Unique Patterns of Eye Movements Characterizing Inattentive Reading in ADHD.

OBJECTIVE: We aimed to identify unique patterns of eye-movements measures reflecting inattentive reading among adults with and without ADHD. METHOD & RESULTS: We recorded eye-movements during uninterrupted text reading of typically developed (TD) and ADHD adults. First, we found significantly longer reading time for the ADHD group than the TD group. Further, we detected cases in which words were reread more than twice and found that such occasions were much more frequent in participants with ADHD than in TD participants. Moreover, we discovered that the first reading pass of these words was less sensitive to the length of the word than the first pass of words read only once, indicating a less meaningful reading. CONCLUSION: We propose that high rate of words that were reread is a correlate of inattentive reading which is more pronounced among ADHD readers. Implications of the findings in the context of reading comprehension are discussed.

Rhythmic attentional sampling in autism.

Individuals diagnosed with autism often display alterations in visual spatial attention toward visual stimuli, but the underlying cause of these differences remains unclear. Recent evidence has demonstrated that covert spatial attention, rather than remaining constant at a cued location, samples stimuli rhythmically at a frequency of 4-8 Hz (theta). Here we tested whether rhythmic sampling of attention is altered in autism. Participants were asked to monitor three locations to detect a brief target presented 300-1200 ms after a spatial cue. Visual attention was oriented to the cue and modified visual processing at the cued location, consistent with previous studies. We measured detection performance at different cue-target intervals when the target occurred at the cued location. Significant oscillations in detection performance were identified using both a traditional time-shuffled approach and a new autoregressive surrogate method developed by Brookshire in 2022. We found that attention enhances behavioral performance rhythmically at the same frequency in both autism and control group at the cued location. However, rhythmic temporal structure was not observed in a subgroup of autistic individuals with co-occurring attention-deficit/hyperactivity disorder (ADHD). Our results imply that intrinsic brain rhythms which organize neural activity into alternating attentional states is functional in autistic individuals, but may be altered in autistic participants who have a concurrent ADHD diagnosis.

Cortical Surface Area Relates to Distinct Computational Properties in Human Visual Perception.

Understanding the relationship between cortical structure and function is essential for elucidating the neural basis of human behavior. However, the impact of cortical structural features on the computational properties of neural circuits remains poorly understood. In this study, we demonstrate that a simple structural feature - cortical surface area (SA) - relates to specific computational properties underlying human visual perception. By combining psychophysical, neuroimaging, and computational modeling approaches, we show that differences in SA in the parietal and frontal cortices are associated with distinct patterns of behavior in a motion perception task. These behavioral differences can be accounted for by specific parameters of a divisive normalization model, suggesting that SA in these regions contributes uniquely to the spatial organization of cortical circuitry. Our findings provide novel evidence linking cortical structure to distinct computational properties and offer a framework for understanding how cortical architecture can impact human behavior.

Near and Far Transfer Effects of Computerized Progressive Attention Training (CPAT) Versus Mindfulness Based Stress Reduction (MBSR) Practice Among Adults With ADHD.

OBJECTIVE: The present study evaluated the near (attention) and far (reading, ADHD symptoms, learning, and quality of life) transfer effects of a Computerized Progressive Attention Training (CPAT) versus Mindfulness Based Stress Reduction (MBSR) practice among adults with ADHD compared to a passive group. METHOD: Fifty-four adults participated in a non-fully randomized controlled trial. Participants in the intervention groups completed eight 2-hr weekly training sessions. Outcomes were assessed before, immediately after, and 4 months post-intervention, using objective tools: attention tests, eye-tracker, and subjective questionnaires. RESULTS: Both interventions showed near-transfer to various attention functions. The CPAT produced far-transfer effects to reading, ADHD symptoms, and learning while the MBSR improved the self-perceived quality of life. At follow-up, all improvements except for ADHD symptoms were preserved in the CPAT group. The MBSR group showed mixed preservations. CONCLUSION: Both interventions have beneficial effects, however only the CPAT group exhibited improvements compared to the passive group.

Are attention and cognitive control altered by fMRI scanner environment? Evidence from Go/No-go tasks in ADHD.

It is widely assumed that cognitive processes studied in fMRI are equivalent to cognitive processes engaged in the same experimental paradigms in typical behavioral lab settings. Yet very few studies examined this common assumption, and the results have been equivocal. In the current study we directly tested the effects of fMRI environment on sustained attention and response inhibition, using a Go/No-go task, among participants with (n = 42) and without (n = 21) attention deficit/hyperactivity disorder (ADHD). Participants with ADHD are characterized by deficits in these cognitive functions and may be particularly susceptible to environmental effects on attention. We found a substantial slowing of reaction time in the scanner for all participants, and a trend for enhanced sustained attention, particularly in ADHD participants with poor performance. We also report limited stability of individual differences in scores obtained in the lab and in the scanner. These findings call for cautious interpretation of neuroimaging task-related results, especially those obtained in clinical populations.

Late fMRI Response Components Are Altered in Autism Spectrum Disorder.

Disrupted cortical neural inhibition has been hypothesized to be a primary contributor to the pathophysiology of autism spectrum disorder (ASD). This hypothesis predicts that ASD will be associated with an increase in neural responses. We tested this prediction by comparing fMRI response magnitudes to simultaneous visual, auditory, and motor stimulation in ASD and neurotypical (NT) individuals. No increases in the initial transient response in any brain region were observed in ASD, suggesting that there is no increase in overall cortical neural excitability. Most notably, there were widespread fMRI magnitude increases in the ASD response following stimulation offset, approximately 6-8 s after the termination of sensory and motor stimulation. In some regions, the higher fMRI offset response in ASD could be attributed to a lack of an "undershoot"-an often observed feature of fMRI responses believed to reflect inhibitory processing. Offset response magnitude was associated with reaction times (RT) in the NT group and may explain an overall reduced RT in the ASD group. Overall, our results suggest that increases in neural responsiveness are present in ASD but are confined to specific components of the neural response, are particularly strong following stimulation offset, and are linked to differences in RT.

Weaker neural suppression in autism.

Abnormal sensory processing has been observed in autism, including superior visual motion discrimination, but the neural basis for these sensory changes remains unknown. Leveraging well-characterized suppressive neural circuits in the visual system, we used behavioral and fMRI tasks to demonstrate a significant reduction in neural suppression in young adults with autism spectrum disorder (ASD) compared to neurotypical controls. MR spectroscopy measurements revealed no group differences in neurotransmitter signals. We show how a computational model that incorporates divisive normalization, as well as narrower top-down gain (that could result, for example, from a narrower window of attention), can explain our observations and divergent previous findings. Thus, weaker neural suppression is reflected in visual task performance and fMRI measures in ASD, and may be attributable to differences in top-down processing.

Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder.

The balance of excitation and inhibition in neural circuits is hypothesized to be increased in autism spectrum disorder, possibly mediated by altered signaling of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), yet empirical evidence in humans is inconsistent. We used edited magnetic resonance spectroscopy (MRS) to quantify signals associated with both GABA and the excitatory neurotransmitter glutamate in multiple regions of the sensory and sensorimotor cortex, including primary visual, auditory, and motor areas in adult individuals with autism and in neurotypical controls. Despite the strong a priori hypothesis of reduced GABA in autism spectrum disorder, we found no group differences in neurometabolite concentrations in any of the examined regions and no correlations of MRS measure with psychophysical visual sensitivity or autism symptomatology. We demonstrate high data quality that is comparable across groups, with a relatively large sample of well-characterized participants, and use Bayesian statistics to corroborate the lack of any group differences. We conclude that levels of GABA and Glx (glutamate, glutamine, and glutathione) in the sensory and sensorimotor cortex, as measured with MRS at 3T, are comparable in adults with autism and neurotypical individuals. Autism Res 2020, 13: 1111-1129. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: γ-Aminobutyric acid (GABA) and glutamate are the main inhibitory and excitatory neurotransmitters in the human brain, respectively, and their balanced interaction is necessary for neural function. Previous research suggests that the GABA and glutamate systems might be altered in autism. In this study, we used magnetic resonance spectroscopy to measure concentrations of these neurotransmitters in the sensory areas in the brains of young adults with autism. In contradiction to the common hypothesis of reduced GABA in autism, we demonstrate that concentrations of both GABA and glutamate, in all the brain regions examined, are comparable in individuals with autism and in neurotypical adults. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Response Dissociation in Hierarchical Cortical Circuits: a Unique Feature of Autism Spectrum Disorder.

A prominent hypothesis regarding the pathophysiology of autism is that an increase in the balance between neural excitation and inhibition results in an increase in neural responses. However, previous reports of population-level response magnitude in individuals with autism have been inconsistent. Critically, network interactions have not been considered in previous neuroimaging studies of excitation and inhibition imbalance in autism. In particular, a defining characteristic of cortical organization is its hierarchical and interactive structure; sensory and cognitive systems are comprised of networks where later stages inherit and build upon the processing of earlier input stages, and also influence and shape earlier stages by top-down modulation. Here we used the well established connections of the human visual system to examine response magnitudes in a higher-order motion processing region [middle temporal area (MT+)] and its primary input region (V1). Simple visual stimuli were presented to adult individuals with autism spectrum disorders (ASD; n = 24, mean age 23 years, 8 females) and neurotypical controls (n = 24, mean age 22, 8 females) during fMRI scanning. We discovered a strong dissociation of fMRI response magnitude between region MT+ and V1 in individuals with ASD: individuals with high MT+ responses had attenuated V1 responses. The magnitude of MT+ amplification and of V1 attenuation was associated with autism severity, appeared to result from amplified suppressive feedback from MT+ to V1, and was not present in neurotypical controls. Our results reveal the potential role of altered hierarchical network interactions in the pathophysiology of ASD.SIGNIFICANCE STATEMENT An imbalance between neural excitation and inhibition, resulting in increased neural responses, has been suggested as a pathophysiological pathway to autism, but direct evidence from humans is lacking. In the current study we consider the role of interactions between stages of sensory processing when testing increased neural responses in individuals with autism. We used the well known hierarchical structure of the visual motion pathway to demonstrate dissociation in the fMRI response magnitude between adjacent stages of processing in autism: responses are attenuated in a primary visual area but amplified in a subsequent higher-order area. This response dissociation appears to rely on enhanced suppressive feedback between regions and reveals a previously unknown cortical network alteration in autism.

Fronto-parietal engagement in response inhibition is inversely scaled with attention-deficit/hyperactivity disorder symptom severity.

BACKGROUND: Impaired response inhibition is one of the most consistent findings in attention deficit hyperactivity disorder (ADHD). However, the underlying brain mechanisms are not clear. This study aimed to underpin atypical inhibition-related brain activation and connectivity patterns in ADHD using a novel Go/No-go task design, and to determine its association with clinical symptoms of the disorder. METHODS: Forty-eight adults with ADHD performed a Go/No-go task in which target frequency was manipulated during functional MRI. Specific inhibition-related brain activation was correlated with ADHD symptom severity, to assess the relationship of individual differences in engagement of inhibition-related brain circuits with the magnitude of every-day functioning impairments. Finally, generalized psychophysical interaction analyses were carried out to examine whether not only engagement but also functional connectivity between regions implicated in response inhibition is related to symptom severity. RESULTS: We found no evidence for the expected parietal modulation by increased demand for inhibition at the group-level results. However, this lack of modulation was mediated by individual differences in ADHD symptom severity - increased engagement of the intraparietal sulcus (IPS) in inhibition-demanding events was evident in individuals with less severe symptoms but dissipated with increase in symptomatology. Similarly, functional connectivity between the IPS and the right inferior frontal gyrus (rIFG) was elevated under high inhibitory demand conditions, but this effect diminished with increased symptom severity. CONCLUSIONS: The results highlight the importance of IPS engagement in response inhibition and suggest that IPS modulation may be driven by top-down control from the IFG. Moreover, the current findings force the point of treating ADHD as a continuum whereby brain correlates are scaled with severity of the disorder, and point to the potential use of individual differences in the modulation of IPS activation and connectivity as a neuromarker of ADHD.

Glutamatergic facilitation of neural responses in MT enhances motion perception in humans.

There is large individual variability in human neural responses and perceptual abilities. The factors that give rise to these individual differences, however, remain largely unknown. To examine these factors, we measured fMRI responses to moving gratings in the motion-selective region MT, and perceptual duration thresholds for motion direction discrimination. Further, we acquired MR spectroscopy data, which allowed us to quantify an index of neurotransmitter levels in the region of area MT. These three measurements were conducted in separate experimental sessions within the same group of male and female subjects. We show that stronger Glx (glutamate + glutamine) signals in the MT region are associated with both higher fMRI responses and superior psychophysical task performance. Our results suggest that greater baseline levels of glutamate within MT facilitate motion perception by increasing neural responses in this region.

Reduced auditory cortical adaptation in autism spectrum disorder.

Adaptation is a fundamental property of cortical neurons and has been suggested to be altered in individuals with autism spectrum disorder (ASD). We used fMRI to measure adaptation induced by repeated audio-visual stimulation in early sensory cortical areas in individuals with ASD and neurotypical (NT) controls. The initial transient responses were equivalent between groups in both visual and auditory cortices and when stimulation occurred with fixed-interval and randomized-interval timing. However, in auditory but not visual cortex, the post-transient sustained response was greater in individuals with ASD than NT controls in the fixed-interval timing condition, reflecting reduced adaptation. Further, individual differences in the sustained response in auditory cortex correlated with ASD symptom severity. These findings are consistent with hypotheses that ASD is associated with increased neural responsiveness but that responsiveness differences only manifest after repeated stimulation, are specific to the temporal pattern of stimulation, and are confined to specific cortical regions.

Sex Differences in Visual Motion Processing.

The importance of sex as a biological variable has recently been emphasized by major funding organizations [1] and within the neuroscience community [2]. Critical sex-based neural differences are indicated by, for example, conditions such as autism spectrum disorder (ASD) that have a strong sex bias with a higher prevalence among males [51, 3]. Motivated by this broader context, we report a marked sex difference in a visual motion perception task among neurotypical adults. Motion duration thresholds [4, 5]-the minimum duration needed to accurately perceive motion direction-were considerably shorter for males than females. We replicated this result across three laboratories and 263 total participants. This type of enhanced performance has previously been observed only in special populations including ASD, depression, and senescence [6-8]. The observed sex difference cannot be explained by general differences in speed of visual processing, overall visual discrimination abilities, or potential motor-related differences. We also show that while individual differences in motion duration thresholds are associated with differences in fMRI responsiveness of human MT+, surprisingly, MT+ response magnitudes did not differ between males and females. Thus, we reason that sex differences in motion perception are not captured by an MT+ fMRI measure that predicts within-sex individual differences in perception. Overall, these results show how sex differences can manifest unexpectedly, highlighting the importance of sex as a factor in the design and analysis of perceptual and cognitive studies.

Isolating response inhibition in the brain: Parietal versus frontal contribution.

Response inhibition is a main function of cognitive control and its neural substrates have been studied extensively. However, it is still a question whether previous brain imaging investigations were successful in isolating specific response inhibition activation. In the current study we attempted to pinpoint response inhibition in the brain using a Go/No-go task and fMRI, by contrasting rare-No-go trials with prevalent-No-go trials. Although inhibition is required in all No-go trials, task variants with rare-No-go cases (25%) create a prepotent response which elicits a strong demand for inhibition, while task variants with prevalent-No-go cases (75%) require very little inhibition effort. Since the neural activation in this design is extracted solely from No-go trials, differing only in the extent of inhibitory demand, the analysis avoids contamination of the data with motor effects or visual factors. Using this experimental design we highlight the contribution of the parietal cortex (bilaterally) to inhibitory processes, while casting doubts about the specificity of frontal activation in such processes. Future studies are required to verify that bilateral intraparietal sulcus and left temporo-parietal junction activations could be markers of inhibitory control.

Attention Functioning Among Adolescents With Multiple Learning, Attentional, Behavioral, and Emotional Difficulties.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by high levels of inattention, hyperactivity, and impulsivity; however, these symptoms can result from a variety of reasons. To obtain a comprehensive understanding of the various difficulties of individuals with ADHD, especially when co-occurrence difficulties are present, it is essential to combine neuropsychological and subjective assessment tools. In the present field study the authors investigated a group of adolescents with multiple deficits (MD) using neuropsychological and subjective measures. Teachers' ratings verified extremely high levels of symptoms of oppositional behavior, inattention, hyperactivity-impulsivity, social problems, and emotional problems in this group. As expected, MD group participants showed decreased abilities to maintain attention on task for a long period of time, focus attention and effectively inhibit adjacent distractors, and resist conflicting irrelevant information. Importantly, although significant differences in the attention measures were observed at the group level, not all MD participants displayed deviant performance. Thus, we conclude that the heterogeneous group of adolescents with MD comprises individuals with primary attention deficits as well as those with other nonattentional deficits that show equivalent behavioral symptoms. Using neuropsychological tools can be useful in differentiating between different core deficits and in guiding appropriate interventions.