Insular Cortex Mediates Attentional Capture by Behaviorally Relevant Stimuli after Damage to the Right Temporoparietal Junction.

The right temporoparietal junction (rTPJ) and insula both play a key role for the processing of relevant stimuli. However, while both have been conceived as neural "switches" that detect salient events and redirect the focus of attention, it remains unclear how these brain regions interact to achieve this behavioral goal. Here, we tested human participants with focal left-hemispheric or right-hemispheric lesions in a spatial cuing task that requires participants to react to lateralized stimuli preceded by a distracter that shares or does not share a relevant feature with the target. Using machine learning to identify significant lesion-behavior relationships, we found that rTPJ damage produces distinctive, pathologically increased attentional capture, but only by relevant distracters. Functional connectivity analyses revealed that the degree of capture is positively associated with a functional connection between insula and rTPJ, together with functional isolation of the rTPJ from right dorsal prefrontal cortex (dPFC). These findings suggest a mechanistic model where the insula-rTPJ connection constitutes a crucial functional unit that breaks attentional focus upon detection of behaviorally relevant events, while the dPFC appears to attune this activity.

Comparison of Neuroplastic Responses to Cathodal Transcranial Direct Current Stimulation and Continuous Theta Burst Stimulation in Subacute Stroke.

OBJECTIVE: To investigate the effects of cathodal transcranial direct current stimulation (tDCS) and continuous theta burst stimulation (cTBS) on neural network connectivity and motor recovery in individuals with subacute stroke. DESIGN: Double-blinded, randomized, placebo-controlled study. SETTING: University hospital rehabilitation unit. PARTICIPANTS: Inpatients with stroke (N=41; mean age, 65y; range, 28-85y; mean weeks poststroke, 5; range, 2-10) with resultant paresis in the upper extremity (mean Fugl-Meyer score, 14; range, 3-48). INTERVENTIONS: Subjects with stroke were randomly assigned to neuronavigated cTBS (n=14), cathodal tDCS (n=14), or sham transcranial magnetic stimulation/sham tDCS (n=13) over the contralesional primary motor cortex (M1). Each subject completed 9 stimulation sessions over 3 weeks, combined with physical therapy. MAIN OUTCOME MEASURES: Brain function was assessed with directed and nondirected functional connectivity based on high-density electroencephalography before and after stimulation sessions. Primary clinical end point was the change in slope of the multifaceted motor score composed of the upper extremity Fugl-Meyer Assessment score, Box and Block test score, 9-Hole Peg Test score, and Jamar dynamometer results between the baseline period and the treatment time. RESULTS: Neither stimulation treatment enhanced clinical motor gains. Cathodal tDCS and cTBS induced different neural effects. Only cTBS was able to reduce transcallosal influences from the contralesional to the ipsilesional M1 during rest. Conversely, tDCS enhanced perilesional beta-band oscillation coherence compared with cTBS and sham groups. Correlation analyses indicated that the modulation of interhemispheric driving and perilesional beta-band connectivity were not independent mediators for functional recovery across all patients. However, exploratory subgroup analyses suggest that the enhancement of perilesional beta-band connectivity through tDCS might have more robust clinical gains if started within the first 4 weeks after stroke. CONCLUSIONS: The inhibition of the contralesional M1 or the reduction of interhemispheric interactions was not clinically useful in the heterogeneous group of subjects with subacute stroke. An early modulation of perilesional oscillation coherence seems to be a more promising strategy for brain stimulation interventions.

The neuroanatomy of spatial awareness: a large-scale region-of-interest and voxel-based anatomical study.

Lesion-symptom studies of spatial neglect and the attention deficits associated with this disorder draw a complex picture of the brain areas involved in spatial awareness. Several cortical regions and fiber tracts have been identified as predictors of behavioral performance, a pattern reflecting the large degree of methodological variance and modest sample sizes of many studies. Here, we examined the anatomical predictors of deficits of spatial exploration, reading and line bisection in 134 unselected stroke patients with post-acute, right-hemispheric brain injury. In order to neutralize shortcomings of traditional lesion-symptom analyses we used several methodological approaches: voxel-based lesion-symptom mapping focusing on binary groups or continuous performance measures, region-of-interest analyses and a 'minimal-lesion' method, comparing patients with highly selective deficits to specific brain areas. All four approaches converged on the central role of the right temporo-parietal junction and frontoparietal connections conveyed through the superior longitudinal fasciculus for contralateral deployment of attention and detection of task-relevant stimuli.

Damage to the right temporoparietal junction, but not lateral prefrontal or insular cortex, amplifies the role of goal-directed attention.

Whether an object captures attention depends on the interplay between its saliency and current behavioral predispositions of the observer. Neuroimaging work has implied a ventral attention network, comprising the temporoparietal junction (TPJ), lateral prefrontal cortex (lPFC) and the insula, in attentional orienting toward salient events. Activity of the TPJ is driven by novel and unexpected objects, while the lateral prefrontal cortex is involved in stimulus-driven as well as goal-directed processing. The insula in turn, is part of a saliency network, which has been implicated in detecting biologically salient signals. These roles predict that damage to the TPJ, lPFC, or insula should affect performance in tasks measuring the capture of attention by salient and behaviorally relevant events. Here, we show that patients with lesions to the right TPJ have a characteristic increase of attentional capture by relevant distracters. In contrast, damage to the lPFC or insular cortex only increases reaction times, irrespective of the task-relevant properties of distracters. These findings show that acquired damage to the TPJ pathologically amplifies the capture of attention by task-relevant information, and thus indicate that the TPJ has a decisive role in goal-directed orienting.

Neural correlates of reality filtering in schizophrenia spectrum disorder.

BACKGROUND: A false sense of reality is a characteristic of schizophrenia spectrum disorders (SSD). Reality confusion may also emanate from posterior orbitofrontal cortex (OFC) lesions, as evident in confabulations that patients act upon and disorientation. This confusion can be measured by repeated runs of a continuous recognition task (CRT): patients increase their false positive rate from the second run on, failing to realize that an item is not a repetition within the current run. Correct handling of these stimuli, a faculty called orbitofrontal reality filtering (ORFi), induces a distinct frontal potential at 200-300 ms, the "ORFi potential". Patients with schizophrenia have been reported to fail in this task, too. Here, we explored the electrophysiology of ORFi in SSD. METHODS: Evoked potentials, source, and connectivity analyses derived from high-density electroencephalograms of 17 patients with SSD and 15 age-matched healthy controls performing two runs of a CRT. RESULTS: Although the patients obtained normal performance, they did not normally express the frontal potential typical of ORFi between 200 and 300 ms. Coherence analysis demonstrated virtually absent functional connectivity in the theta band within the memory network in this period. Source analysis showed increased activity in left medial temporal and prefrontal regions in patients. CONCLUSIONS: SSD patients appear to invoke compensatory resources to handle the challenges of reality filtering. An abnormal ORFi potential may be an early biomarker of SSD.

A neuroanatomical model of space-based and object-centered processing in spatial neglect.

Visual attention can be deployed in space-based or object-centered reference frames. Right-hemisphere damage may lead to distinct deficits of space- or object-based processing, and such dissociations are thought to underlie the heterogeneous nature of spatial neglect. Previous studies have suggested that object-centered processing deficits (such as in copying, reading or line bisection) result from damage to retro-rolandic regions while impaired spatial exploration reflects damage to more anterior regions. However, this evidence is based on small samples and heterogeneous tasks. Here, we tested a theoretical model of neglect that takes in account the space- and object-based processing and relates them to neuroanatomical predictors. One hundred and one right-hemisphere-damaged patients were examined with classic neuropsychological tests and structural brain imaging. Relations between neglect measures and damage to the temporal-parietal junction, intraparietal cortex, insula and middle frontal gyrus were examined with two structural equation models by assuming that object-centered processing (involved in line bisection and single-word reading) and space-based processing (involved in cancelation tasks) either represented a unique latent variable or two distinct variables. Of these two models the latter had better explanatory power. Damage to the intraparietal sulcus was a significant predictor of object-centered, but not space-based processing, while damage to the temporal-parietal junction predicted space-based, but not object-centered processing. Space-based processing and object-centered processing were strongly intercorrelated, indicating that they rely on similar, albeit partly dissociated processes. These findings indicate that object-centered and space-based deficits in neglect are partly independent and result from superior parietal and inferior parietal damage, respectively.

Electrophysiological correlates of visual binding errors after bilateral parietal damage.

Illusory conjunctions (e.g. the confusion between the shape of one stimulus with the color of another stimulus) are the most dramatic expression of binding failures in vision. Under brief exposure or when attention is diverted illusory conjunctions may be observed in healthy participants, but they only represent a real-life problem for patients with parietal damage. However, it is unclear whether such failures reflect the impairment of early or late stages of visual processing. Here, we examined the time-course of visual processing using evoked potential measures in a patient with bilateral damage to the posterior parietal cortex presenting prominent binding failures. The patient was asked to identify colored letters that were briefly flashed to the left or right hemifield. When only one item was presented she adequately identified color or shape of left and right letters. In contrast, when presentation was bilateral she either identified the correct right shape-color combination and missed the item in the left hemifield (extinction) or combined incorrectly the right shape with the left color (illusory conjunction). Evoked potential analyses revealed a specific electrophysiological signature of illusory conjunctions, starting ∼105ms after stimulus onset over the right frontal cortex. These findings indicate that binding errors reflect failures of early stages of attentional filtering relying on the integrity of the posterior parietal cortex.