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author:("zeidel, Eran")
1.  Atypical Neural Networks for Social Orienting in Autism Spectrum Disorders 
NeuroImage  2011;56(1):354-362.
Autism spectrum disorders (ASD) are characterized by significant social impairments, including deficits in orienting attention following social cues. Behavioral studies investigating social orienting in ASD, however, have yielded mixed results, as the use of naturalistic paradigms typically reveals clear deficits whereas computerized laboratory experiments often report normative behavior. The present study is the first to examine the neural mechanisms underlying social orienting in ASD in order to provide new insight into the social attention impairments that characterize this disorder. Using fMRI, we examined the neural correlates of social orienting in children and adolescents with ASD and in a matched sample of typically developing (TD) controls while they performed a spatial cueing paradigm with social (eye gaze) and nonsocial (arrow) cues. Cues were either directional (indicating left or right) or neutral (indicating no direction), and directional cues were uninformative of the upcoming target location in order to engage automatic processes by minimizing expectations. Behavioral results demonstrated intact orienting effects for social and nonsocial cues, with no differences between groups. The imaging results, however, revealed clear group differences in brain activity. When attention was directed by social cues compared to nonsocial cues, the TD group showed increased activity in frontoparietal attention networks, visual processing regions, and the striatum, whereas the ASD group only showed increased activity in the superior parietal lobule. Significant group × cue type interactions confirmed greater responsivity in task-relevant networks for social cues than nonsocial cues in TD as compared to ASD, despite similar behavioral performance. These results indicate that, in the autistic brain, social cues are not assigned the same privileged status as they are in the typically developing brain. These findings provide the first empirical evidence that the neural circuitry involved in social orienting is disrupted in ASD and highlight that normative behavioral performance in a laboratory setting may reflect compensatory mechanisms rather than intact social attention.
doi:10.1016/j.neuroimage.2011.02.031
PMCID: PMC3091391  PMID: 21334443
autism; attention; functional magnetic resonance imaging; gaze; social cue
2.  Rethinking a Right Hemisphere Deficit in ADHD 1 
Introduction
Early observations from lesion studies suggested right hemisphere (RH) dysfunction in ADHD. However, a strictly right-lateralized deficit has not been well supported. An alternatively view suggests increased R>L asymmetry of brain function and abnormal interhemispehric interaction. If true, RH pathology in ADHD should reflect interhemispherically networked and over-activated functioning. We evaluated these assertions.
Methods
Four elements of lateralized brain function were measured: LH specialized, RH specialized, LH with interhemispheric processing (LH/IH), and RH with interhemispheric processing (RH/IH). Next, we tested their association with cognitive ability, psychiatric comorbidity, and sibling correlations in 79 children with ADHD.
Results
RH/IH processing was uniquely associated with other outcome measures. There were no associations for independent RH or LH function alone.
Conclusions
Interhemispherically networked RH processing is critical in ADHD. Additionally, lack of association between LH specialized processing and cognitive ability (especially for verbal cognitive tasks) supports increased RH mediation of task processing.
doi:10.1177/1087054708323005
PMCID: PMC2834536  PMID: 18753404
3.  The Role of Task History in Simple Reaction Time to Lateralized Light Flashes 
Neuropsychologia  2007;46(2):659-664.
In lateralized simple reaction time (SRT) tasks with unimanual responses, reaction times (RTs) are faster with ipsilateral (uncrossed) than with contralateral (crossed) response hand- target hemifield combinations. The difference between crossed and uncrossed responses (CUD) is typically interpreted to reflect callosal transfer time. Indeed, split brain patients have much longer CUDs than control subjects. However, while many studies have supported the hypothesis that the CUD reflects callosal transmission time, a few studies have suggested that the CUD may be affected by non-anatomical factors. We investigated the nature of these inconsistent results in two experiments. In the first, we asked half of our subjects to cross their arms while performing the task. The CUD was not affected by arms crossing, supporting the anatomical model of the CUD. In the second experiment, however, all subjects were asked to cross their arms in half of the trials. In this experiment, arms crossing significantly affected the CUD, thus showing that spatial attention modulates the CUD. These latter results cannot be readily explained by a simple callosal relay interpretation of the CUD. Rather, the CUD seems to reflect a mix of anatomical and non-anatomical factors produced by task history. Thus, the seemingly inconsistent results of previous studies can be reconciled by taking into account differences in task history across studies.
doi:10.1016/j.neuropsychologia.2007.09.008
PMCID: PMC2426952  PMID: 17983632
Reaction time; Poffenberger paradigm; Interhemispheric transfer; Spatial attention; Task context
4.  Neural Basis of Self and Other Representation in Autism: An fMRI Study of Self-Face Recognition 
PLoS ONE  2008;3(10):e3526.
Background
Autism is a developmental disorder characterized by decreased interest and engagement in social interactions and by enhanced self-focus. While previous theoretical approaches to understanding autism have emphasized social impairments and altered interpersonal interactions, there is a recent shift towards understanding the nature of the representation of the self in individuals with autism spectrum disorders (ASD). Still, the neural mechanisms subserving self-representations in ASD are relatively unexplored.
Methodology/Principal Findings
We used event-related fMRI to investigate brain responsiveness to images of the subjects' own face and to faces of others. Children with ASD and typically developing (TD) children viewed randomly presented digital morphs between their own face and a gender-matched other face, and made “self/other” judgments. Both groups of children activated a right premotor/prefrontal system when identifying images containing a greater percentage of the self face. However, while TD children showed activation of this system during both self- and other-processing, children with ASD only recruited this system while viewing images containing mostly their own face.
Conclusions/Significance
This functional dissociation between the representation of self versus others points to a potential neural substrate for the characteristic self-focus and decreased social understanding exhibited by these individuals, and suggests that individuals with ASD lack the shared neural representations for self and others that TD children and adults possess and may use to understand others.
doi:10.1371/journal.pone.0003526
PMCID: PMC2568959  PMID: 18958161
5.  Fast Visuomotor Processing of Redundant Targets: The Role of the Right Temporo-Parietal Junction 
PLoS ONE  2008;3(6):e2348.
Parallel processing of multiple sensory stimuli is critical for efficient, successful interaction with the environment. An experimental approach to studying parallel processing in sensorimotor integration is to examine reaction times to multiple copies of the same stimulus. Reaction times to bilateral copies of light flashes are faster than to single, unilateral light flashes. These faster responses may be due to ‘statistical facilitation’ between independent processing streams engaged by the two copies of the light flash. On some trials, however, reaction times are faster than predicted by statistical facilitation. This indicates that a neural ‘coactivation’ of the two processing streams must have occurred. Here we use fMRI to investigate the neural locus of this coactivation. Subjects responded manually to the detection of unilateral light flashes presented to the left or right visual hemifield, and to the detection of bilateral light flashes. We compared the bilateral trials where subjects' reaction times exceeded the limit predicted by statistical facilitation to bilateral trials that did not exceed the limit. Activity in the right temporo-parietal junction was higher in those bilateral trials that showed coactivation than in those that did not. These results suggest the neural coactivation observed in visuomotor integration occurs at a cognitive rather than sensory or motor stage of processing.
doi:10.1371/journal.pone.0002348
PMCID: PMC2390848  PMID: 18523591
6.  rTMS to the right inferior parietal lobule disrupts self–other discrimination 
Self–other discrimination is fundamental to social interaction, however, little is known about the neural systems underlying this ability. In a previous functional magnetic resonance imaging study, we demonstrated that a right fronto-parietal network is activated during viewing of self-faces as compared with the faces of familiar others. Here we used image-guided repetitive transcranial magnetic stimulation (rTMS) to create a ’virtual lesion’ over the parietal component of this network to test whether this region is necessary for discriminating self-faces from other familiar faces. The current results indeed show that 1 Hz rTMS to the right inferior parietal lobule (IPL) selectively disrupts performance on a self–other discrimination task. Applying 1 Hz rTMS to the left IPL had no effect. It appears that activity in the right IPL is essential to the task, thus providing for the first time evidence for a causal relation between a human brain area and this high-level cognitive capacity.
doi:10.1093/scan/nsl003
PMCID: PMC1832105  PMID: 17387382
self-awareness; self-recognition; social cognition; inferior parietal lobule; mirror neurons
7.  Dichotic Listening after Cerebral Hemispherectomy: Methodological and Theoretical Observations 
Neuropsychologia  2007;45(11):2461-2466.
We examined two commonly used dichotic listening tests for measuring the degree of hemispheric specialization for language in individuals who had undergone cerebral hemispherectomy: the Consonant-Vowel (CV) nonsense syllables and the Fused Words (FW) tests, using the common laterality indices f and λ. Hemispherectomy on either side resulted in a massive contralateral ear advantage, demonstrating nearly complete ipsilateral suppression of the left ear in the right hemispherectomy group but slightly less complete suppression of the right ear in the left hemispherectomy group. The results are consistent with the anatomical model of the ear advantage (Kimura, 1961). Most syllables or words are reported for the ear contralateral to the remaining hemisphere, while few or none are reported for the ear ipsilateral to the remaining hemisphere. In the presence of competing inputs to the two ears, the stronger contralateral ear-hemisphere connection dominates/suppresses the weaker ipsilateral ear-hemisphere connection. The λ index was similar in the two tests but the index f was higher in the CV than the FW test. Both indices of the CV test were sensitive to side of resection, higher in the right hemispherectomy than in the left hemispherectomy groups.
doi:10.1016/j.neuropsychologia.2007.03.026
PMCID: PMC1948872  PMID: 17512023
8.  rTMS to the right inferior parietal lobule disrupts self–other discrimination 
Self–other discrimination is fundamental to social interaction, however, little is known about the neural systems underlying this ability. In a previous functional magnetic resonance imaging study, we demonstrated that a right fronto-parietal network is activated during viewing of self-faces as compared with the faces of familiar others. Here we used image-guided repetitive transcranial magnetic stimulation (rTMS) to create a ‘virtual lesion’ over the parietal component of this network to test whether this region is necessary for discriminating self-faces from other familiar faces. The current results indeed show that 1 Hz rTMS to the right inferior parietal lobule (IPL) selectively disrupts performance on a self–other discrimination task. Applying 1 Hz rTMS to the left IPL had no effect. It appears that activity in the right IPL is essential to the task, thus providing for the first time evidence for a causal relation between a human brain area and this high-level cognitive capacity.
doi:10.1093/scan/nsl003
PMCID: PMC1832105  PMID: 17387382
self-awareness; self-recognition; social cognition; inferior parietal lobule; mirror neurons
9.  The neural correlates of social attention: automatic orienting to social and nonsocial cues 
Psychological Research  2009;73(4):499-511.
Previous evidence suggests that directional social cues (e.g., eye gaze) cause automatic shifts in attention toward gaze direction. It has been proposed that automatic attentional orienting driven by social cues (social orienting) involves a different neural network from automatic orienting driven by nonsocial cues. However, previous neuroimaging studies on social orienting have only compared gaze cues to symbolic cues, which typically engage top-down mechanisms. Therefore, we directly compared the neural activity involved in social orienting to that involved in purely automatic nonsocial orienting. Twenty participants performed a spatial cueing task consisting of social (gaze) cues and automatic nonsocial (peripheral squares) cues presented at short and long stimulus (cue-to-target) onset asynchronies (SOA), while undergoing fMRI. Behaviorally, a facilitation effect was found for both cue types at the short SOA, while an inhibitory effect (inhibition of return: IOR) was found only for nonsocial cues at the long SOA. Imaging results demonstrated that social and nonsocial cues recruited a largely overlapping fronto-parietal network. In addition, social cueing evoked greater activity in occipito-temporal regions at both SOAs, while nonsocial cueing recruited greater subcortical activity, but only for the long SOA (when IOR was found). A control experiment, including central arrow cues, confirmed that the occipito-temporal activity was at least in part due to the social nature of the cue and not simply to the location of presentation (central vs. peripheral). These results suggest an evolutionary trajectory for automatic orienting, from predominantly subcortical mechanisms for nonsocial orienting to predominantly cortical mechanisms for social orienting.
doi:10.1007/s00426-009-0233-3
PMCID: PMC2694932  PMID: 19350270

Results 1-9 (9)