Improving quantitative susceptibility mapping for the identification of traumatic brain injury neurodegeneration at the individual level.

BACKGROUND: Emerging evidence suggests that traumatic brain injury (TBI) is a major risk factor for developing neurodegenerative disease later in life. Quantitative susceptibility mapping (QSM) has been used by an increasing number of studies in investigations of pathophysiological changes in TBI. However, generating artefact-free quantitative susceptibility maps in brains with large focal lesions, as in the case of moderate-to-severe TBI (ms-TBI), is particularly challenging. To address this issue, we utilized a novel two-pass masking technique and reconstruction procedure (two-pass QSM) to generate quantitative susceptibility maps (QSMxT; Stewart et al., 2022, Magn Reson Med.) in combination with the recently developed virtual brain grafting (VBG) procedure for brain repair (Radwan et al., 2021, NeuroImage) to improve automated delineation of brain areas. We used QSMxT and VBG to generate personalised QSM profiles of individual patients with reference to a sample of healthy controls. METHODS: Chronic ms-TBI patients (N = 8) and healthy controls (N = 12) underwent (multi-echo) GRE, and anatomical MRI (MPRAGE) on a 3T Siemens PRISMA scanner. We reconstructed the magnetic susceptibility maps using two-pass QSM from QSMxT. We then extracted values of magnetic susceptibility in grey matter (GM) regions (following brain repair via VBG) across the whole brain and determined if they deviate from a reference healthy control group [Z-score < -3.43 or > 3.43, relative to the control mean], with the aim of obtaining personalised QSM profiles. RESULTS: Using two-pass QSM, we achieved susceptibility maps with a substantial increase in quality and reduction in artefacts irrespective of the presence of large focal lesions, compared to single-pass QSM. In addition, VBG minimised the loss of GM regions and exclusion of patients due to failures in the region delineation step. Our findings revealed deviations in magnetic susceptibility measures from the HC group that differed across individual TBI patients. These changes included both increases and decreases in magnetic susceptibility values in multiple GM regions across the brain. CONCLUSIONS: We illustrate how to obtain magnetic susceptibility values at the individual level and to build personalised QSM profiles in ms-TBI patients. Our approach opens the door for QSM investigations in more severely injured patients. Such profiles are also critical to overcome the inherent heterogeneity of clinical populations, such as ms-TBI, and to characterize the underlying mechanisms of neurodegeneration at the individual level more precisely. Moreover, this new personalised QSM profiling could in the future assist clinicians in assessing recovery and formulating a neuroscience-guided integrative rehabilitation program tailored to individual TBI patients.

Individualised profiling of white matter organisation in moderate-to-severe traumatic brain injury patients.

BACKGROUND AND PURPOSE: Approximately 65% of moderate-to-severe traumatic brain injury (m-sTBI) patients present with poor long-term behavioural outcomes, which can significantly impair activities of daily living. Numerous diffusion-weighted MRI studies have linked these poor outcomes to decreased white matter integrity of several commissural tracts, association fibres and projection fibres in the brain. However, most studies have focused on group-based analyses, which are unable to deal with the substantial between-patient heterogeneity in m-sTBI. As a result, there is increasing interest and need in conducting individualised neuroimaging analyses. MATERIALS AND METHODS: Here, we generated a detailed subject-specific characterisation of microstructural organisation of white matter tracts in 5 chronic patients with m-sTBI (29 - 49y, 2 females), presented as a proof-of-concept. We developed an imaging analysis framework using fixel-based analysis and TractLearn to determine whether the values of fibre density of white matter tracts at the individual patient level deviate from the healthy control group (n = 12, 8F, Mage = 35.7y, age range 25 - 64y). RESULTS: Our individualised analysis revealed unique white matter profiles, confirming the heterogenous nature of m-sTBI and the need of individualised profiles to properly characterise the extent of injury. Future studies incorporating clinical data, as well as utilising larger reference samples and examining the test-retest reliability of the fixel-wise metrics are warranted. CONCLUSIONS: Individualised profiles may assist clinicians in tracking recovery and planning personalised training programs for chronic m-sTBI patients, which is necessary to achieve optimal behavioural outcomes and improved quality of life.

Examination of Cerebellar Grey-Matter Volume in Children with Neurodevelopmental Disorders: a Coordinated Analysis Using the ACAPULCO Algorithm.

Alterations in cerebellar morphology relative to controls have been identified in children with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and developmental coordination disorder (DCD). However, it is not clear if common cerebellar regions are affected in each neurodevelopmental disorder and whether cerebellar morphological changes reflect a generic developmental vulnerability, or disorder-specific characteristic. The present study concatenated anatomical MRI scans from five existing cohorts, resulting in data from 252 children between the age of 7 and 12 years (ASD = 58, ADHD = 86, DCD = 22, Controls = 86). The ACAPULCO processing pipeline for cerebellar segmentation was conducted on T1-weighted images. A voxel-wise approach with general linear model was used to compare grey-matter volume of the 27 cerebellar lobules between each clinical group and controls. Our findings revealed that the ADHD group showed lower grey-matter volume in the left Crus I - part of the executive/non-motor portion of the cerebellum, relative to controls (p = 0.02). This no longer remained significant after controlling for medication status. There were no regions of significant differences in volume of the cerebellar lobules in ASD or DCD compared to controls. Future work will conduct harmonisation of behavioural data (cognitive and motor outcomes) across cohorts, enabling more advanced analyses to identify symptom cluster across neurodevelopmental disorders.

Individual differences in attentional lapses are associated with fiber-specific white matter microstructure in healthy adults.

Attentional lapses interfere with goal-directed behaviors, which may result in harmless (e.g., not hearing instructions) or severe (e.g., fatal car accident) consequences. Task-related functional MRI (fMRI) studies have shown a link between attentional lapses and activity in the frontoparietal network. Activity in this network is likely to be mediated by the organization of the white matter fiber pathways that connect the regions implicated in the network, such as the superior longitudinal fasciculus I (SLF-I). In the present study, we investigate the relationship between susceptibility to attentional lapses and relevant white matter pathways in 36 healthy adults (23 females, Mage  = 31.56 years). Participants underwent a diffusion MRI (dMRI) scan and completed the global-local task to measure attentional lapses, similar to previous fMRI studies. Applying the fixel-based analysis framework for fiber-specific analysis of dMRI data, we investigated the association between attentional lapses and variability in microstructural fiber density (FD) and macrostructural (morphological) fiber-bundle cross section (FC) in the SLF-I. Our results revealed a significant negative association between higher total number of attentional lapses and lower FD in the left SLF-I. This finding indicates that the variation in the microstructure of a key frontoparietal white matter tract is associated with attentional lapses and may provide a trait-like biomarker in the general population. However, SLF-I microstructure alone does not explain propensity for attentional lapses, as other factors such as sleep deprivation or underlying psychological conditions (e.g., sleep disorders) may also lead to higher susceptibility in both healthy people and those with neurological disorders.

Navigating the link between processing speed and network communication in the human brain.

Processing speed on cognitive tasks relies upon efficient communication between widespread regions of the brain. Recently, novel methods of quantifying network communication like 'navigation efficiency' have emerged, which aim to be more biologically plausible compared to traditional shortest path length-based measures. However, it is still unclear whether there is a direct link between these communication measures and processing speed. We tested this relationship in forty-five healthy adults (27 females), where processing speed was defined as decision-making time and measured using drift rate from the hierarchical drift diffusion model. Communication measures were calculated from a graph theoretical analysis of the whole-brain structural connectome and of a task-relevant fronto-parietal structural subnetwork, using the large-scale Desikan-Killiany atlas. We found that faster processing speed on trials that require greater cognitive control are correlated with higher navigation efficiency (of both the whole-brain and the task-relevant subnetwork). In contrast, faster processing speed on trials that require more automatic processing are correlated with shorter path length within the task-relevant subnetwork. Our findings reveal that differences in the way communication is modelled between shortest path length and navigation may be sensitive to processing of automatic and controlled responses, respectively. Further, our findings suggest that there is a relationship between the speed of cognitive processing and the structural constraints of the human brain network.

Contrasting predictions of low- and high-threshold models for the detection of changing visual features.

Change blindness is the failure of observers to notice otherwise obvious changes to a visual scene when those changes are masked in some way (eg by blotches or a blanking ofthe screen). Typically, change blindness is taken as evidence that our representation of the visual world is capacity limited. The locus of this capacity limit is thought to be visual short-term memory (vSTM). The capacity of vSTM is usually estimated with a high-threshold model which assumes that each element in the stimulus array is either fully encoded or not encoded at all, and, furthermore, that false alarms can arise only by guessing, not by noise. Low-threshold models, by contrast, suggest that false alarms can arise by noise at the level of detection/discrimination and/or decision. In this study, we use a well-controlled stimulus display in which a single element changes over a blanking of the screen and contrast predictions from a popular high-threshold model of vSTM with the predictions of a low-threshold model (specifically, the sample-size model) of visual search and vSTM. The data were better predicted by the low-threshold model.

Thresholds for the detection of changing visual features.

Change blindness refers to the difficulty observers have in detecting otherwise obvious changes to visual stimuli, when these changes are masked in some way. Typically, change blindness is studied by using complex visual scenes and complex changes to these scenes. In the current study, we used a more controlled visual environment, presenting observers with a series of oriented, sinusoidal patterns (Gabors), one of which underwent a change during a blanking of the screen. Changes were made to different features (size, colour, spatial frequency, and speed) with the target-distractor discriminability varying. The detectability of these changes was quantified by calculating psychometric functions and thresholds for each individual observer. Thresholds for the detection of changing features were higher than those for non-changing features, but thresholds for both tasks show consistency across observers. Psychometric-function slopes show consistency across observers and change type only for non-changing targets. For changing targets, psychometric-function slopes show no obvious pattern across observers or change types. We suggest this reflects vSTM treating different features as abstract, interchangeable tokens, as alternative explanations (such as additional noise in vSTM) can be ruled out.

Flexible resource allocation for the detection of changing visual features.

Failure to detect change under circumstances where visual input is interrupted or attention is distracted is indicative of the capacity limits of visual short-term memory. The current study attempts to probe the nature of these limits. In experiment 1, the appearance of single Gabor patches was altered across colour, size, or speed, and set size was manipulated by means of a visual cue. In experiment 2, performance for detecting single and multiple changes to Gabor patches was compared under the constraint that the inherent detectability of each individual change was the same. Experiment 1 yielded a particular set size (4) and a particular level of change magnitude at which performance was equivalent across change type. On the basis of these parameter values, experiment 2 revealed that the detectability of two features changing within one object was the same as the detectability of a single feature changing across two objects, and that this level of detectability could be predicted by a simple model of probability summation. Together, these results suggest that performance is determined by the magnitude of featural changes independently of the way they are distributed across objects. We suggest they are adequately explained by a flexible-resource-allocation model rather than a slot-allocation model.

Adaptation to combinations of form, colour, and movement.

Observers typically report illusory colour on achromatic gratings after being adapted to orthogonally oriented gratings presented in complementary colours, where the colour apparent on each grating is complementary to the one that had been presented with that grating during adaptation (McCollough, 1965 Science 149 1115-1116). We used this procedure, but presented homogenous fields at test instead of achromatic gratings. When adaptation stimuli moved in directions locally orthogonal to their orientation, we found that, for up to 7-8 min after adaptation, a flower-like illusory pattern was evident on both homogenous fields; after this time illusory radial lines and concentric circles were evident and were colour-contingent (eg for adaptation with green concentric circles and magenta radial lines, concentric circles were apparent on a magenta test field and radial lines were apparent on a green test field). When stimuli were stationary during induction, colour-contingent illusory forms were also apparent at test. The results demonstrate that an aftereffect, reciprocal to the McCollough effect, can be produced under appropriate induction conditions, and that this effect is not due to retinal afterimages.