Monica Biscaldi

On the development of voluntary and reflexive components in human saccade generation

The saccadic performance of a large number (n = 281) of subjects of different ages (8-70 years) was studied applying two saccade tasks: the prosaccade overlap (PO) task and the antisaccade gap (AG) task. From the PO task, the mean reaction times and the percentage of express saccades were determined for each subject. From the AG task, the mean reaction time of the correct antisaccades and of the erratic prosaccades were measured. In addition, we determined the error rate and the mean correction time, i.e. the time between the end of the first erratic prosaccade and the following corrective antisaccade. These variables were measured separately for stimuli presented (in random order) at the right or left side. While strong correlations were seen between variables for the right and left sides, considerable side asymmetries were obtained from many subjects. A factor analysis revealed that the seven variables (six eye movement variables plus age) were mainly determined by only two factors, V and F. The V factor was dominated by the variables from the AG task (reaction time, correction time, error rate) the F factor by variables from the PO task (reaction time, percentage express saccades) and the reaction time of the errors (prosaccades!) from the AG task. The relationship between the percentage number of express saccades and the percentage number of errors was completely asymmetric: high numbers of express saccades were accompanied by high numbers of errors but not vice versa. Only the variables in the V factor covaried with age. A fast decrease of the antisaccade reaction time (by 50 ms), of the correction times (by 70 ms) and of the error rate (from 60 to 22%) was observed between age 9 and 15 years, followed by a further period of slower decrease until age 25 years. The mean time a subject needed to reach the side opposite to the stimulus as required by the antisaccade task decreased from approximately 350 to 250 ms until age 15 years and decreased further by 20 ms before it increased again to approximately 280 ms. At higher ages, there was a slight indication for a return development. Subjects with high error rates had long antisaccade latencies and needed a long time to reach the opposite side on error trials. The variables obtained from the PO task varied also significantly with age but by smaller amounts. The results are discussed in relation to the subsystems controlling saccade generation: a voluntary and a reflex component the latter being suppressed by active fixation. Both systems seem to develop differentially. The data offer a detailed baseline for clinical studies using the pro- and antisaccade tasks as an indication of functional impairments, circumscribed brain lesions, neurological and psychiatric diseases and cognitive deficits.

Separate populations of visually guided saccades in humans: reaction times and amplitudes

SummaryThe saccadic eye movements of 20 naive adults, 7 naive teenagers, 12 naive children, and 4 trained adult subjects were measured using two single target saccade tasks; the gap and the overlap task. In the gap task, the fixation point was switched off before the target occurred; in the overlap task it remained on until the end of each trial. The target position was randomly selected 4° to the left or 4° to the right of the fixation point. The subjects were instructed to look at the target when it appeared, not to react as fast as possible. They were not given any feedback about their performance. The results suggest that, in the gap task, most of the naive subjects exhibit at least two (the teenagers certainly three) clearly separated peaks in the distribution of the saccadic reaction times. The first peak occurs between 100 and 135 ms (express saccades), the second one between 140 and 180 ms (fast regular), and a third peak may follow at about 200 ms (slow regular). Other subjects did not show clear signs of two modes in the range of 100 to 180 ms, and still others did not produce any reaction times below 135 ms. In the overlap task as well three or even more peaks were obtained at about the same positions along the reaction time scale of many, but not all subjects. Group data as well as those of individual subjects were fitted by the superposition of three gaussian functions. Segregating the reaction time data into saccades that over- or undershoot the target indicated that express saccades almost never overshoot. The results are discussed in relation to the different neural processes preceding the initiation of visually-guided saccades.

Voluntary Saccadic Control in Dyslexia

The role of eye-movement control in dyslexia is still unclear. Recent studies, however, confirmed that dyslexics show poor saccadic control in single and sequential target tasks. In the present study we investigated whether dyslexic subjects are impaired on an antisaccade task requiring saccades against the direction of a stimulus. Altogether, 620 subjects between the ages of 7 and 17 years were classified as dyslexics (N = 506) or control subjects (N = 114) on the grounds of the discrepancy between their intellectual abilities and reading/spelling achievements. All subjects performed an overlap prosaccade and a gap antisaccade task with 100 trials to each side of stimulation in random order. Variables analysed were the overall saccadic reaction time of both tasks; and from the antisaccade task the number of errors (prosaccades), the number of corrected errors, and the number of trials in which the subjects still failed to reach the side opposite the stimulus even after two saccades. An analysis of variance was carried out taking into account the development of saccadic behaviour with age and the differences between the groups. The results confirm development of saccade control with age, especially in the voluntary component (a frontal-lobe function) for both groups, but indicate that the antisaccade task performance, as measured by the error and the correction rate, is significantly worse in the dyslexic group at ages above 8 years. Up to 50% of the dyslexics performed the antisaccade task 1.5 standard deviations below the mean of the controls.

Saccadic Eye Movements of Dyslexic and Normal Reading Children

Twenty-four children made saccades in five noncognitive tasks. Two standard tasks required saccades to a single target presented randomly 4 deg to the right or left of a fixation point. Three other tasks required sequential saccades from the left to the right. 75 parameters of the eye-movement data were collected for each child. On the basis of their reading, writing, and other cognitive performances, twelve children were considered dyslexic and were divided into two groups (D1 and D2). Group statistical comparisons revealed significant differences between control and dyslexic subjects. In general, in the standard tasks the dyslexic subjects had poorer fixation quality, failed more often to hit the target at once, had smaller primary saccades, and had shorter reaction times to the left as compared with the control group. The control group and group D1 dyslexics showed an asymmetrical distribution of reaction times, but in opposite directions. Group D2 dyslexics made more anticipatory and express saccades, they undershot the target more often in comparison with the control group, and almost never overshot it. In the sequential tasks group D1 subjects made fewer and larger saccades in a shorter time and group D2 subjects had shorter fixation durations than the subjects of the control group.

Impaired induction of long‐term potentiation‐like plasticity in patients with high‐functioning autism and Asperger syndrome

Aim  We aimed to investigate the induction of long‐term potentiation (LTP)‐like plasticity by paired associative stimulation (PAS) in patients with high‐functioning autism and Asperger syndrome (HFA/AS).

On the Temporal Characteristics of Performance Variability in Attention Deficit Hyperactivity Disorder (ADHD)

Increased intra-subject variability of reaction times (ISV-RT) is one of the most consistent findings in attention-deficit/hyperactivity disorder (ADHD). Although the nature of this phenomenon is still unclear, it has been hypothesised to reflect interference from the Default Mode Network (DMN). So far, ISV-RT has been operationally defined either as a frequency spectrum of the underlying RT time series, or as a measure of dispersion of the RT scores distribution. Here, we use a novel RT analysis framework to link these hitherto unconnected facets of ISV-RT by determining the sensitivity of different measures of RT dispersion to the frequency content of the underlying RT time series. N=27 patients with ADHD and N=26 healthy controls performed several visual N-back tasks. Different measures of RT dispersion were repeatedly modelled after individual frequency bands of the underlying RT time series had been either extracted or suppressed using frequency-domain filtering. We found that the intra-subject standard deviation of RT preserves the “1/f noise” characteristic typical of human RT data. Furthermore and most importantly, we found that the ex-Gaussian parameter τ is rather exclusively sensitive to frequencies below 0.025 Hz in the underlying RT time series and that the particularly slow RTs, which nourish τ, occur regularly as part of an quasi-periodic, ultra-slow RT fluctuation. Overall, our results are compatible with the idea that ISV-RT is modulated by an endogenous, slowly fluctuating process that may reflect DMN interference.

Fixation and saccade control in an express-saccade maker

In express-saccade makers a large incidence of express saccades (latencies around 100 ms) is paralleled by a reduced ability to suppress saccade generation when required. Such a behavior occurs frequently in dyslexies. We studied the latencies and the metrical properties of saccades in the very rare case of an adult, nondyslexic express-saccade maker (male, age 29 years). The subject produced 65–95% express saccades in the gap (fixation point removed 200 ms before target onset) as well as in the overlap (fixation point not removed) paradigm, which qualified the subject as the most clear case of an express-saccade maker found so far. The number of express saccades increased rather than decreased when fixation foreperiod, gap duration, and target location were randomized from trial to trial as compared to when they remained constant. In the memory-guided saccade and in the antisaccade paradigms in which immediate saccade execution to a visual target had to be suppressed, the subject often reacted to the target with express saccades in an involuntary way. The amplitudes of express saccades were — in some conditions — found to progressively decrease with increasing latency, giving rise to amplitude transition functions. The present findings disprove the notion that express saccades are generated based on the prediction of the time and location of target appearance and support the notion that they are the result of an optomotor reflex. It is argued that the operation of the reflex is gated by a separate fixation system. Express-saccade makers are described as subjects with a dysfunction of the fixation system. Recent neurophysiological findings suggest that the subject studied in the present study has a selective dysfunction of the fixation system at the level of the superior colliculus.

Increased reaction time variability in attention-deficit hyperactivity disorder as a response-related phenomenon: evidence from single-trial event-related potentials.

BACKGROUND Increased intra-subject variability (ISV) in reaction times (RTs) is a promising endophenotype for attention-deficit hyperactivity disorder (ADHD) and among the most robust hallmarks of the disorder. ISV has been assumed to represent an attentional deficit, either reflecting lapses in attention or increased neural noise. Here, we use an innovative single-trial event-related potential approach to assess whether the increased ISV associated with ADHD is indeed attributable to attention, or whether it is related to response-related processing. METHODS We measured electroencephalographic responses to working memory oddball tasks in patients with ADHD (N = 20, aged 11.3 ± 1.1) and healthy controls (N = 25, aged 11.7 ± 1.1), and analysed these data with a recently developed method of single-trial event-related potential analysis. Estimates of component latency variability were computed for the stimulus-locked and response-locked forms of the P3b and the lateralised readiness potential (LRP). RESULTS ADHD patients showed significantly increased ISV in behavioural ISV. This increased ISV was paralleled by an increase in variability in response-locked event-related potential latencies, while variability in stimulus-locked latencies was equivalent between groups. This result held across the P3b and LRP. Latency of all components predicted RTs on a single-trial basis, confirming that all were relevant for speed of processing. CONCLUSIONS These data suggest that the increased ISV found in ADHD could be associated with response-end, rather than stimulus-end processes, in contrast to prevailing conceptions about the endophenotype. This mental chronometric approach may also be useful for exploring whether the existing lack of specificity of ISV to particular psychiatric conditions can be improved upon.

No significant brain volume decreases or increases in adults with high-functioning autism spectrum disorder and above average intelligence: A voxel-based morphometric study

Autism spectrum disorder (ASD) is increasingly being recognized as an important issue in adult psychiatry and psychotherapy. High intelligence indicates overall good brain functioning and might thus present a particularly good opportunity to study possible cerebral correlates of core autistic features in terms of impaired social cognition, communication skills, the need for routines, and circumscribed interests. Anatomical MRI data sets for 30 highly intelligent patients with high-functioning autism and 30 pairwise-matched control subjects were acquired and analyzed with voxel-based morphometry. The gray matter volume of the pairwise-matched patients and the controls did not differ significantly. When correcting for total brain volume influences, the patients with ASD exhibited smaller left superior frontal volumes on a trend level. Heterogeneous volumetric findings in earlier studies might partly be explained by study samples biased by a high inclusion rate of secondary forms of ASD, which often go along with neuronal abnormalities. Including only patients with high IQ scores might have decreased the influence of secondary forms of ASD and might explain the absence of significant volumetric differences between the patients and the controls in this study.

COMT Val158Met genotype is associated with fluctuations in working memory performance: converging evidence from behavioural and single-trial P3b measures

Intra-subject variability in reaction times (ISV) is a promising endophenotype for several psychiatric conditions, but its neural underpinnings are not yet established. Converging evidence from neuroimaging, molecular genetics, and psychopharmacology suggests that ISV could index catecholaminergically-mediated neural noise. The fine-grained temporal resolution of electroencephalography is ideal for investigating ISV, but only if potential neural correlates of ISV can be assessed in single trials. Based on evidence that ISV is associated with dopaminergic functioning, we apply a recently developed method of single-trial P3b analysis to investigate the association of COMT Val(158)Met genotype with measures of ISV on the behavioural and neural levels at different working memory loads. Greater number of Met alleles was associated with poorer and more intra-individually variable performance on the tasks, and greater latency jitter in single-trial P3bs. These converging results at the behavioural and neurophysiological levels confirm previous observations that prefrontal dopamine availability is associated with stability and accuracy of cognitive performance. Together with previous studies, these data imply pleiotropic cognitive effects of COMT genotype.