Christine M. Falter

Timing deficits in attention-deficit/hyperactivity disorder (ADHD) : Evidence from neurocognitive and neuroimaging studies

Relatively recently, neurocognitive and neuroimaging studies have indicated that individuals with attention-deficit/hyperactivity disorder (ADHD) may have deficits in a range of timing functions and their underlying neural networks. Despite this evidence, timing deficits in ADHD are still somewhat neglected in the literature and mostly omitted from reviews on ADHD. There is therefore a lack of integrative reviews on the up-to-date evidence on neurocognitive and neurofunctional deficits of timing in ADHD and their significance with respect to other behavioural and cognitive deficits. The present review provides a synthetic overview of the evidence for neurocognitive and neurofunctional deficits in ADHD in timing functions, and integrates this evidence with the cognitive neuroscience literature of the neural substrates of timing. The review demonstrates that ADHD patients are consistently impaired in three major timing domains, in motor timing, perceptual timing and temporal foresight, comprising several timeframes spanning milliseconds, seconds, minutes and longer intervals up to years. The most consistent impairments in ADHD are found in sensorimotor synchronisation, duration discrimination, reproduction and delay discounting. These neurocognitive findings of timing deficits in ADHD are furthermore supported by functional neuroimaging studies that show dysfunctions in the key inferior fronto-striato-cerebellar and fronto-parietal networks that mediate the timing functions. Although there is evidence that these timing functions are inter-correlated with other executive functions that are well established to be impaired in the disorder, in particular working memory, attention, and to a lesser degree inhibitory control, the key timing deficits appear to survive when these functions are controlled for, suggesting independent cognitive deficits in the temporal domain. There is furthermore strong evidence for an association between timing deficits and behavioural measures of impulsiveness and inattention, suggesting that timing problems are key to the clinical behavioural profile of ADHD. Emerging evidence shows that the most common treatment of ADHD with the dopamine agonist and psychostimulant Methylphenidate attenuates most timing deficits in ADHD and normalises the abnormally blunted recruitment of the underlying fronto-striato-cerebellar networks. Timing function deficits in ADHD, therefore, next to executive function deficits, form an independent impairment domain, and should receive more attention in neuropsychological, neuroimaging, and pharmacological basic research as well as in translational research aimed to develop pharmacological or non-pharmacological treatment of abnormal timing behaviour and cognition in ADHD.

More consistent, yet less sensitive: interval timing in autism spectrum disorders.

Even though phenomenological observations and anecdotal reports suggest atypical time processing in individuals with an autism spectrum disorder (ASD), very few psychophysical studies have investigated interval timing, and the obtained results are contradictory. The present study aimed to clarify which timing processes function atypically in ASD and whether they are related to the ASD diagnostic profile. Visual, auditory, and cross-modal interval timing was assessed in 18 individuals with ASD using a repeated standards version of the temporal generalization task. The use of two different standard durations (600 and 1,000 ms) allowed for an assessment of the scalar property of interval timing in ASD, a fundamental characteristic of interval timing. The ASD group showed clearer adherence to the scalar property of interval timing than the control group. In addition, both groups showed the normal effect that auditory stimuli had longer subjective durations than visual ones. Yet, signal detection analysis showed that the sensitivity of temporal discrimination was reduced in the ASD group across modalities, in particular for auditory standards. Moreover, response criteria in the ASD group were related to symptom strength in the communication domain. The findings suggest that temporal intervals are fundamentally processed in the same way in ASD and TD, but with reduced sensitivity for temporal interval differences in ASD. Individuals with ASD may show a more conservative response strategy due to generally decreased sensitivity for the perception of time intervals.

Enhanced Visual Temporal Resolution in Autism Spectrum Disorders

Cognitive functions that rely on accurate sequencing of events, such as action planning and execution, verbal and nonverbal communication, and social interaction rely on well-tuned coding of temporal event-structure. Visual temporal event-structure coding was tested in 17 high-functioning adolescents and adults with autism spectrum disorder (ASD) and mental- and chronological-age matched typically-developing (TD) individuals using a perceptual simultaneity paradigm. Visual simultaneity thresholds were lower in individuals with ASD compared to TD individuals, suggesting that autism may be characterised by increased parsing of temporal event-structure, with a decreased capability for integration over time. Lower perceptual simultaneity thresholds in ASD were also related to increased developmental communication difficulties. These results are linked to detail-focussed and local processing bias.

Interval timing deficits and abnormal cognitive development

mance even for relatively small sample sizes (Szelag et al., 2004). Thus, in spite of the lack of universality of interval timing defi-cits, the increased incidence rate needs to be explained. Moreover, it has been suggested that ADHD and ASD share some suscep-tibility genes (Castellanos and Tannock, 2002), which makes it likely that some dysfunctions are shared between them or their subtypes. We propose that the focus of research needs to be on the association of interval timing abnormalities and other functional deficits. For instance, although a Theory of Mind deficit can hamper the understanding of social situations in its own right, an additional interval timing deficit could result in a lack of precise perception of temporal cues of eye gaze, and thereby increase misinterpretations of social situ-ations. It has been proposed that different symptoms can be independent dimensions of impairment, which nevertheless interact with and modulate one another, leading to the characteristic phenomenology of an individual with a developmental disorder (Happe et al., 2006). In this line of thought, interval timing abnormalities might inter-act with primary dysfunctions.In fact, several ADHD studies confirmed significant associations between duration perception and other cognitive functions. Toplak and Tannock (2005) reported sig-nificant correlations between time discrim-ination thresholds and working memory measures in participants with ADHD, but not in healthy individuals. Rubia and col-leagues argued persuasively that the pri-mary ADHD symptom of impulsiveness is based on poor inhibition and attention functions, as well as on poor interval tim-ing (Rubia, 2002; Rubia et al., 2009). Even though interaction between interval tim-ing and other cognitive functions is much less investigated in ASD than in ADHD, preliminary findings show significant correlation between timing measures in a temporal bisection task and primary ASD symptoms in the language and com-munication domain (Allman et al., 2011). option would be that abnormal interval timing could be an epiphenomenon of developmental disorders without bearing a causal relationship to other symptoms.The idea of an ontogenetic causal relation-ship raises the question of why the phenom-enological outcomes of the disorders differ so strongly. The apparent lack of specificity of interval timing deficits to ASD and ADHD raises the question of their explanatory rel-evance for the ontogenesis of a particular developmental disorder. A further challenge for the causality assumption is the lack of uni-versality of interval timing abnormalities. A few studies report null findings ( Wallace and Happe, 2008; Jones et al., 2009), and in studies showing group differences not all individu-als with ASD or ADHD perform atypically. Indeed, the range of reproduced time inter-vals can be quite variable and the variability is often increased in ASD and ADHD compared to typically developing controls ( Toplak et al., 2003; Martin et al., 2010). At the current stage of knowledge, therefore, it seems premature to suggest that interval timing abnormalities can be the sole ontogenetic cause of ASD or ADHD.Nevertheless, before we discard any causal account in favor of the alternative view of interval timing as a mere epiphe-nomenon of atypical cognitive develop-ment, we suggest that a more associative view of the role of interval timing in cog-nitive development be adopted. Indeed, there is strong evidence for the association between temporal processing and other typical cognitive functions such as social cognition (Trevarthen and Daniel, 2005; Striano et al., 2006), language processing (Tallal et al., 1993), and understanding of causality (Freeman, 2008). Therefore, it is difficult to conceive how an impairment of interval timing would have no relevance for developmental disorders, which show deficits in cognitive functions relying on accurate timing. Furthermore, the inci-dence of interval timing abnormalities is increased in developmental disorders, as shown by group differences in perfor-Time perception deficits represent an aspect of cognitive malfunctioning shared by developmental disorders, which otherwise seem distinct with respect to their individual primary symptom clusters, such as autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). Multiple impairments of social interaction, communication, and restricted interests constitute the diagnostic criteria for ASD, whereas behavioral symptoms of ADHD comprise inattention, hyperactivity, and impulsivity (DSM-IV-TR; American Psychiatric Association, 2000). Both ASD and ADHD are additionally associated with non-diagnostic secondary symptoms in perception and cognition. A secondary symptom observed in both ASD and ADHD is abnormal interval timing, i.e., processing of stimulus duration (for a review see Falter and Noreika, accepted). For instance, it has been reported that reproduction of auditory and visual intervals of 1–5.5 s was impaired in individuals with ASD (Szelag et al., 2004). Similarly, Barkley etal. (2001) found that individuals with ADHD were impaired in reproducing intervals of 2–60 s.It is difficult to assess whether secondary symptoms in general and interval timing abnormalities in particular play a causal role in developmental disorders. There are several possible relationships. First, a direct causal relationship would characterize a case in which impairment of an interval timing system could directly disrupt (otherwise possibly unimpaired) cognitive functions relying on accurate timing information, resulting in the known primary symptoms. Although such a direct causal relationship might be found in adult neuropsychology, it is not applicable to the study of devel-opmental disorders, which are characterized by atypical neurogenetic pathways of cognitive development. Rather, as a second option, an ontogenetic causal relationship is conceivable in which an impaired interval timing system could affect the development of all processes downstream, which rely on accurate timing information. Finally, a third

Object-based attention benefits reveal selective abnormalities of visual integration in autism.

A pervasive integration deficit could provide a powerful and elegant account of cognitive processing in autism spectrum disorders (ASD). However, in the case of visual Gestalt grouping, typically assessed by tasks that require participants explicitly to introspect on their own grouping perception, clear evidence for such a deficit remains elusive. To resolve this issue, we adopt an index of Gestalt grouping from the object‐based attention literature that does not require participants to assess their own grouping perception. Children with ASD and mental‐ and chronological‐age matched typically developing children (TD) performed speeded orientation discriminations of two diagonal lines. The lines were superimposed on circles that were either grouped together or segmented on the basis of color, proximity or these two dimensions in competition. The magnitude of performance benefits evident for grouped circles, relative to ungrouped circles, provided an index of grouping under various conditions. Children with ASD showed comparable grouping by proximity to the TD group, but reduced grouping by similarity. ASD seems characterized by a selective bias away from grouping by similarity combined with typical levels of grouping by proximity, rather than by a pervasive integration deficit.

Interaction of bottom-up and top-down processes in the perception of ambiguous figures.

Ambiguous figures reverse their appearance during prolonged viewing and can be perceived in two (or more) available interpretations. Both physical stimulus manipulations and cognitive control influence the perception of ambiguous figures, but the underlying mechanisms remain poorly understood. In the current study, the perception of an ambiguous figure was manipulated by adaptation to unambiguous figures and/or placing the ambiguous figure into a context of unambiguous figures. Our results indicate that both adaptation and context can effectively modulate perception of the ambiguous figure. When manipulated together, adaptation and context processes showed additive effects upon the perception of the ambiguous figure implying the independent mechanisms. Thus, top-down and bottom-up processes seem to influence the perception of the ambiguous figures independently and neither seems to be uniquely responsible for the generation of perceptual changes.

Sex Differences in Mental Rotation and How They Add to the Understanding of Autism

The most consistent cognitive sex differences have been found in the visuo-spatial domain, using Mental Rotation (MR) tasks. Such sex differences have been suggested to bear implications on our understanding of autism spectrum disorders (ASD). However, it is still debated how the sex difference in MR performance relates to differences between individuals with ASD compared to typically developed control persons (TD). To provide a detailed exploration of sex differences in MR performance, we studied rotational (indicated by slopes) and non-rotational aspects (indicated by intercepts) of the MR task in TD individuals (total N = 50). Second-to-fourth digit length ratios (2D:4D) were measured to investigate the associations between prenatal testosterone and performance on MR tasks. Handedness was assessed by the use of the Edinburgh Handedness Inventory in order to examine the relation between handedness and MR performance. In addition, we investigated the relation of spatial to systemising abilities, both of which have been associated with sex differences and with ASD, employing the Intuitive Physics Test (IPT). Results showed a male advantage in rotational aspects of the MR task, which correlated with IPT results. These findings are in contrast to the MR performance of individuals with ASD who have been shown to outperform TD persons in the non-rotational aspects of the MR task. These results suggest that the differences in MR performance due to ASD are different from sex-related differences in TD persons, in other words, ASD is not a simple and continuous extension of the male cognitive profile into the psychopathological range as the extreme male brain hypothesis (EMB) of ASD would suggest.

Perception of short time scale intervals in a hypnotic virtuoso.

Abstract Previous studies showed that hypnotized individuals underestimate temporal intervals in the range of several seconds to tens of minutes. However, no previous work has investigated whether duration perception is equally disorderly when shorter time intervals are probed. In this study, duration perception of a hypnotic virtuoso was tested using repeated standard temporal generalization and duration estimation tasks. When compared to the baseline state, hypnosis affected perception of intervals spread around 600 ms in the temporal generalization task but did not alter perception of slightly longer intervals spread around 1000 ms. Furthermore, generalization of temporal intervals was more orderly under hypnosis than in the baseline state. In contrast, the hypnotic virtuoso showed a typical time underestimation effect when perception of longer supra-second intervals was tested in the duration estimation task, replicating results of the previous hypnosis studies.

Perception of mirror symmetry in autism spectrum disorders

Gestalt grouping in autism spectrum disorders (ASD) is selectively impaired for certain organization principles but for not others. Symmetry is a fundamental Gestalt principle characterizing many biological shapes. Sensitivity to symmetry was tested using the Picture Symmetry Test, which requires finding symmetry lines on pictures. Individuals with ASD showed decreased sensitivity to symmetry and a correlation of test performance with performance IQ. Decreased sensitivity for symmetry in ASD is discussed in relation to reduced visual experience of faces in early development.

Bandpass characteristics of high-frequency sensitivity and visual experience in blindsight

Patient RP suffers a unilateral right homonymous quadrant anopia but demonstrates better than chance discrimination for stimuli presented in the blind field at temporal frequencies between 33 and 47Hz (all significant at p<.05, binomial). Examination of her reports of visual experience during blind-field discrimination suggests a more complex picture in which experiences particular to correct discrimination are not found at low-mid-gamma frequencies, but are significantly more likely than average (76%, p<.001) at a lower frequency (22Hz) at which blindsight is not observed. We believe that visual experience may serve to support blindsight if discrimination tasks are generally impaired at frequencies outside of the low-mid-gamma band. If this is so, although generally experienced as non-specific and unstructured light, the visual experience that accompanies discrimination performance must be based upon a neural representation which includes information on the visual features present in the stimulus.