Linguistic Empathy: Behavioral measures, neurophysiological correlates, and correlation with Psychological Empathy.

Relations among behavioral, psychological, and electrophysiological correlates of Linguistic Empathy were examined in two experiments using lateralized stimuli. Linguistic Empathy is defined as a linguistic manifestation of the point of view the speaker assumes toward the content of the utterance, and of the speaker's attitude toward/identification with the referents therein. Linguistic choices made by the speaker among multiple logically and referentially synonymous lexical and grammatical options reveal the speaker's perspectives. In experiment 1, acceptability ratings were measured for Context-Target sentence pairs that did or did not violate two Empathy Hierarchies (Person Empathy Hierarchy and Topic Empathy Hierarchy); the Empathy Quotient (EQ) test of Psychological Empathy was also administered. Ratings were lower for sentence pairs that violated both hierarchies than for those violating neither and were intermediate for sentences violating only one hierarchy. Linguistic Empathy (LE) was operationalized as the difference in ratings between sentences violating both vs. neither empathy hierarchy; this measure correlated positively with EQ. Experiment 2 replicated those results with new participants and measured reaction time and EEG during ratings. While there were no effects of hemisphere or visual field on the linguistic variables, the amplitude of a positive event-related potential deflection at 380 ms provided a partial electrophysiological correlate for LE. Its difference measure correlated with behavioral LE but not with EQ. Though preliminary, these experiments show that Linguistic Empathy may share information processing computations with Psychological Empathy and have an electrophysiological correlate.

Group differences between practitioners and novices in hemispheric processing of attention and emotion before and after a session of Falun Gong qigong.

We examined the hemispheric effects of Falun Gong qigong (FLG), a movement meditation practice, using a systematic approach to hemispheric function by administering the Emotion Lateralized Attention Network Test (ELANT) to measure the interaction of the Conflict Resolution, Spatial Orienting, and Emotion networks. Measuring both behavior (ELANT, DV = accuracy) and physiology (HF-HRV), we compared experienced FLG practitioners (n = 19) to novices serving as an active control group (n = 16) before and after a 91-min sequence of FLG qigong exercises. We compared practitioners and novices using a hierarchy of intrahemispheric and interhemispheric control relations that can be tested with the ELANT. Practitioners exhibited a prominent short-term effect in which they improved relative to novices on trials requiring complex interhemispheric transfer (ηP2 = 0.21). Two baseline group differences, suggesting long-term effects of FLG, both involved the left hemisphere. First, practitioners were selectively spared the negative effects of processing positive emotion cues preceding left hemisphere targets (ηP2 = 0.34). Second, only practitioners showed improved left-hemisphere Conflict Resolution at higher levels of HF-HRV (r2 = 0.40). The data showed that FLG practitioners had increased flexibility in the management of a limited attentional resource pool that is accessible to both hemispheres.

Diffusion weighted imaging evidence of extra-callosal pathways for interhemispheric communication after complete commissurotomy.

The integrity of white matter architecture in the human brain is related to cognitive processing abilities. The corpus callosum is the largest white matter bundle interconnecting the two cerebral hemispheres. "Split-brain" patients in whom all cortical commissures have been severed to alleviate intractable epilepsy demonstrate remarkably intact cognitive abilities despite the lack of this important interhemispheric pathway. While it has often been speculated that there are compensatory alterations in the remaining interhemispheric fibers in split-brain patients several years post-commissurotomy, this has never been directly shown. Here we examined extra-callosal pathways for interhemispheric communication in the brain of a patient who underwent complete cerebral commissurotomy using diffusion weighted imaging tractography. We found that compared with a healthy age-matched comparison group, the split-brain patient exhibited increased fractional anisotropy (FA) of the dorsal and ventral pontine decussations of the cortico-cerebellar interhemispheric pathways. Few differences were observed between the patient and the comparison group with respect to FA of other long-range intrahemispheric fibers. These results point to specific cerebellar anatomical substrates that may account for the spared interhemispheric coordination and intact cognitive abilities that have been extensively documented in this unique patient.

Intrinsic functional organization of putative language networks in the brain following left cerebral hemispherectomy.

In rare cases of severe and intractable epilepsy, cerebral hemispherectomy is performed to arrest seizure activity and improve quality of life. The remaining hemisphere is often capable of supporting many cognitive functions post-surgery, although the outcome depends on the underlying etiology, hemisphere removed, and age of resection. The mechanisms underlying this massive reorganization are at present unknown. Here we examined intrinsic functional connectivity of putative language brain networks in four children after left cerebral hemispherectomy using resting-state functional magnetic resonance imaging (rsfMRI). We compared these functional systems to intrinsic language networks in 15 neurotypical controls using region-of-interest (ROI)-based functional connectivity analyses. In three out of four hemispherectomy patients, the ROI placed in the right inferior gyrus revealed a functional network that strongly resembled the right-hemisphere intrinsic language network observed in controls. This network typically comprised inferior frontal gyrus, superior temporal sulcus, and premotor regions. Quantitative ROI-to-ROI analyses revealed that functional connectivity between major nodes of the language network was significantly altered in all 4 examined patients. Overall, our data demonstrate that the pattern of functional connectivity within language networks is at least partially preserved in the intact right hemisphere of patients who underwent left hemispherectomy.

Focus on the positive: anxiety modulates the effects of emotional stimuli on hemispheric attention.

People with high levels of trait anxiety are said to orient attention selectively to threatening stimuli (Bradley, Mogg, White, Groom, & de Bono, 1999; MacLeod, Mathews, & Tata, 1986), but this effect is sometimes difficult to replicate. We suggest a reason for this difficulty is that typical tests of the spatial attention bias in anxiety failed to consider together: (1) the differential effects of positive and threatening stimuli on attention in anxiety, (2) the separate contributions of each hemisphere to the attention bias, and (3) whether the attention bias in anxiety is restricted to orienting or can be observed more strongly in the conflict or alerting networks of attention. We compared the effects of schematic angry, happy, and neutral face cues using a lateralized version of Posner's Attention Network Task (Lateralized Attention Network Test) which distinguishes spatial Orienting Cost (due to an invalid cue; disengagement) from spatial Orienting Benefit (due to a valid cue; hypervigilance), and which considers executive Conflict resolution and Alerting in addition to spatial Orienting in each hemisphere separately. We tested participants with high and low trait anxiety measured by the STAI-TA (Spielberger, Gorsuch, & Lushene, 1983). Surprisingly, happy face cues rather than angry face cues interacted with target visual field and participant level of anxiety. Happy face cues presented to participants with low anxiety elicited maximal Orienting Benefit and minimal Orienting Cost for targets presented to the left visual field. Anxious individuals failed to benefit from happy cues in the left visual field. We suggest that lateralized positive cues can provide a more sensitive index of attention changes in anxiety than is provided by centrally-presented threatening cues.

Spatial orienting of attention simultaneously cued by automatic social and nonsocial cues.

The appearance of a stimulus in the periphery and the direction of another person's eye gaze have both been shown to automatically orient attention toward the stimulus and the gazed-at location, respectively. In the present experiment, we examined the effects of viewing both a peripheral stimulus and an eye gaze stimulus simultaneously in order to determine whether one is "more automatic" (i.e., faster, dominates) than the other and whether the two processes interact. Using a spatial cueing paradigm, we measured latency of localization of a target stimulus that was validly or invalidly cued by an uninformative (i.e., nonpredictive) peripheral cue, an uninformative eye gaze cue, or both simultaneously (double cue). We included a short and a long cue-target interval in order to investigate the early and late facilitatory and inhibitory effects of the two processes. Results demonstrated that when the double cues were consistent with each other (indicating the same target location), the effects, both early and late, were the same as when the peripheral cue was presented alone. When the double cues were inconsistent (indicating opposite target locations), the late effect was the same as the peripheral cue, but the early effect was intermediate between the two types of cues. Our results better support an interactive, rather than an additive relationship between social and nonsocial automatic orienting. The double cue conditions that showed similar effects to the peripheral cues suggest that the peripheral cue dominates.

Hemispheric integration is critical for intact error processing.

We provide for the first time direct clinical evidence for the critical role of hemispheric integration in intact error processing. We tested three patients with partial callosal disconnection. Two anterior patients could not correct their errors in a unilateral version of a visuomotor learning task for which they previously exhibited callosal disconnection, whereas, they corrected most of their errors in two visual matching tasks (comparing abstract shapes or faces) that they could transfer between the hemispheres. An opposite pattern emerged in a posterior patient. He could not correct his errors in unilateral versions of the same visual matching tasks, for which he previously exhibited callosal disconnection. However, he corrected most of his errors in the visuomotor learning task he was able to transfer between the hemispheres.

Atypical neural networks for social orienting in autism spectrum disorders.

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.

Hemispheric differences in attentional orienting by social cues.

Research points to a right hemisphere bias for processing social stimuli. Hemispheric specialization for attention shifts cued by social stimuli, however, has been rarely studied. We examined the capacity of each hemisphere to orient attention in response to social and nonsocial cues using a lateralized spatial cueing paradigm. We compared the up/down orienting effects of eye gaze cues, arrow cues, and peripheral cues (change in luminance). Results revealed similar cueing effects in each visual field for nonsocial cues, but asymmetric effects for social cues. At both short (150 ms) and long (950 ms) cue-target intervals, gaze cueing was significant in the LVF, but not in the RVF. Thus, there is a right hemisphere bias for attentional orienting cued by social stimuli, but not for attentional orienting cued by nonsocial stimuli. This supports a theory of a separate neural system for socially cued orienting of attention, as well as a theory of separate parallel and simultaneous neural systems for attention in the two cerebral hemispheres.

The neural correlates of social attention: automatic orienting to social and nonsocial cues.

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.

Spatial attention and interhemispheric visuomotor integration in the absence of the corpus callosum.

In the lateralized simple reaction time (SRT) task with unimanual responses (Poffenberger paradigm), 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) has typically been interpreted to reflect callosal transfer time. Indeed, acallosal subjects and split-brain subjects have longer CUDs than control subjects. However, a few recent studies have demonstrated that, contrary to classical findings, the CUD is also affected by non-anatomical factors. Here we show that the CUD is also affected by non-anatomical factors in patients with agenesis of the corpus callosum and complete commissurotomy where interhemispheric transfer must be subcallosal. We tested acallosal subject M.M. and split brain patient A.A. on a lateralized SRT task with their arms alternately uncrossed (natural arms position) or crossed (unnatural arms position) across blocks of trials. The results revealed a significant effect of arms crossing on the size and direction of the CUD as previously found in normal subjects [Mooshagian, E., Iacoboni, M., & Zaidel, E. (2008). The role of task history in simple reaction time to lateralized light flashes. Neuropsychologia, 46(2), 659-664]. This suggests that non-anatomical factors that modulate interhemispheric visuomotor integration may occur in absence of the corpus callosum. Anterior commissure and interhemispheric cortico-subcortical pathways are likely implicated in these effects.

Rethinking a right hemisphere deficit in ADHD.

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 interhemispheric interaction. If true, RH pathology in ADHD should reflect interhemispherically networked and overactivated functioning. The authors evaluated these assertions. METHOD: 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, the authors 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. CONCLUSION: Interhemispherically networked RH processing is critical in ADHD. In addition, lack of association between LH specialized processing and cognitive ability (especially for verbal cognitive tasks) supports increased RH mediation of task processing.

Neural basis of self and other representation in autism: an FMRI study of self-face recognition.

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.

Fast visuomotor processing of redundant targets: the role of the right temporo-parietal junction.

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.

Residual functional connectivity in the split-brain revealed with resting-state functional MRI.

Split-brain patients present a unique opportunity to address controversies regarding subcortical contributions to interhemispheric coordination. We characterized residual functional connectivity in a complete commissurotomy patient by examining patterns of low-frequency BOLD functional MRI signal. Using independent components analysis and region-of-interest-based functional connectivity analyses, we demonstrate bilateral resting state networks in a patient lacking all major cerebral commissures. Compared with a control group, the patient's interhemispheric correlation scores fell within the normal range for two out of three regions examined. Thus, we provide evidence for bilateral resting state networks in a patient with complete commissurotomy. Such continued interhemispheric interaction suggests that, at least in part, cortical networks in the brain can be coordinated by subcortical mechanisms.

Measuring attention in the hemispheres: the lateralized attention network test (LANT).

The attention network test (ANT) is a brief computerized battery measuring three independent behavioral components of attention: Conflict resolution (ability to overcome distracting stimuli), spatial Orienting (the benefit of valid spatial pre-cues), and Alerting (the benefit of temporal pre-cues). Imaging, clinical, and behavioral evidence demonstrate hemispheric asymmetries in these attentional networks. We constructed a lateralized version of the ANT (LANT), with brief targets flashed in one or the other visual hemifield. We also modified the tests by including invalid spatial cues in order to measure the cost component of Orienting. In a series of experiments, we investigated the efficiency of the attention networks separately in each hemisphere. Participants exhibited significant estimates of all networks measured by the LANT, comparable to the ANT. The three networks were represented in each hemisphere separately and were largely comparable across the two hemispheres. We suggest that the LANT is an informative extension of the original ANT, allowing for measurement of the three attention networks in each hemisphere separately.

The role of task history in simple reaction time to lateralized light flashes.

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.

Speech-independent production of communicative gestures: evidence from patients with complete callosal disconnection.

Recent neuropsychological, psycholinguistic, and evolutionary theories on language and gesture associate communicative gesture production exclusively with left hemisphere language production. An argument for this approach is the finding that right-handers with left hemisphere language dominance prefer the right hand for communicative gestures. However, several studies have reported distinct patterns of hand preferences for different gesture types, such as deictics, batons, or physiographs, and this calls for an alternative hypothesis. We investigated hand preference and gesture types in spontaneous gesticulation during three semi-standardized interviews of three right-handed patients and one left-handed patient with complete callosal disconnection, all with left hemisphere dominance for praxis. Three of them, with left hemisphere language dominance, exhibited a reliable left-hand preference for spontaneous communicative gestures despite their left hand agraphia and apraxia. The fourth patient, with presumed bihemispheric language representation, revealed a consistent right-hand preference for gestures. All four patients displayed batons, tosses, and shrugs more often with the left hand/shoulder, but exhibited a right hand preference for pantomime gestures. We conclude that the hand preference for certain gesture types cannot be predicted by hemispheric dominance for language or by handedness. We found distinct hand preferences for specific gesture types. This suggests a conceptual specificity of the left and right hand gestures. We propose that left hand gestures are related to specialized right hemisphere functions, such as prosody or emotion, and that they are generated independently of left hemisphere language production. Our findings challenge the traditional neuropsychological and psycholinguistic view on communicative gesture production.

Dichotic listening after cerebral hemispherectomy: methodological and theoretical observations.

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 lambda. 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, D. (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 lambda 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.

The effects of bilateral presentations on lateralized lexical decision.

We investigated how lateralized lexical decision is affected by the presence of distractors in the visual hemifield contralateral to the target. The study had three goals: first, to determine how the presence of a distractor (either a word or a pseudoword) affects visual field differences in the processing of the target; second, to identify the stage of the process in which the distractor is affecting the decision about the target; and third, to determine whether the interaction between the lexicality of the target and the lexicality of the distractor ("lexical redundancy effect") is due to facilitation or inhibition of lexical processing. Unilateral and bilateral trials were presented in separate blocks. Target stimuli were always underlined. Regarding our first goal, we found that bilateral presentations (a) increased the effect of visual hemifield of presentation (right visual field advantage) for words by slowing down the processing of word targets presented to the left visual field, and (b) produced an interaction between visual hemifield of presentation (VF) and target lexicality (TLex), which implies the use of different strategies by the two hemispheres in lexical processing. For our second goal of determining the processing stage that is affected by the distractor, we introduced a third condition in which targets were always accompanied by "perceptual" distractors consisting of sequences of the letter "x" (e.g., xxxx). Performance on these trials indicated that most of the interaction occurs during lexical access (after basic perceptual analysis but before response programming). Finally, a comparison between performance patterns on the trials containing perceptual and lexical distractors indicated that the lexical redundancy effect is mainly due to inhibition of word processing by pseudoword distractors.