Joint impact on attention, alertness and inhibition of lesions at a frontal white matter crossroad.

In everyday life, information from different cognitive domains-such as visuospatial attention, alertness and inhibition-needs to be integrated between different brain regions. Early models suggested that completely segregated brain networks control these three cognitive domains. However, more recent accounts, mainly based on neuroimaging data in healthy participants, indicate that different tasks lead to specific patterns of activation within the same, higher-order and 'multiple-demand' network. If so, then a lesion to critical substrates of this common network should determine a concomitant impairment in all three cognitive domains. The aim of the present study was to critically investigate this hypothesis, i.e. to identify focal stroke lesions within the network that can concomitantly affect visuospatial attention, alertness and inhibition. We studied an unselected sample of 60 first-ever right-hemispheric, subacute stroke patients using a data-driven, bottom-up approach. Patients performed 12 standardized neuropsychological and oculomotor tests, four per cognitive domain. A principal component analysis revealed a strong relationship between all three cognitive domains: 10 of 12 tests loaded on a first, common component. Analysis of the neuroanatomical lesion correlates using different approaches (i.e. voxel-based and tractwise lesion-symptom mapping, disconnectome maps) provided convergent evidence on the association between severe impairment of this common component and lesions at the intersection of superior longitudinal fasciculus II and III, frontal aslant tract and, to a lesser extent, the putamen and inferior fronto-occipital fasciculus. Moreover, patients with a lesion involving this region were significantly more impaired in daily living cognition, which provides an ecological validation of our results. A probabilistic functional atlas of the multiple-demand network was performed to confirm the potential relationship between patients' lesion substrates and observed cognitive impairments as a function of the multiple-demand network connectivity disruption. These findings show, for the first time, that a lesion to a specific white matter crossroad can determine a concurrent breakdown in all three considered cognitive domains. Our results support the multiple-demand network model, proposing that different cognitive operations depend on specific collaborators and their interaction, within the same underlying neural network. Our findings also extend this hypothesis by showing (i) the contribution of superior longitudinal fasciculus and frontal aslant tract to the multiple-demand network; and (ii) a critical neuroanatomical intersection, crossed by a vast amount of long-range white matter tracts, many of which interconnect cortical areas of the multiple-demand network. The vulnerability of this crossroad to stroke has specific cognitive and clinical consequences; this has the potential to influence future rehabilitative approaches.

Left hemispheric epilepsy is more frequent and has worse clinical course that right hemispheric epilepsy.

INTRODUCTION: Few studies demonstrated that focal epilepsy (FE) with left hemispheric (LH) seizure onset is more frequent than with right hemispheric (RH) seizure onset. In addition, patients with LH seizure onset show worse clinical course compared to those with RH seizure onset. The aim of our study was to investigate both issues in a great cohort of FE patients. METHODS: In the retrospective study, we reviewed the clinical and paraclinical data of 682 patients with exclusively LH or RH seizure onset. We ascertained the laterality of seizure onset mainly by ictal and postictal semiology and ictal EEG findings. In the absence of ictal data, the basis of lateralization was the evidence of unilateral structural brain abnormality together with a corresponding interictal EEG finding. The endpoint of analysis of the clinical course was the presence/absence of five-year remission on drug treatment in the first ten years of treatment. RESULTS: Out of the 682 patients, 378 (55.4 per cent) had LH and 304 (44.6 per cent) had RH seizure onset. The difference was statistically significant (p = 0.04). Out of them, 213 LH and 156 RH patients were eligible to evaluate prognosis. Five-years-remission was attained by 71 patients (33.3 per cent) in the LH, and 65 (41.7 per cent) in the RH group. The difference was statistically significant (p = 0.05). CONCLUSION: We demonstrated the LH dominance of seizure onset and the worse clinical course of the patients with LH seizure onset. The findings are manifestations of the lateralized epileptic propensity of the brain. The dissimilar clinical course of the patient with LH and RH seizure onset may shape the general prognostic scheme in FE patients.

A leftward bias negatively correlated with performance is selectively displayed by domestic chicks during rule reversal (not acquisition).

In order to face a constantly changing environment, animals need to be able to update their knowledge of the world on the basis of new information. Often, this means to inhibit a previously acquired response and flexibly change their behaviour to produce a new response. Here, we measured such abilities in young domestic chicks, employing a Colour Reversal Learning Task. During the acquisition phase, 17 one-week-old male chicks had to learn to peck on one of two coloured boxes to obtain a food reward. After reaching criterion, chicks underwent a reversal phase in which the previously learned colour-reward contingency was swapped. As expected from the literature, chicks performed better in the acquisition phase with respect to the reversal phase. Results moreover highlighted the presence of a lateralized bias selectively during reversal: chicks performed better if the stimulus rewarded was located in the left hemispace (processed by the right hemisphere). Interestingly, the bias correlated with the individual difficulty, i.e., it was stronger in those chicks which needed more trials to complete the reversal session. The present study contributes evidence in support of behavioural flexibility in young chicks, along with a novel perspective on lateralized mechanisms that might underlie such ability.

Theta burst stimulation in neglect after stroke: functional outcome and response variability origins.

Spatial neglect is a strong and negative predictor of general functional outcome after stroke, and its therapy remains a challenge. Whereas inhibitory non-invasive brain stimulation over the contralesional, intact hemisphere has generally been shown to ameliorate neglect on a group level, a conspicuous variability of the effects at the individual level is typically observed. We aimed to assess the characteristics and determinants of the effects of inhibitory non-invasive brain stimulation in neglect, identifying which patients would respond to this therapeutic approach and which not. To this end, we prospectively included 60 patients with a subacute right-hemispheric stroke. In 30 patients with spatial neglect, continuous theta burst stimulation (cTBS) was applied over the left posterior parietal cortex in a randomized clinical trial, either in eight or 16 trains, or as sham stimulation. Thirty patients without neglect served as a control group. Neglect severity was measured with a neuropsychological test battery and the Catherine Bergego Scale, at admission to and at discharge from inpatient neurorehabilitation, as well as at 3 months follow-up. General functional outcome was assessed by means of the Functional Independence Measure and the Lucerne ICF-based Multidisciplinary Observation Scale. The impact of clinical and demographic factors was evaluated, and the influence of lesion location and extension was assessed by means of voxel-based lesion-symptom mapping. On a group level, both cTBS protocols (i.e. eight and 16 trains) significantly reduced neglect severity in both the Catherine Bergego Scale and the neuropsychological tests, at discharge and 3 months later. Furthermore, cTBS significantly improved general functional outcome. On an individual level, hierarchical cluster and voxel-based lesion-symptom mapping analyses revealed that the variability in the responses to cTBS is determined by the integrity of interhemispheric connections within the corpus callosum, in particular parieto-parietal connections. In cTBS responders, in whom neglect and general functional outcome were significantly improved, the corpus callosum was intact, whereas this was not the case in cTBS non-responders. Moreover, analyses based on the proportional recovery rule and the Maugeri predictive stroke recovery model showed that the recovery of neglect and of the activities of daily living was accelerated only in cTBS responders. Furthermore, the level of activities of daily living recovery of these neglect patients was brought close to the one of right-hemispheric control patients without neglect. Hence, in neglect patients with intact interhemispheric connectivity, cTBS over the contralesional posterior parietal cortex significantly improves and accelerates neglect recovery and, associated with it, general functional outcome.

Development of Right-hemispheric Dominance of Inferior Parietal Lobule in Proprioceptive Illusion Task.

Functional lateralization can be an indicator of brain maturation. We have consistently shown that, in the adult brain, proprioceptive processing of muscle spindle afferents generating illusory movement of the right hand activates inferior frontoparietal cortical regions in a right-side dominant manner in addition to the cerebrocerebellar motor network. Here we provide novel evidence regarding the development of the right-dominant use of the inferior frontoparietal cortical regions in humans using this task. We studied brain activity using functional magnetic resonance imaging while 60 right-handed blindfolded healthy children (8-11 years), adolescents (12-15 years), and young adults (18-23 years) (20 per group) experienced the illusion. Adult-like right-dominant use of the inferior parietal lobule (IPL) was observed in adolescents, while children used the IPL bilaterally. In contrast, adult-like lateralized cerebrocerebellar motor activation patterns were already observable in children. The right-side dominance progresses during adolescence along with the suppression of the left-sided IPL activity that emerges during childhood. Therefore, the neuronal processing implemented in the adult's right IPL during the proprioceptive illusion task is likely mediated bilaterally during childhood, and then becomes right-lateralized during adolescence at a substantially later time than the lateralized use of the cerebrocerebellar motor system for kinesthetic processing.

High spirituality may be associated with right hemispheric lateralization in Korean adults living with epilepsy.

PURPOSE: Although it is known that epilepsy and spirituality are related, spirituality in epilepsy has received relatively little clinical and scientific attention. Therefore, we investigated which epilepsy-related factors are associated with high spirituality in Korean adults living with epilepsy. METHODS: This cross-sectional study was conducted in two university hospitals in Korea. Spirituality was assessed using the 6-item Spirituality Self-Rating Scale (SSRS). The participants were categorized into high and low spirituality groups according to the median SSRS score. The presumptive seizure onset zone was determined based on the clinical semiology, electroencephalography, and magnetic resonance imaging findings. RESULTS: Of the 180 participants, 61.7% declared that they had a religious affiliation. The median SSRS score was 15 (interquartile range: 7, 22). The high spirituality subgroup consisted of 92 (51.1%) participants. In the univariate analyses, the high spirituality group was significantly associated with female sex (p<0.05), older age (p<0.01), longer epilepsy duration (p<0.05), polytherapy (p<0.05), complex partial seizure (p<0.05), levetiracetam or topiramate usage (p<0.05), and a right-lateralized seizure onset zone. The multiple logistic regression analysis identified right hemispheric lateralization as the only independent factor associated with high spirituality (odds ratio: 2.410, 95% confidence interval: 1.051-5.528, p<0.05). CONCLUSIONS: High spirituality may be associated with right hemispheric lateralization but not with the temporal localization of the seizure onset zone in Korean adults with epilepsy.

Some historical notes orienting towards brain mechanisms that could underlie hemispheric asymmetries.

The first minor aim of this synthetical historical survey consisted in showing that the discovery of the internal organization of language within the left hemisphere has been mainly determined by theoretical models and cultural factors, whereas the discovery of the left lateralisation of language and of the right lateralization of emotions and of other cognitive and perceptual functions has been mainly determined by empirical observations. A second more relevant aim of the survey consisted in discussing historical and more recent data suggesting that the different lateralisation of language and emotions has influenced not only the asymmetrical representation of other cognitive, affective and perceptual functions, but also (thank to the shaping influence of language on human cognition) of asymmetries regarding more general aspects of thought (such as the distinctions between 'propositional vs automatic' and 'conscious vs unconscious' ways of functioning). In the last part of the review, these data will be included in a more general discussion, concerning the brain functions that could be subsumed by the right hemisphere for three main reasons: (a) to avoid conflicts with the language mediated activities of the left hemisphere; (b) because of unconscious and automatic aspects of its non-verbal organisation or (c) due to the competition for cortical space determined by the development of language within the left hemisphere.

Clinimetric properties of relevant criteria for assessing writing and drawing orientation after right hemisphere stroke.

BACKGROUND: Writing and drawing orientation is rarely assessed in clinical routine, although it might have a potential value in detecting impaired verticality perception after right hemispheric stroke (RHS). Assessment tools and criteria must be conceived and validated. We therefore explored the clinimetric properties of a set of quantitative writing and drawing orientation criteria, their ranges of normality, and their tilt prevalence in RHS individuals. NEW METHODS: We asked 69 individuals with subacute RHS and 64 matched healthy controls to write three lines and to copy the Gainotti Figure (house and trees). We determined six criteria referring to the orientation of writing and drawing main axes: for writing, the line and margin orientations, and for drawing, the tree, groundline, wall, and roofline orientations. Orientations were measured by using an electronic protractor from specific landmarks positioned by independent evaluators. RESULTS: The set of criteria fulfilling all clinimetric properties (feasibility, measurability, reliability) comprised the line orientation of the writing and the wall and roofline orientations of the drawing. Writing and drawing tilts were frequent after RHS (about 30% by criterion). COMPARISON WITH EXISTING METHODS: So far, graphomotor orientation was mostly tested qualitatively and could not be objectively appreciated in absence of validated tools and criteria, and without ranges of normality. Writing and drawing tilts may now be assessed both in routine clinical practice and research. CONCLUSIONS: Our study paves the way for investigating the clinical determinants of graphomotor tilts, including impaired verticality perception, to better understand their underlying mechanisms.

Does Right-Hemispheric Anodal tDCS Enhance the Impact of Script Training in Chronic Aphasia? A Single-Subject Experimental Study.

Background: Script training is an aphasia treatment approach that has been demonstrated to have a positive effect on communication of individuals with aphasia; however, it is time intensive as a therapeutic modality. To augment therapy-induced neuroplasticity, transcranial direct current stimulation (tDCS) may be implemented. tDCS has been paired with other speech-language treatments, however, has not been investigated with script training. Aims: The purpose of this study was to determine if tDCS improves communication proficiency when paired with script training, compared to script training alone. Methods and Procedures: A single-subject experimental design was implemented with a participant with non-fluent aphasia, using two scripts across treatment conditions: script training with sham-tDCS, and script training with anodal-tDCS. Treatment sessions were 75 min long, administered three times weekly. Anodal tDCS was implemented for 20 min with a current of 1.5 mA over the right inferior frontal gyrus. Results: Large effect sizes were obtained on script mastery for both stimulation conditions (anodal d 2 = 9.94; sham d 2 = 11.93). tDCS did not improve script accuracy, however, there was a significant improvement in the rate of change of script pace relative to baseline (3.99 seconds/day, p < 0.001) in the anodal tDCS condition. Conclusion: Despite a null tDCS result on accuracy, the script training protocol increased script performance to a near-fluent level of communication. There is preliminary evidence to suggest that tDCS may alter the rate of script acquisition, however, further research to corroborate this finding is required. Implications for future studies are discussed.

Eyetracking during free visual exploration detects neglect more reliably than paper-pencil tests.

Neglect after stroke is most accurately diagnosed by a systematic, ecological observation during everyday behaviour using the Catherine Bergego Scale (CBS). However, the CBS is time-consuming and often omitted in clinical settings, especially stroke units. In this study, we aimed to explore if video-oculography during free visual exploration (FVE), which can be performed in few minutes, is sensitive in mirroring neglect in everyday behaviour and whether it is more sensitive than conventional neuropsychological paper-pencil tests. In this retrospective, observational, multicentre study, we identified 78 patients in our database with subacute right-hemispheric stroke, with and without neglect in everyday behaviour, diagnosed by the CBS, who also performed FVE. 40 age-matched healthy participants served as controls. The sensitivity to detect neglect was compared between FVE (i.e., mean gaze position on the horizontal axis) and conventional neuropsychological paper-pencil tests, i.e., Random Shape Cancellation, Line Bisection, Two-Part Picture, Bells, Star Cancellation, Letter Cancellation, Sensitive Neglect, and Five-Point. FVE correctly identified neglect in 85%of patients, with an AUC-value of .922 in ROC-analysis. Conventional neuropsychological paper-pencil tests, considered alone or in combination, showed heterogeneous results, and identified neglect significantly less often (21.74%-68.75%). Moreover, there was a significant correlation between mean gaze position and CBS scores, providing evidence for the relationship between FVE and neglect in everyday behaviour. Furthermore, VLSM analyses suggested that the absence of a pathological rightward bias in FVE might depend on the integrity of the second branch of the right Superior Longitudinal Fascicle (SLF II), a white-matter tract connecting cortical areas critical for visual attention. Video-oculography during FVE has a high sensitivity and specificity to diagnose neglect after stroke and it is more sensitive than conventional neuropsychological paper-pencil tests. It can be performed in short time and has the potential to be used as a fast and accurate screening tool that allows the initiation of comprehensive neuropsychological diagnostics and therapy from early on.

Right-hemispheric Dominance in Self-body Recognition is Altered in Left-handed Individuals.

Visual self-face and proprioceptive postural recognition predominantly activate the right inferior frontoparietal cortices in human right-handers at the population level. In the present study, prompted by the finding that left-handedness may alter lateralized cortical organization for language, sensory-motor, and cognitive functions observed in right-handers, we investigated individual variations in right-dominant use of the cortices in 50 right-handers and 50 left-handers during self-body recognition (self-face and proprioceptive) tasks. We also investigated possible between-tasks differences in this right-dominant use, and possible atypical left-right reversed lateralization (right-dominance for language and left-dominance for self-body recognition) in left-handers. We measured brain activity using functional magnetic resonance imaging while participants performed a proprioceptive postural recognition task (experiencing illusory movements of the left and the right hands), a visual self-face recognition (self-other distinction) task, and a language (verb generation) task. To evaluate hemispheric dominance, we computed individual lateralization indices for the inferior frontoparietal activities in these tasks. Left-handedness altered the right-hemispheric dominance that was observed in the majority of right-handed participants in both self-body recognition tasks. In the left-handed group, during proprioceptive recognition, participants with right-lateralization, bilaterality, or left-lateralization were equally distributed, and during self-face recognition, right-lateralization was still observed, though the number of participants who demonstrated left-lateralization increased. Atypical left-right reversed lateralization was only observed in left-handed participants, but during both self-body recognition tasks. The present study provides novel and valuable knowledge about right-hemispheric dominance in self-body recognition affected by left-handedness. We discuss how functional lateralization of self-body recognition is shaped in human brain, in terms of handedness, language lateralization, and development.

Reshaping the brain after stroke: The effect of prismatic adaptation in patients with right brain damage.

Prismatic adaptation has been repeatedly reported to alleviate neglect symptoms; in normal subjects, it was shown to enhance the representation of the left visual space within the left inferior parietal cortex. Our study aimed to determine in humans whether similar compensatory mechanisms underlie the beneficial effect of prismatic adaptation in neglect. Fifteen patients with right hemispheric lesions and 11 age-matched controls underwent a prismatic adaptation session which was preceded and followed by fMRI using a visual detection task. In patients, the prismatic adaptation session improved the accuracy of target detection in the left and central space and enhanced the representation of this visual space within the left hemisphere in parts of the temporal convexity, inferior parietal lobule and prefrontal cortex. Across patients, the increase in neuronal activation within the temporal regions correlated with performance improvements in this visual space. In control subjects, prismatic adaptation enhanced the representation of the left visual space within the left inferior parietal lobule and decreased it within the left temporal cortex. Thus, a brief exposure to prismatic adaptation enhances, both in patients and in control subjects, the competence of the left hemisphere for the left space, but the regions extended beyond the inferior parietal lobule to the temporal convexity in patients. These results suggest that the left hemisphere provides compensatory mechanisms in neglect by assuming the representation of the whole space within the ventral attentional system. The rapidity of the change suggests that the underlying mechanism relies on uncovering pre-existing synaptic connections.

Electrophysiological evidence for separation between human face and non-face object processing only in the right hemisphere.

Scalp event-related potential (ERP) studies have demonstrated larger N170 amplitudes when subjects view faces compared to items from object categories. Extensive attempts have been made to clarify face selectivity and hemispheric dominance for face processing. The purpose of this study was to investigate hemispheric differences in N170s activated by human faces and non-face objects, as well as the extent of overlap of their sources. ERP was recorded from 20 subjects while they viewed human face and non-face images. N170s obtained during the presentation of human faces appeared earlier and with larger amplitude than for other category images. Further source analysis with a two-dipole model revealed that the locations of face and object processing largely overlapped in the left hemisphere. Conversely, the source for face processing in the right hemisphere located more anterior than the source for object processing. The results suggest that the neuronal circuits for face and object processing are largely shared in the left hemisphere, with more distinct circuits in the right hemisphere.

Dorsal and Ventral Pathways for Prosody.

Our vocal tone--the prosody--contributes a lot to the meaning of speech beyond the actual words. Indeed, the hesitant tone of a "yes" may be more telling than its affirmative lexical meaning. The human brain contains dorsal and ventral processing streams in the left hemisphere that underlie core linguistic abilities such as phonology, syntax, and semantics. Whether or not prosody--a reportedly right-hemispheric faculty--involves analogous processing streams is a matter of debate. Functional connectivity studies on prosody leave no doubt about the existence of such streams, but opinions diverge on whether information travels along dorsal or ventral pathways. Here we show, with a novel paradigm using audio morphing combined with multimodal neuroimaging and brain stimulation, that prosody perception takes dual routes along dorsal and ventral pathways in the right hemisphere. In experiment 1, categorization of speech stimuli that gradually varied in their prosodic pitch contour (between statement and question) involved (1) an auditory ventral pathway along the superior temporal lobe and (2) auditory-motor dorsal pathways connecting posterior temporal and inferior frontal/premotor areas. In experiment 2, inhibitory stimulation of right premotor cortex as a key node of the dorsal stream decreased participants' performance in prosody categorization, arguing for a motor involvement in prosody perception. These data draw a dual-stream picture of prosodic processing that parallels the established left-hemispheric multi-stream architecture of language, but with relative rightward asymmetry.

Individual differences in hemispheric preference and emotion regulation difficulties.

BACKGROUND: Hemisphericity or individual difference in the preference to use the left or the right hemispheric mode of information processing has been associated with various emotion-related differences. For example, the right hemisphericity has been linked with inhibition of emotional expression, feeling of tension, greater impulsivity etc. These observations suggest that right hemisphericity may be associated with greater difficulties in regulating emotions. However, direct empirical tests of such theoretical proposition are very thin. AIM: In view of this, the present study aims to investigate how and to what extent individual difference in hemispheric preference relate to emotion regulation. MATERIALS AND METHODS: Thirty-two right-handed male subjects in the age range 18 to 20 years were assessed on self-report measures of hemispheric preference and emotion regulation difficulties. The correlation between dimensions of hemispheric preference and difficulties in regulating emotions was computed. A series of stepwise multiple regression analyses were also done to explore the relative significance of various dimensions of hemispheric preference in predicting emotion regulation difficulties. RESULTS: The findings revealed that in general a preference for the right hemispheric mode of information processing was associated with greater emotion regulation difficulties. The correlation analysis indicated that while impulse control difficulties and difficulties in engaging goal directed behavior was associated with preference for almost all the right hemispheric mode of information processing, the nonacceptance of emotional responses and limited access to emotion regulation was related to preference for only global/synthetic (a right hemispheric) mode of information processing. Similarly, the lack of emotional clarity facet of emotion regulation difficulties correlated significantly with a preference for the emotional mode of information processing (again a right hemispheric mode). The results of stepwise multiple regression analyses, however, indicated that "nonacceptance of emotional responses' and 'limited access to emotion regulation strategies" facets of emotion regulation difficulties were best predicted by a preference for the global/synthetic mode of information processing. While others like difficulties engaging in goal-directed behaviour, impulse control difficulties, and lack of emotional clarity were best predicted by a preference for visuo-spatial rather than the verbal mode of information processing. CONCLUSION: Overall, the findings imply that greater preference for right hemispheric mode of information processing as compared to the left is associated with greater difficulties in regulating emotions.