Causal Roles of Ventral and Dorsal Neural Systems for Automatic and Control Self-Reference Processing: A Function Lesion Mapping Study.

Background: Humans perceive and interpret the world through the lens of self-reference processes, typically facilitating enhanced performance for the task at hand. However, this research has predominantly emphasized the automatic facet of self-reference processing, overlooking how it interacts with control processes affecting everyday situations. Methods: We investigated this relationship between automatic and control self-reference processing in neuropsychological patients performing self-face perception tasks and the Birmingham frontal task measuring executive functions. Results: Principal component analysis across tasks revealed two components: one loaded on familiarity/orientation judgments reflecting automatic self-reference processing, and the other linked to the cross task and executive function indicating control processing requirements. Voxel-based morphometry and track-wise lesion-mapping analyses showed that impairments in automatic self-reference were associated with reduced grey matter in the ventromedial prefrontal cortex and right inferior temporal gyrus, and white matter damage in the right inferior fronto-occipital fasciculus. Deficits in executive control were linked to reduced grey matter in the bilateral inferior parietal lobule and left anterior insula, and white matter disconnections in the left superior longitudinal fasciculus and arcuate fasciculus. Conclusions: The causal evidence suggests that automatic and control facets of self-reference processes are subserved by distinct yet integrated ventral prefrontal-temporal and dorsal frontal-parietal networks, respectively.

Right fronto-parietal networks mediate the neurocognitive benefits of enriched environments.

Exposure to enriched environments throughout a lifetime, providing so-called reserve, protects against cognitive decline in later years. It has been hypothesized that high levels of alertness necessitated by enriched environments might strengthen the right fronto-parietal networks to facilitate this neurocognitive resilience. We have previously shown that enriched environments offset age-related deficits in selective attention by preserving grey matter within right fronto-parietal regions. Here, using neurite orientation dispersion and density imaging, we examined the relationship between enriched environments, microstructural properties of fronto-parietal white matter association pathways (three branches of the superior longitudinal fasciculus), structural brain health (atrophy), and attention (alertness, orienting and executive control) in a group of older adults. We show that exposure to enriched environments is associated with a lower orientation dispersion index within the right superior longitudinal fasciculus 1 which in turn mediates the relationship between enriched environments and alertness, as well as grey and white matter atrophy. This suggests that enriched environments may induce white matter plasticity (and prevent age-related dispersion of axons) within the right fronto-parietal networks to facilitate the preservation of neurocognitive health in later years.

The association between inadequate sleep and accelerated brain ageing.

Numerous studies indicate large heterogeneity in brain ageing, which can be attributed to modifiable lifestyle factors, including sleep. Inadequate sleep has been previously linked to gray (GM) and white (WM) matter changes. However, the reported findings are highly inconsistent. By contrast to previous research independently characterizing patterns of either GM or WM changes, we used here linked independent component analysis (FLICA) to examine covariation in GM, and WM in a group of older adults (n = 50). Next, we employed a novel technique to estimate the brain age delta (difference between chronological and brain age assessed using neuroimaging data) and study its associations with sleep quality and sleep fragmentation, hypothesizing that inadequate sleep accelerates brain ageing. FLICA revealed a number of multimodal components, associated with age, sleep quality, and sleep fragmentation. Subsequently, we show significant associations between brain age delta and inadequate sleep, suggesting 2 years deviation above the chronological age. Our findings indicate sensitivity of multimodal approaches and brain age delta in detecting link between inadequate sleep and accelerated brain ageing.

The role of the parietal cortex in inhibitory processing in the vertical meridian: Evidence from elderly brain damaged patients.

We explored the effects of parietal damage on inhibitory effects of visuospatial attention, inhibition of return (IOR) and inhibitory tagging (IT), in the vertical meridian. We combined a vertical spatial cue paradigm with a Stroop task employing three different temporal intervals between the spatial cue and the target (700, 1200 and 2000 ms) in two groups of patients, one with damage to the parietal cortex and underlying white matter (the parietal patients group) and the other with damage in other brain areas not including the parietal lobe (the control patient group), and a healthy control group. Healthy controls showed the expected inhibitory effects, IOR at the 700 and 1200 intervals and IT at the 1200 interval (as evidenced in a reduction in the magnitude of Stroop interference at the cued location). On the other hand, only the group of parietal patients showed delayed onset of inhibitory effects, IOR and IT appeared at the 1200 ms and 2000 ms intervals, respectively. These findings provide evidence for a role of the parietal cortex, and the underlying fibre tracts, in inhibitory processing in the vertical meridian, with damage to the parietal cortex altering the time course of attention-dependent inhibition.

SLC25A24 gene methylation and gray matter volume in females with and without conduct disorder: an exploratory epigenetic neuroimaging study.

Conduct disorder (CD), a psychiatric disorder characterized by a repetitive pattern of antisocial behaviors, results from a complex interplay between genetic and environmental factors. The clinical presentation of CD varies both according to the individual's sex and level of callous-unemotional (CU) traits, but it remains unclear how genetic and environmental factors interact at the molecular level to produce these differences. Emerging evidence in males implicates methylation of genes associated with socio-affective processes. Here, we combined an epigenome-wide association study with structural neuroimaging in 51 females with CD and 59 typically developing (TD) females to examine DNA methylation in relation to CD, CU traits, and gray matter volume (GMV). We demonstrate an inverse pattern of correlation between CU traits and methylation of a chromosome 1 region in CD females (positive) as compared to TD females (negative). The identified region spans exon 1 of the SLC25A24 gene, central to energy metabolism due to its role in mitochondrial function. Increased SLC25A24 methylation was also related to lower GMV in multiple brain regions in the overall cohort. These included the superior frontal gyrus, prefrontal cortex, and supramarginal gyrus, secondary visual cortex and ventral posterior cingulate cortex, which are regions that have previously been implicated in CD and CU traits. While our findings are preliminary and need to be replicated in larger samples, they provide novel evidence that CU traits in females are associated with methylation levels in a fundamentally different way in CD and TD, which in turn may relate to observable variations in GMV across the brain.

Right Lateralized Brain Reserve Offsets Age-Related Deficits in Ignoring Distraction.

Age-related deterioration of attention decreases the ability to stay focused on the task at hand due to less efficient selection of relevant information and increased distractibility in the face of irrelevant, but salient stimuli. While older (compared with younger) adults may have difficulty suppressing salient distractors, the extent of these challenges differs vastly across individuals. Cognitive reserve measured by proxies of cognitively enriching life experiences, such as education, occupation, and leisure activities, is thought to mitigate the effects of the aging process and account for variability in trajectories of cognitive decline. Based on combined behavioral and neuroimaging (voxel-based morphometry) analyses of demographic, cognitive, and neural markers of aging and cognitive reserve proxy measures, we examine here predictors of variability in the age-related changes in attention function, indexed by ability to suppress salient distraction. Our findings indicate that in healthy (neurotypical), aging gray matter volume within several right lateralized fronto-parietal brain regions varies according to both levels of cognitive reserve (education) and the capacity to effectively select visual stimuli amid salient distraction. Thus, we provide here novel experimental evidence supporting Robertson's theory of a right lateralized neural basis for cognitive reserve.

Dissociable Catecholaminergic Modulation of Visual Attention: Differential Effects of Catechol-O-Methyltransferase and Dopamine Beta-Hydroxylase Genes on Visual Attention.

Visual attention enables us to prioritise behaviourally relevant visual information while ignoring distraction. The neural networks supporting attention are modulated by two catecholamines, dopamine and noradrenaline. The current study investigated the effects of single nucleotide polymorphisms in two catecholaminergic genes - COMT (Val158Met) and DBH (444 G/A) - on individual differences in attention functions. Participants (n = 125) were recruited from the Oxford Biobank by genotype-based recall. They were tested on a continuous performance task (sustained attention), a Go/No-Go task (response inhibition), and a task assessing attentional selection in accordance with the Theory of Visual Attention (TVA). We found a significant effect of DBH genotype status on the capacity to maintain attention over time (sustained attention) as measured by the continuous performance task. Furthermore, we demonstrated a significant association between COMT genotype status and effective threshold of visual perception in attentional selection as estimated based on the TVA task performance. No other group differences in attention function were found with respect to the studied genotypes. Overall, our findings provide novel experimental evidence that: (i) dopaminergic and noradrenergic genotypes have dissociable effects on visual attention; (ii) either insufficient or excessive catecholaminergic activity may have equally detrimental effects on sustained attention.

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.

Bilateral parietal dysfunctions and disconnections in simultanagnosia and Bálint syndrome.

In 1909 Rezsö Bálint published an extraordinary case study of a man with complex visuospatial deficits resulting from bilateral parietal lesions. Despite some controversies over the nature of reported symptoms, in 1954 Hecaen and Ajuriaguerra conceived the term "Bálint syndrome," not only to honor Bálint's influential work but to firmly conceptualize this striking neurologic disorder. Nowadays it is largely agreed that, while Bálint syndrome may result from multiple etiologies, it is principally diagnosed based on the presence of three symptoms: simultanagnosia, optic ataxia, and ocular apraxia. One of the most striking characteristics of Bálint syndrome, perfectly capturing the nature of this remarkable disorder, is that affected patients cannot perceive more than one object at a time or comprehend multiobject visual scenes due to a lack of ability to detect several objects concurrently and to grasp the spatial relationships between them. This chapter gives an overview of the cognitive mechanisms and neuroanatomy underlying Bálint syndrome, which provides key insights into our understanding of the role of parietal cortex in human attention, visual perception, and visuomotor control. This chapter also pays homage to Glyn Humphreys (1954-2016), who pioneered contributions to the knowledge about complexity of visual and spatial deficits associated with Bálint syndrome.

Polarity-dependent Effects of Biparietal Transcranial Direct Current Stimulation on the Interplay between Target Location and Distractor Saliency in Visual Attention.

Visual attention allows the allocation of limited neural processing resources to stimuli based on their behavioral priorities. The selection of task-relevant visual targets entails the processing of multiple competing stimuli and the suppression of distractors that may be either perceptually salient or perceptually similar to targets. The posterior parietal cortex controls the interaction between top-down (task-driven) and bottom-up (stimulus-driven) processes competing for attentional selection, as well as spatial distribution of attention. Here, we examined whether biparietal transcranial direct current stimulation (tDCS) would modulate the interaction between top-down and bottom-up processes in visual attention. Visual attention function was assessed with a visual discrimination task, in which a lateralized target was presented alone or together with a contralateral, similar or salient, distractor. The accuracy and RTs were measured before and during three stimulation sessions (sham, right anodal/left cathodal, left anodal/right cathodal). The analyses demonstrated (i) polarity-dependent effects of tDCS on the accuracy of target discrimination, but only when the target was presented with a similar distractor; (ii) the tDCS-triggered effects on the accuracy of discriminating targets, accompanied by a similar distractor, varied according to the target location; and (iii) overall detrimental effects of tDCS on RTs were observed, regardless of target location, distractor type, and polarity of the stimulation. We conclude that the observed polarity, distractor type, and target location-dependent effects of biparietal tDCS on the accuracy of target detection resulted from both a modulation of the interaction between top-down and bottom-up attentional processes and the interhemispheric competition mechanisms guiding attentional selection and spatial deployment of attention.

Beyond time and space: The effect of a lateralized sustained attention task and brain stimulation on spatial and selective attention.

The Theory of Visual Attention (TVA) provides a mathematical formalisation of the "biased competition" account of visual attention. Applying this model to individual performance in a free recall task allows the estimation of 5 independent attentional parameters: visual short-term memory (VSTM) capacity, speed of information processing, perceptual threshold of visual detection; attentional weights representing spatial distribution of attention (spatial bias), and the top-down selectivity index. While the TVA focuses on selection in space, complementary accounts of attention describe how attention is maintained over time, and how temporal processes interact with selection. A growing body of evidence indicates that different facets of attention interact and share common neural substrates. The aim of the current study was to modulate a spatial attentional bias via transfer effects, based on a mechanistic understanding of the interplay between spatial, selective and temporal aspects of attention. Specifically, we examined here: (i) whether a single administration of a lateralized sustained attention task could prime spatial orienting and lead to transferable changes in attentional weights (assigned to the left vs right hemi-field) and/or other attentional parameters assessed within the framework of TVA (Experiment 1); (ii) whether the effects of such spatial-priming on TVA parameters could be further enhanced by bi-parietal high frequency transcranial random noise stimulation (tRNS) (Experiment 2). Our results demonstrate that spatial attentional bias, as assessed within the TVA framework, was primed by sustaining attention towards the right hemi-field, but this spatial-priming effect did not occur when sustaining attention towards the left. Furthermore, we show that bi-parietal high-frequency tRNS combined with the rightward spatial-priming resulted in an increased attentional selectivity. To conclude, we present a novel, theory-driven method for attentional modulation providing important insights into how the spatial and temporal processes in attention interact with attentional selection.

Microstructural abnormalities in white and gray matter in obese adolescents with and without type 2 diabetes.

AIMS/HYPOTHESES: In adults, type 2 diabetes and obesity have been associated with structural brain changes, even in the absence of dementia. Some evidence suggested similar changes in adolescents with type 2 diabetes but comparisons with a non-obese control group have been lacking. The aim of the current study was to examine differences in microstructure of gray and white matter between adolescents with type 2 diabetes, obese adolescents and healthy weight adolescents. METHODS: Magnetic resonance imaging data were collected from 15 adolescents with type 2 diabetes, 21 obese adolescents and 22 healthy weight controls. Volumetric differences in the gray matter between the three groups were examined using voxel based morphology, while tract based spatial statistics was used to examine differences in the microstructure of the white matter. RESULTS: Adolescents with type 2 diabetes and obese adolescents had reduced gray matter volume in the right hippocampus, left putamen and caudate, bilateral amygdala and left thalamus compared to healthy weight controls. Type 2 diabetes was also associated with significant regional changes in fractional anisotropy within the corpus callosum, fornix, left inferior fronto-occipital fasciculus, left uncinate, left internal and external capsule. Fractional anisotropy reductions within these tracts were explained by increased radial diffusivity, which may suggest demyelination of white matter tracts. Mean diffusivity and axial diffusivity did not differ between the groups. CONCLUSION/INTERPRETATION: Our data shows that adolescent obesity alone results in reduced gray matter volume and that adolescent type 2 diabetes is associated with both white and gray matter abnormalities.

The Neural Basis of Independence Versus Interdependence Orientations: A Voxel-Based Morphometric Analysis of Brain Volume.

Sociocultural research has established independence and interdependence as two fundamental ways of thinking about oneself and the social world. Recent neuroscience studies further demonstrate that these orientations modulate brain activity in various self- and socially related tasks. In the current study, we explored whether the traits of independence and interdependence are reflected in anatomical variations in brain structure. We carried out structural brain imaging on a large sample of healthy participants ( n = 265) who also completed self-report questionnaires of cultural orientations. Voxel-based morphometry analysis demonstrated that a relative focus of independence (vs. interdependence) was associated with increased gray-matter volume in a number of self-related regions, including ventromedial prefrontal cortex, right dorsolateral prefrontal cortex, and right rostrolateral prefrontal cortex. These results provide novel insights into the biological basis of sociocultural orientations.

A matter of hand: Causal links between hand dominance, structural organization of fronto-parietal attention networks, and variability in behavioural responses to transcranial magnetic stimulation.

Considerable evidence suggests that, on a group level, human visuospatial attention is asymmetrically organized, with a right-hemispheric dominance. The asymmetrical organization of the superior longitudinal fasciculus (SLF) has been shown to account for the right-hemispheric dominance in visual attention. However, such account is by no means universal, and large individual differences in asymmetrical performance on visuospatial tasks have been reported. Furthermore, the variability in the SLF lateralization has been shown to correlate with behavioural asymmetries. Continuous theta burst stimulation (cTBS) enables to temporarily interfere with cortical activity. cTBS applied over the posterior parietal cortex (PPC) has been previously used to systematically study attentional asymmetries. Interestingly, large individual differences in the effectiveness of stimulation have been reported. In accordance with earlier both animal and human studies, one possible cause underlying these striking individual differences might lie in the structural organization of frontoparietal pathways subserving visuospatial attention. Thus, the current study employed diffusion tractography to examine the relationship between the variability in the structural organization of the SLF and the individual differences in attentional shifts induced by a modified cTBS (cTBSmod; triplets of pulses at 30 Hz, repeated at 6 Hz) applied over the IPS, as measured by a line bisection task. Consistent with previous studies, on a group level, cTBSmod applied over the right intraparietal sulcus (IPS) triggered a rightward bisection bias shift, and there were no significant effects of cTBSmod applied over the left IPS. However, further analyses demonstrated that both handedness and structural variability (as assessed based on hindrance modulated orientational anisotropy) within the middle and the ventral branches of the SLF predicted individual differences in the cTBSmod-induced attentional shifts. Our study thus suggests that the effects of cTBSmod over the IPS may depend on intra-hemispheric interactions between cortical loci controlling visual attention. To conclude, our findings provide converging evidence for the notion put forward previously that inter-individual variability in the structural organization of intra-hemispheric frontoparietal connections has important implications for the functional models of human visual attention. Moreover, we hypothesize that this may also be relevant for the understanding of attentional disorders and their rehabilitation.

Relationship between Parental Feeding Practices and Neural Responses to Food Cues in Adolescents.

Social context, specifically within the family, influences adolescent eating behaviours and thus their health. Little is known about the specific mechanisms underlying the effects of parental feeding practices on eating. We explored relationships between parental feeding practices and adolescent eating habits and brain activity in response to viewing food images. Fifty- seven adolescents (15 with type 2 diabetes mellitus, 21 obese and 21 healthy weight controls) underwent fMRI scanning whilst viewing images of food or matched control images. Participants completed the Kids Child Feeding Questionnaire, the Childrens' Dutch Eating Behaviour Questionnaire (DEBQ) and took part in an observed meal. Parents completed the Comprehensive Feeding Practices Questionniare and the DEBQ. We were particularly interested in brain activity in response to food cues that was modulated by different feeding and eating styles. Healthy-weight participants increased activation (compared to the other groups) to food in proportion to the level of parental restriction in visual areas of the brain such as right lateral occipital cortex (LOC), right temporal occipital cortex, left occipital fusiform gyrus, left lateral and superior LOC. Adolescents with type 2 diabetes mellitus had higher activation (compared to the other groups) with increased parental restrictive feeding in areas relating to emotional control, attention and decision-making, such as posterior cingulate, precuneus, frontal operculum and right middle frontal gyrus. Participants with type 2 diabetes mellitus also showed higher activation (compared to the other groups) in the left anterior intraparietal sulcus and angular gyrus when they also reported higher self restraint. Parental restriction did not modulate food responses in obese participants, but there was increased activity in visual (visual cortex, left LOC, left occipital fusiform gyrus) and reward related brain areas (thalamus and parietal operculum) in response to parental teaching and modelling of behaviour. Parental restrictive feeding and parental teaching and modelling affected neural responses to food cues in different ways, depending on motivations and diagnoses, illustrating a social influence on neural responses to food cues.

Neural Mechanisms of Temporal Resolution of Attention.

The dynamic nature of the world requires that our visual representations are continuously updated. These representations are more precise if there is a narrow time window over which information is averaged. We assess the neural processes of visual updating by testing patients with lesions including inferior parietal cortex, control patients and healthy adults on a continuous visual monitoring task. In Experiment 1, observers kept track of the changing spatial period of a luminance grating and identified the final spatial period after the stimulus disappeared. Healthy older adults and neurological controls were able to perform better than simulated guesses, but only 3 of 11 patients with damage including parietal cortex were able to reach performance that differed from simulated guesses. The effects were unrelated to lesion size. Poor performance on this task is consistent with an inability to selectively attend to the final moment at which the stimulus was seen. To investigate the temporal limits of attention, we varied the rate of stimulus change in Experiment 2. Performance remained poor for some patients even with slow 2.5 Hz change rates. The performance of 4 patients with parietal damage displayed poor temporal precision, namely recovery of performance with slower rates of change.