic eye movements. Using the antisaccade task (AST) and pro-saccade task (PST) with the ‘gap’ and ‘overlap’ procedures, we obtained detailed eye-tracking measures in patients, with 18 patients with probable Alzheimer''s disease, 25 patients with Parkinson''s disease and 17 healthy young and 18 old participants. Uncorrected errors in the AST were selectively increased in Alzheimer''s disease, but not in Parkinson''s disease compared to the control groups. These uncorrected errors were strongly correlated with spatial working memory. There was an increase in the saccade reaction times to targets that were presented simultaneously with the fixation stimulus, compared to the removal of fixation. This ‘gap’ effect (i.e. overlap–gap) saccade reaction time was elevated in the older groups compared to young group, which yielded a strong effect of aging and no specific effect of neurodegenerative disease. Healthy aging, rather than neurodegenerative disease, accounted for the increase in the saccade reaction times to the target that are presented simultaneously with a fixation stimulus. These results suggest that the impairment of inhibitory control in the AST may provide a convenient and putative mark of working memory dysfunction in Alzheimer''s disease.