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.

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.

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.

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.

Structural Organization of the Corpus Callosum Predicts Attentional Shifts after Continuous Theta Burst Stimulation.

Repetitive transcranial magnetic stimulation (rTMS) applied over the right posterior parietal cortex (PPC) in healthy participants has been shown to trigger a significant rightward shift in the spatial allocation of visual attention, temporarily mimicking spatial deficits observed in neglect. In contrast, rTMS applied over the left PPC triggers a weaker or null attentional shift. However, large interindividual differences in responses to rTMS have been reported. Studies measuring changes in brain activation suggest that the effects of rTMS may depend on both interhemispheric and intrahemispheric interactions between cortical loci controlling visual attention. Here, we investigated whether variability in the structural organization of human white matter pathways subserving visual attention, as assessed by diffusion magnetic resonance imaging and tractography, could explain interindividual differences in the effects of rTMS. Most participants showed a rightward shift in the allocation of spatial attention after rTMS over the right intraparietal sulcus (IPS), but the size of this effect varied largely across participants. Conversely, rTMS over the left IPS resulted in strikingly opposed individual responses, with some participants responding with rightward and some with leftward attentional shifts. We demonstrate that microstructural and macrostructural variability within the corpus callosum, consistent with differential effects on cross-hemispheric interactions, predicts both the extent and the direction of the response to rTMS. Together, our findings suggest that the corpus callosum may have a dual inhibitory and excitatory function in maintaining the interhemispheric dynamics that underlie the allocation of spatial attention. SIGNIFICANCE STATEMENT: The posterior parietal cortex (PPC) controls allocation of attention across left versus right visual fields. Damage to this area results in neglect, characterized by a lack of spatial awareness of the side of space contralateral to the brain injury. Transcranial magnetic stimulation over the PPC is used to study cognitive mechanisms of spatial attention and to examine the potential of this technique to treat neglect. However, large individual differences in behavioral responses to stimulation have been reported. We demonstrate that the variability in the structural organization of the corpus callosum accounts for these differences. Our findings suggest novel dual mechanism of the corpus callosum function in spatial attention and have broader implications for the use of stimulation in neglect rehabilitation.

Structural Variability within Frontoparietal Networks and Individual Differences in Attentional Functions: An Approach Using the Theory of Visual Attention.

Visuospatial attention allows us to select and act upon a subset of behaviorally relevant visual stimuli while ignoring distraction. Bundesen's theory of visual attention (TVA) (Bundesen, 1990) offers a quantitative analysis of the different facets of attention within a unitary model and provides a powerful analytic framework for understanding individual differences in attentional functions. Visuospatial attention is contingent upon large networks, distributed across both hemispheres, consisting of several cortical areas interconnected by long-association frontoparietal pathways, including three branches of the superior longitudinal fasciculus (SLF I-III) and the inferior fronto-occipital fasciculus (IFOF). Here we examine whether structural variability within human frontoparietal networks mediates differences in attention abilities as assessed by the TVA. Structural measures were based on spherical deconvolution and tractography-derived indices of tract volume and hindrance-modulated orientational anisotropy (HMOA). Individual differences in visual short-term memory (VSTM) were linked to variability in the microstructure (HMOA) of SLF II, SLF III, and IFOF within the right hemisphere. Moreover, VSTM and speed of information processing were linked to hemispheric lateralization within the IFOF. Differences in spatial bias were mediated by both variability in microstructure and volume of the right SLF II. Our data indicate that the microstructural and macrostrucutral organization of white matter pathways differentially contributes to both the anatomical lateralization of frontoparietal attentional networks and to individual differences in attentional functions. We conclude that individual differences in VSTM capacity, processing speed, and spatial bias, as assessed by TVA, link to variability in structural organization within frontoparietal pathways.

Lesion-symptom mapping of self-prioritization in explicit face categorization: distinguishing hypo- and hyper-self-biases.

People make faster familiarity decisions for their own face compared with a familiar other. Lesion studies diverge on whether this self-face prioritization (SFP) effect is associated with functional processes isolated in the left or right hemispheres. To assess both decreases (hypo-) and increases (hyper-) in SFP after brain lesion, we asked patients with chronic deficits to perform familiarity judgments to images of their own face, a familiar other, or unfamiliar faces. Of 30 patients, 7 showed hypo- and 6 showed hyper-self-bias effects, comparing responses with their own faces versus responses with a familiar other. Hyper-self-bias correlated with reduced executive control function and, at a neural level, this was associated with lesions to the left prefrontal and superior temporal cortices. In contrast, reduced self-prioritization was associated with damage to the right inferior temporal structures including the hippocampus and extending to the fusiform gyrus. In addition, lesions affecting fibers crossing the right temporal cortex, potentially disconnecting occipital-temporal from frontal regions, diminished the self-bias effect. The data highlight that self-prioritized face processing is linked to regions in the right hemisphere associated with face recognition memory and it also calls on executive processes in the left hemisphere that normally modulate self-prioritized attention.

A Neural Decomposition of Visual Search Using Voxel-based Morphometry.

The ability to search efficiently for visual targets among distractors can break down after a variety of brain lesions, but the specific processes affected by the lesions are unclear. We examined search over space (conjunction search) and over time plus space (preview search) in a consecutive series of patients with acquired brain lesions. We also assessed performance on standard neuropsychological measures of visuospatial short-term memory (Corsi Block), sustained attention and memory updating (the contrast between forward and backward digit span), and visual neglect. Voxel-based morphometry analyses revealed regions in the occipital (middle occipital gyrus), posterior parietal (angular gyrus), and temporal cortices (superior and middle temporal gyri extending to the insula), along with underlying white matter pathways, associated with poor search. Going beyond standard voxel-based morphometry analyses, we then report correlation measures of structural damage in these regions and the independent neuropsychological measures of other cognitive functions. We find distinct patterns of correlation in areas linked to poor search, suggesting that the areas play functionally different roles in search. We conclude that neuropsychological disorders of search can be linked to necessary and distinct cognitive functions, according to the site of lesion.

Examining evidence for behavioural mimicry of parental eating by adolescent females. An observational study.

Behavioural mimicry is a potential mechanism explaining why adolescents appear to be influenced by their parents' eating behaviour. In the current study we examined whether there is evidence that adolescent females mimic their parents when eating. Videos of thirty-eight parent and female adolescent dyads eating a lunchtime meal together were examined. We tested whether a parent placing a food item into their mouth was associated with an increased likelihood that their adolescent child would place any food item (non-specific mimicry) or the same item (specific mimicry) in their mouth at three different time frames, namely, during the same second or within the next fifteen seconds (+15), five seconds (+5) or two second (+2) period. Parents and adolescents' overall food intake was positively correlated, whereby a parent eating a larger amount of food was associated with the adolescent eating a larger meal. Across all of the three time frames adolescents were more likely to place a food item in their mouth if their parent had recently placed that same food item in their mouth (specific food item mimicry); however, there was no evidence of non-specific mimicry. This observational study suggests that when eating in a social context there is evidence that adolescent females may mimic their parental eating behaviour, selecting and eating more of a food item if their parent has just started to eat that food.

The neural substrates of drawing: a voxel-based morphometry analysis of constructional, hierarchical, and spatial representation deficits.

Deficits in the ability to draw objects, despite apparently intact perception and motor abilities, are defined as constructional apraxia. Constructional deficits, often diagnosed based on performance on copying complex figures, have been reported in a range of pathologies, perhaps reflecting the contribution of several underlying factors to poor figure drawing. The current study provides a comprehensive analysis of brain-behavior relationships in drawing disorders based on data from a large cohort of subacute stroke patients (n = 358) using whole-brain voxel-wise statistical analyses linked to behavioral measures from a complex figure copy task. We found that (i) overall poor performance on figure copying was associated with subcortical lesions (BG and thalamus), (ii) lateralized deficits with respect to the midline of the viewer were associated with lesions within the posterior parietal lobule, and (iii) spatial positioning errors across the entire figure were associated with lesions within visual processing areas (lingual gyrus and calcarine) and the insula. Furthermore, deficits in reproducing global aspects of form were associated with damage to the right middle temporal gyrus, whereas deficits in representing local features were linked to the left hemisphere lesions within calcarine cortex (extending into the cuneus and precuneus), the insula, and the TPJ. The current study provides strong evidence that impairments in separate cognitive mechanisms (e.g., spatial coding, attention, motor execution, and planning) linked to different brain lesions contribute to poor performance on complex figure copying tasks. The data support the argument that drawing depends on several cognitive processes operating via discrete neuronal networks and that constructional problems as well as hierarchical and spatial representation deficits contribute to poor figure copying.

The structural and functional connectivity of the posterior cingulate cortex: comparison between deterministic and probabilistic tractography for the investigation of structure-function relationships.

The default mode network (DMN) is one of the most studied resting-state networks, and is thought to be involved in the maintenance of consciousness within the alert human brain. Although many studies have examined the functional connectivity (FC) of the DMN, few have investigated its underlying structural connectivity (SC), or the relationship between the two. We investigated this question in fifteen healthy subjects, concentrating on connections to the precuneus/posterior cingulate cortex (PCC), commonly considered as the central node of the DMN. We used group independent component analysis (GICA) and seed-based correlation analysis of fMRI data to quantify FC, and streamline and probabilistic tractography to identify structural tracts from diffusion tensor imaging (DTI) data. We first assessed the presence of structural connections between the DMN regions identified with GICA. Of the 15 subjects, when using the probabilistic approach 15 (15) demonstrated connections between the PCC and mesial prefrontal cortex (mPFC), 11 (15) showed connections from the PCC to the right inferior parietal cortex (rIPC) and 8 (15) to the left IPC. Next, we assessed the strength of FC (magnitude of temporal correlation) and SC (mean fractional anisotropy of reconstructed tracts (streamline), number of super-threshold voxels within the mask region (probabilistic)). The lIPC had significantly reduced FC to the PCC compared to the mPFC and rIPC. No difference in SC strength between connections was found using the streamline approach. For the probabilistic approach, mPFC had significantly lower SC than both IPCs. The two measures of SC strength were significantly correlated, but not for all paired connections. Finally, we observed a significant correlation between SC and FC for both tractography approaches when data were pooled across PCC-lIPL, PCC-rIPL and PCC-mPFC connections, and for some individual paired connections. Our results suggest that the streamline approach is advantageous for characterising the connectivity of long white matter tracts (PCC-mPFC), whilst the probabilistic approach was more reliable at identifying PCC-IPC connections. The direct comparison of FC and SC indicated that pairs of nodes with stronger structural connections also had stronger functional connectivity, and that this was maintained with both tractography approaches. Whilst the definition of SC strength remains controversial, our results could be considered to provide some degree of validation for the measures of SC strength that we have used. Direct comparisons of SC and FC are necessary in order to understand the structural basis of functional connectivity, and to characterise and quantify the changes in the brain's functional architecture that occur as a result of normal physiology or pathology.

Parietal substrates for dimensional effects in visual search: evidence from lesion-symptom mapping.

In visual search, the detection of pop-out targets is facilitated when the target-defining dimension remains the same compared with when it changes across trials. We tested the brain regions necessary for these dimensional carry-over effects using a voxel-based morphometry study with brain-lesioned patients. Participants had to search for targets defined by either their colour (red or blue) or orientation (right- or left-tilted), and the target dimension either stayed the same or changed on consecutive trials. Twenty-five patients were categorized according to whether they showed an effect of dimensional change on search or not. The two groups did not differ with regard to their performance on several working memory tasks, and the dimensional carry-over effects were not correlated with working memory performance. With spatial, sustained attention and working memory deficits as well as lesion volume controlled, damage within the right inferior parietal lobule (the angular and supramarginal gyri) extending into the intraparietal sulcus was associated with an absence of dimensional carry-over (P < 0.001, cluster-level corrected for multiple comparisons). The data suggest that these regions of parietal cortex are necessary to implement attention shifting in the context of visual dimensional change.

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.

The neural underpinings of simultanagnosia: disconnecting the visuospatial attention network.

Because of our limited processing capacity, different elements of the visual scene compete for the allocation of processing resources. One of the most striking deficits in visual selection is simultanagnosia, a rare neuropsychological condition characterized by impaired spatial awareness of more than one object at time. To decompose the neuroanatomical substrates of the syndrome and to gain insights into the structural and functional organization of visuospatial attention, we performed a systematic evaluation of lesion patterns in a group of simultanagnosic patients compared with patients with either (i) unilateral visuospatial deficits (neglect and/or extinction) or (ii) bilateral posterior lesions without visuospatial deficits, using overlap/subtraction analyses, estimation of lesion volume, and a lesion laterality index. We next used voxel-based morphometry to assess the link between different visuospatial deficits and gray matter and white matter (WM) damage. Lesion overlap/subtraction analyses, lesion laterality index, and voxel-based morphometry measures converged to indicate that bilateral parieto-occipital WM disconnections are both distinctive and necessary to create symptoms associated with simultanagnosia. We also found that bilateral gray matter damage within the middle frontal area (BA 46), cuneus, calacarine, and parieto-occipital fissure as well as right hemisphere parietal lesions within intraparietal and postcentral gyri were associated with simultanagnosia. Further analysis of the WM based on tractography revealed associations with bilateral damage to major pathways within the visuospatial attention network, including the superior longitudinal fasciculus, the inferior fronto-occipital fasciculus, and the inferior longitudinal fasciculus. We conclude that damage to the parieto-occipital regions and the intraparietal sulcus, together, with bilateral WM disconnections within the visuosptial attention network, contribute to poor visual processing of multiple objects and the loss of processing speed characteristic of simultanagnosia.

Spatial and temporal attention deficits following brain injury: a neuroanatomical decomposition of the temporal order judgement task.

We investigated spatial and temporal deficits following brain injury using the temporal order judgement (TOJ) task. Patients judged the order in which two letters appeared to the left and right of fixation. We measured the extent of any spatial bias and the temporal resolution of the decision. Temporal and spatial deficits on the TOJ task were significantly correlated. The spatial bias on the TOJ task was also correlated with the spatial bias on a neglect task and with unilateral deficits on an extinction task, but not with extinction itself. These spatial deficits were all associated with damage to contralateral temporoparietal cortex. In contrast, the temporal resolution of TOJs was linked specifically to deficits in processing multiple stimuli on the neglect and extinction tasks and to damage to the right parietal lobe and the cerebellum. These data suggest that spatial and temporal deficits on the TOJ task reflect different underlying processes.

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.

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.

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.

Separating neural correlates of allocentric and egocentric neglect: distinct cortical sites and common white matter disconnections.

Insights into the functional nature and neuroanatomy of spatial attention have come from research in neglect patients but to date many conflicting results have been reported. The novelty of the current study is that we used voxel-wise analyses based on information from segmented grey and white matter tissue combined with diffusion tensor imaging to decompose neural substrates of different neglect symptoms. Allocentric neglect was associated with damage to posterior cortical regions (posterior superior temporal sulcus, angular, middle temporal and middle occipital gyri). In contrast, egocentric neglect was associated with more anterior cortical damage (middle frontal, postcentral, supramarginal, and superior temporal gyri) and damage within subcortical structures. Damage to intraparietal sulcus (IPS) and the temporo-parietal junction (TPJ) was associated with both forms of neglect. Importantly, we showed that both disorders were associated with white matter lesions suggesting damage within long association and projection pathways such as the superior longitudinal, superior fronto-occipital, inferior longitudinal, and inferior fronto-occipital fascicule, thalamic radiation, and corona radiata. We conclude that distinct cortical regions control attention (a) across space (using an egocentric frame of reference) and (b) within objects (using an allocentric frame of reference), while common cortical regions (TPJ, IPS) and common white matter pathways support interactions across the different cortical regions.