ADHD subjects fail to suppress eye blinks and microsaccades while anticipating visual stimuli but recover with medication

MMoshe Fried, Eteri Tsitsiashvil Yoram S.Bonneh, Anna Sterkin, Tamara Wygnanski-Jaffe, Tamir Epstein, Uri Polat

Published in Vision Res 2014 aug 101:62-72

By Baruch Styr

The aim of the article is to explored the oculomotor markers of Attention deficit hyperactivity disorder (ADHD) that are involuntary and quantitative and that could be used to reveal the core-affected mechanisms, as well as be used for differential diagnosis
Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder with a genetic component (Guan et al ) ADHD affects 3-10% of children in the USA. Some 50% of them continue to suffer from this disorder throughout adulthood. A recent review concluded that ‘‘The substantial societal burden of adult ADHD highlights the importance of providing a better understanding of the factors that contribute to accurate diagnosis and of improving the low recognition of the disorder in many world regions’’ (Asherson et al., 2012).
Several computerized continuous performance tests (CPT) aim to provide better diagnostics of the disorder. The most used CPT is the T.O.V.A (Greenberg & Waldman 1993). However the reliability of the T.O.V.A, is still debated (Zelnik 2012).

In recent years there has been an attempt to find a reliable diagnostic tool based on physiological markers. One of them was the visual system (Martin et al. 2008: Poltavski 2012) with a potential interest in: pattern of microsaccades , and pupil dilatation.
Microsaccades, which are small saccades associated with visual fixation, have been recently linked with attention both in space( biasing microsaccade direction) (Laubrock et al ., 2010) and time (Pastukhov et al ., 2012). In response to perceptual events, microsaccades are typically inhibited for a duration that depends on the stimulus parameters and attention (Rolfs, 2009). Anticipated events are preceded by microsacaddes inhibition (Betta&Turatto, 2006) and reaction times are typically faster when microsacaddes are inhibited around stimulus onset (Kliegel et al,. 2009) Moreover, higher attentional load is associated with lower microsaccade rates (Pastukhov & Braun 2010), and attended as well as surprising stimuli induced prolonged inhibition. Microsaccades have not been well analyzed in ADHD patients so far. One study found that these patients have significantly more sacaddes (> 2) (Munoz et al ,.2003). The pattern of microsacaddic response to perceptual stimuli, as well as the ongoing modulation of microsaccades rate under attentional demands could potentially be used to characterize the variables of attention.

Blink rate has also been linked with mental states and attention. Blink rates were found to be negatively correlated with arousal (Tanaka 1999) and increase with prolonged wakefulness (Barbato et al, 2007) presumably due to reduction in inhibitory control.
Pupil diameter is also correlated with mental activities (Kahunman & Beatty, 1966) and reacts in response to changes of the balance between sympathetic and parasympathetic stimulation. Stimulants as MPH affect pupil diameter.

The aim of the study was to investigate a difference in these parameters between ADHD–diagnosed and control subjects, in a task that involves dynamic allocation of attention. An additional aim was to investigate the effect of medication on these parameters, especially weather it normalizes them as it normalizes behavior.

METHODS
22 adults subjects diagnosed with ADHD , 12 males , 10 females. Age 33.9 +- 13.1
Controls 22 subjects . Age 31.4 +- 8.5

MEDICATION
All the subjects were under medication with MPH . With their usual effective doses.

STIMULUS & PROCEDURE
The session consisted of a sequence of 648 T.O.V.A trials of stimuli of 100ms each.

TRACKING EYE MOVEMENTS
Eye movements were recorded with EyeLink ® 1000 desktop model from SR-Rsearch.

RESULTS
Results showed the unmedicated ADHD group differed from the control group, showing reduced suppression of sacaddes and blinks when they had to be suppressed, and recovery from these abnormalities with medication. Blink Rate: The control group showed no blinks in the interval prior during and shortly after the presentation of the stimulus. The medicated ADHD subjects showed a high rate of blinks.
There was no difference in blink rates between the medicated ADHD group and the controls.

MICROSACADDE RATE

The unmediated ADHD group showed much more microsacaddes through the T.O.V.A session than the control group. The higher average rate was reduced to the average control rate with medication ( p<0.0001). DISCUSSION
Looking for oculomotor markers related to the core deficit of ADHD that could contribute to a more objective and reliable diagnosis. The tree groups of subjects: control, unmedicated ADHD and medicated ADHD were compared. The results show that ADHD unmedicated subjects have significantly higher rates of eye blinks and microsaccades compared with the control group. This effect is largest in the peri-stimulus interval. With medication a striking effect of normalization was found, with full normalization of micrisacaddes rate in relation to the control level, and partial normalization of blink rates mainly in the peri-stimulus interval.

CONCLUSIONS
The study examined the ocular parameters of adults with ADHD undergoing a T.O.V.A CPT test, and found differences between controls unmedicated and medicated ADHD subjects. The ocular measurements examined are largely involuntary and therefore could potentially serve as an objective physiological marker for diagnosing ADHD.

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