Brain-behavior Relationships Research Articles

Test-retest reliability of resting-state EEG in young and older adults.

The quantification of resting-state electroencephalography (EEG) is associated with a variety of measures. These include power estimates at different frequencies, microstate analysis, and frequency-resolved source power and connectivity analyses. Resting-state EEG metrics have been widely used to delineate the manifestation of cognition and to identify psychophysiological indicators of age-related cognitive decline. The reliability of the utilized metrics is a prerequisite for establishing robust brain-behavior relationships and clinically relevant indicators of cognitive decline. To date, however, test-retest reliability examination of measures derived from resting human EEG, comparing different resting-state measures between young and older participants, within the same adequately powered dataset, is lacking. The present registered report examined test-retest reliability in a sample of 95 young (age range: 20-35 years) and 93 older (age range: 60-80 years) participants. A good-to-excellent test-retest reliability was confirmed in both age groups for power estimates on both scalp and source levels as well as for the individual alpha peak power and frequency. Partial confirmation was observed for hypotheses stating good-to-excellent reliability of microstates measures and connectivity. Equal levels of reliability between the age groups were confirmed for scalp-level power estimates and partially so for source-level power and connectivity. In total, five out of the nine postulated hypotheses were empirically supported and confirmed good-to-excellent reliability of the most commonly reported resting-state EEG metrics.

Neural correlates of gait adaptation in younger and older adults

Mobility decline is a major concern for older adults. A key component of maintaining mobility with advancing age is the ability to learn and adapt to the environment. The split-belt treadmill paradigm is an experimental protocol that tests the ability to adapt to a dynamic environment. Here we examined the magnetic resonance imaging (MRI) derived structural neural correlates of individual differences in adaptation to split-belt walking for younger and older adults. We have previously shown that younger adults adopt an asymmetric walking pattern during split-belt walking, particularly in the medial-lateral (ML) direction, but older adults do not. We collected T_1-weighted and diffusion-weighted MRI scans to quantify brain morphological characteristics (i.e. in the gray matter and white matter) on these same participants. We investigated two distinct questions: (1) Are there structural brain metrics that are associated with the ability to adopt asymmetry during split-belt walking; and (2) Are there different brain-behavior relationships for younger and older adults? Given the growing evidence that indicates the brain has a critical role in the maintenance of gait and balance, we hypothesized that brain areas commonly associated with locomotion (i.e. basal ganglia, sensorimotor cortex, cerebellum) would be associated with ML asymmetry and that older adults would show more associations between split-belt walking and prefrontal brain areas. We identified multiple brain-behavior associations. More gray matter volume in the superior frontal gyrus and cerebellar lobules VIIB and VIII, more sulcal depth in the insula, more gyrification in the pre/post central gyri, and more fractional anisotropy in the corticospinal tract and inferior longitudinal fasciculus corresponded to more gait asymmetry. These associations did not differ between younger and older adults. This work progresses our understanding of how brain structure is associated with balance during walking, particularly during adaptation.

Comparing the brain-behaviour relationship in acute and chronic stroke aphasia.

In stroke aphasia, lesion volume is typically associated with aphasia severity. Although this relationship is likely present throughout recovery, different factors may affect lesion volume and behaviour early into recovery (acute) and in the later stages of recovery (chronic). Therefore, studies typically separate patients into two groups (acute/chronic), and this is often accompanied with arguments for and against using data from acute stroke patients over chronic. However, no comprehensive studies have provided strong evidence of whether the lesion-behaviour relationship early in recovery is comparable to later in the recovery trajectory. To that end, we investigated two aims: (i) whether lesion data from acute and chronic patients yield similar results in region-based lesion-symptom mapping analyses and (ii) if models based on one timepoint accurately predict the other. Lesions and aphasia severity scores from acute (N = 63) and chronic (N = 109) stroke survivors with aphasia were entered into separate univariate region-based lesion-symptom mapping analyses. A support vector regression model was trained on lesion data from either the acute or chronic data set to give an estimate of aphasia severity. Four model-based analyses were conducted: trained on acute/chronic using leave-one-out, tested on left-out behaviour or trained on acute/chronic to predict the other timepoint. Region-based lesion-symptom mapping analyses identified similar but not identical regions in both timepoints. All four models revealed positive correlations between actual and predicted Western Aphasia Battery-Revised aphasia-quotient scores. Lesion-to-behaviour predictions were almost equivalent when comparing within versus across stroke stage, despite differing lesion size/locations and distributions of aphasia severity between stroke timepoints. This suggests that research investigating the brain-behaviour relationship including subsets of patients from only one timepoint may also be applicable at other timepoints, although it is important to note that these comparable findings may only be seen using broad measures such as aphasia severity, rather than those aimed at identifying more specific deficits. Subtle differences found between timepoints may also be useful in understanding the nature of lesion volume and aphasia severity over time. Stronger correlations found when predicting acute behaviour (e.g. predicting acute: r = 0.6888, P < 0.001, predicting chronic r = 0.5014, P < 0.001) suggest that the acute lesion/perfusion patterns more accurately capture the critical changes in underlying vascular territories. Differences in critical brain regions between timepoints may shed light on recovery patterns. Future studies could focus on a longitudinal design to compare acute and chronic patients in a more controlled manner.

Disentangling Some Conceptual Knots.

Disentangling Some Conceptual Knots.

Improving the study of brain-behavior relationships by revisiting basic assumptions.

Neuroimaging research has been at the forefront of concerns regarding the failure of experimental findings to replicate. In the study of brain-behavior relationships, past failures to find replicable and robust effects have been attributed to methodological shortcomings. Methodological rigor is important, but there are other overlooked possibilities: most published studies share three foundational assumptions, often implicitly, that may be faulty. In this paper, we consider the empirical evidence from human brain imaging and the study of non-human animals that calls each foundational assumption into question. We then consider the opportunities for a robust science of brain-behavior relationships that await if scientists ground their research efforts in revised assumptions supported by current empirical evidence.

Shared pattern of impaired social communication and cognitive ability in the youth brain across diagnostic boundaries

BackgroundAbnormalities in brain structure are shared across diagnostic categories. Given the high rate of comorbidity, the interplay of relevant behavioural factors may also cross these classic boundaries. MethodsWe aimed to detect brain-based dimensions of behavioural factors using canonical correlation and independent component analysis in a clinical youth sample (n = 1732, 64 % male, age: 5–21 years). ResultsWe identified two correlated patterns of brain structure and behavioural factors. The first mode reflected physical and cognitive maturation (r = 0.92, p = .005). The second mode reflected lower cognitive ability, poorer social skills, and psychological difficulties (r = 0.92, p = .006). Elevated scores on the second mode were a common feature across all diagnostic boundaries and linked to the number of comorbid diagnoses independently of age. Critically, this brain pattern predicted normative cognitive deviations in an independent population-based sample (n = 1253, 54 % female, age: 8–21 years), supporting the generalisability and external validity of the reported brain-behaviour relationships. ConclusionsThese results reveal dimensions of brain-behaviour associations across diagnostic boundaries, highlighting potent disorder-general patterns as the most prominent. In addition to providing biologically informed patterns of relevant behavioural factors for mental illness, this contributes to a growing body of evidence in favour of transdiagnostic approaches to prevention and intervention.

Functional maturation in visual pathways predicts attention to the eyes in infant rhesus macaques: Effects of social status

Differences in looking at the eyes of others are one of the earliest behavioral markers for social difficulties in neurodevelopmental disabilities, including autism. However, it is unknown how early visuo-social experiences relate to the maturation of infant brain networks that process visual social stimuli. We investigated functional connectivity (FC) within the ventral visual object pathway as a contributing neural system. Densely sampled, longitudinal eye-tracking and resting state fMRI (rs-fMRI) data were collected from infant rhesus macaques, an important model of human social development, from birth through 6 months of age. Mean trajectories were fit for both datasets and individual trajectories from subjects with both eye-tracking and rs-fMRI data were used to test for brain-behavior relationships. Exploratory findings showed infants with greater increases in FC between left V1 to V3 visual areas have an earlier increase in eye-looking before 2 months. This relationship was moderated by social status such that infants with low social status had a stronger association between left V1 to V3 connectivity and eye-looking than high status infants. Results indicated that maturation of the visual object pathway may provide an important neural substrate supporting adaptive transitions in social visual attention during infancy.

Contribution of the stereoscopic representation of motion-in-depth during visually guided feedback control.

Considerable studies have focused on the neural basis of visually guided tracking movement in the frontoparallel plane, whereas the neural process in real-world circumstances regarding the influence of binocular disparity and motion-in-depth (MID) perception is less understood. Although the role of stereoscopic versus monoscopic MID information has been extensively described for visual processing, its influence on top-down regulation for motor execution has not received much attention. Here, we orthogonally varied the visual representation (stereoscopic versus monoscopic) and motion direction (depth motion versus bias depth motion versus frontoparallel motion) during visually guided tracking movements, with simultaneous functional near-infrared spectroscopy recordings. Results show that the stereoscopic representation of MID could lead to more accurate movements, which was supported by specific neural activity pattern. More importantly, we extend prior evidence about the role of frontoparietal network in brain-behavior relationship, showing that occipital area, more specifically, visual area V2/V3 was also robustly involved in the association. Furthermore, by using the stereoscopic representation of MID, it is plausible to detect robust brain-behavior relationship even with small sample size at low executive task demand. Taken together, these findings highlight the importance of the stereoscopic representation of MID for investigating neural correlates of visually guided feedback control.

Revisiting the Psychobiological Inhibition Model: a conceptual framework for understanding and treating insomnia using cognitive and behavioural therapeutics (CBTx).

Sleep is a biological imperative, so one might wonder "what has psychology got to do with it?" A person's behaviours, thoughts, emotions and interactions with the environment inevitably serve for good, or for ill, as the "setting conditions" for the expression of sleep. Put simply, although sleep is not a psychological phenomenon, sleep has crucial behavioural dependencies. Consequently, the Psychobiological Inhibition Model can embrace numerous, potentially interacting, pathways to the persistence of this ubiquitous disorder, providing an overarching conceptual framework for why and how insomnia develops. The clinical guideline treatment for chronic insomnia is cognitive behavioural therapy. Although typically delivered as "talking therapy", cognitive behavioural therapy is not some form of "psychobabble". Rather, the Psychobiological Inhibition Model framework for insomnia articulates how specific techniques can correct the various ways in which the expression of normal sleep and circadian brain-behaviour relationships have become disrupted. Indeed, cognitive behavioural therapy is best conceived of as an approach to treatment rather than being one specific agent. A shift in emphasis towards a cognitive and behavioural therapeutics formulary would provide improved impetus to understanding of how insomnia develops, and of how it may best be treated in any given patient.

Formal Neuropsychological Testing: Test Batteries, Interpretation, and Added Value in Practice.

Neuropsychologists evaluate patients for cognitive decline and dementia, using validated psychometric tests, along with behavioral observation, record review, clinical interview, and information about psychological functioning, to evaluate brain-behavior relationships and aid in differential diagnosis and treatment planning. Also considered are premorbid functioning, education, sex, socioeconomic status, primary language, culture, and race-related health disparities when selecting tests, interpreting performance, and providing a diagnostic impression. Neuropsychologists provide diagnostic clarity, explain symptoms and likely disease course to patients and family members, and assist the family with future planning, behavioral management strategies, and ways to mitigate caregiver burden.

Deciphering the clinico-radiological heterogeneity of dysexecutive Alzheimer's disease.

Dysexecutive Alzheimer's disease (dAD) manifests as a progressive dysexecutive syndrome without prominent behavioral features, and previous studies suggest clinico-radiological heterogeneity within this syndrome. We uncovered this heterogeneity using unsupervised machine learning in 52 dAD patients with multimodal imaging and cognitive data. A spectral decomposition of covariance between FDG-PET images yielded six latent factors ("eigenbrains") accounting for 48% of variance in patterns of hypometabolism. These eigenbrains differentially related to age at onset, clinical severity, and cognitive performance. A hierarchical clustering on the eigenvalues of these eigenbrains yielded four dAD subtypes, i.e. "left-dominant," "right-dominant," "bi-parietal-dominant," and "heteromodal-diffuse." Patterns of FDG-PET hypometabolism overlapped with those of tau-PET distribution and MRI neurodegeneration for each subtype, whereas patterns of amyloid deposition were similar across subtypes. Subtypes differed in age at onset and clinical severity where the heteromodal-diffuse exhibited a worse clinical picture, and the bi-parietal had a milder clinical presentation. We propose a conceptual framework of executive components based on the clinico-radiological associations observed in dAD. We demonstrate that patients with dAD, despite sharing core clinical features, are diagnosed with variability in their clinical and neuroimaging profiles. Our findings support the use of data-driven approaches to delineate brain-behavior relationships relevant to clinical practice and disease physiology.

Neural Basis of Internal Attention in Adults with Pure and Comorbid ADHD

Objective: To examine whether putatively atypical neuronal activity during internal attention in ADHD yields insights into processes underlying emotion dysregulation. Methods: We used a word processing paradigm to assess neural activations in adults with ADHD (N = 46) compared to controls (N = 43). We measured effects of valence, applied partial-least squares correlation analysis to assess multivariate brainbehavior relationships and ran subgroup analyses to isolate results driven by pure ADHD (N = 18). Results: During internal attention, ADHD, compared to controls, have (1) increased activation in the right angular gyrus (rAG), which appears driven by pure, not comorbid, ADHD and (2) diminished activation in the insula and fronto-striatal circuitry. Diminished activations were driven by negatively-valenced internal attention and negatively correlated with increased affective lability within the ADHD group. Conclusion: Internal attention in ADHD is associated with increased rAG activation, possibly reflecting difficulty converging external and internal information, and diminished activation within emotion regulation circuitry.

From Classical Methods to Generative Models: Tackling the Unreliability of Neuroscientific Measures in Mental Health Research

Advances in computational statistics and corresponding shifts in funding initiatives over the past few decades have led to a proliferation of neuroscientific measures being developed in the context of mental health research. Although such measures have undoubtedly deepened our understanding of neural mechanisms underlying cognitive, affective, and behavioral processes associated with various mental health conditions, the clinical utility of such measures remains underwhelming. Recent commentaries point toward the poor reliability of neuroscientific measures to partially explain this lack of clinical translation. Here, we provide a concise theoretical overview of how unreliability impedes clinical translation of neuroscientific measures; discuss how various modeling principles, including those from hierarchical and structural equation modeling frameworks, can help to improve reliability; and demonstrate how to combine principles of hierarchical and structural modeling within the generative modeling framework to achieve more reliable, generalizable measures of brain-behavior relationships for use in mental health research.

Action viewing and language in adolescents with autism spectrum disorder.

The mirror neuron system consists of fronto-parietal regions and responds to both goal-directed action execution and observation. The broader action observation network is specifically involved in observation of actions and is thought to play a role in understanding the goals of the motor act, the intention of others, empathy, and language. Many, but not all, studies have found mirror neuron system or action observation network dysfunction in autism spectrum disorder. The objective of this study was to use observation of a goal-directed action fMRI paradigm to examine the action observation network in autism spectrum disorder and to determine whether fronto-parietal activation is associated with language ability. Adolescents with autism spectrum disorder (n = 23) were compared to typically developing adolescents (n = 20), 11-17years. Overall, there were no group differences in activation, however, the autism spectrum group with impaired expressive language (n = 13) had significantly reduced inferior frontal and inferior parietal activation during action viewing. In controls, right supramarginal gyrus activation was associated with higher expressive language; bilateral supramarginal and left pars opercularis activation was associated with better verbal-gesture integration. Results suggest that action-observation network dysfunction may characterize a subgroup of individuals with autism spectrum disorder with expressive language deficits. Therefore, interventions that target this dysfunctional network may improve expressive language in this autism spectrum subgroup. Future treatment studies should individualize therapeutic approaches based on brain-behavior relationships.

History and State of Neuropsychology in Japan: A Modest Proposal from a Clinical Psychological Perspective

Introduction: Neuropsychology is a branch of clinical psychology that specializes in brain-behavior relationships by assessing cognition, behavior, and emotion. Neuropsychology was initially developed in the United States and Europe, and their practices have shaped other countries’ practices such as Japan. However, neuropsychology in Japan also has its own unique history. Aims: The present paper aims to discuss the history, work environment and licensure, and prospects of Japanese neuropsychology by comparing them to those in the United States. Methods: Information on four topics, including 1) the history and development of neuropsychology and the license of a clinical neuropsychologist in the United States, 2) the history and current situation of neuropsychology in Japan, 3) the background and process of the licensure in clinical psychology and neuropsychology in Japan, and 4) future directions and recommendations, were gathered through literature searches, official organization websites, and personal communication with clinical psychologists and other professionals in Japan. Results: While clinical neuropsychologists in the United States have a background in clinical psychology, most of the people conducting neuropsychological assessments and research in Japan are physicians, occupational therapists, and speech-language-hearing therapists. This is believed to be due to differences in the system of health insurance, education and training, cultural factors shaping psychology practice in Japan, funding opportunities, and the research environment. Conclusion: The care of patients who have neurological injuries and illnesses is one of the most crucial tasks for clinical neuropsychologists. It is important for clinical neuropsychologists in Japan to improve their knowledge and skills in clinical psychology to match global standards.

A common low dimensional structure of cognitive impairment in stroke and brain tumors

IntroductionNeuropsychological studies infer brain-behavior relationships from focal lesions like stroke and tumors. However, these pathologies impair brain function through different mechanisms even when they occur at the same brain’s location. The aim of this study was to compare the profile of cognitive impairment in patients with brain tumors vs. stroke and examine the correlation with lesion location in each pathology. MethodsPatients with first time stroke (n = 77) or newly diagnosed brain tumors (n = 76) were assessed with a neuropsychological battery. Their lesions were mapped with MRI scans. Test scores were analyzed using principal component analysis (PCA) to measure their correlation, and logistic regression to examine differences between pathologies. Next, with ridge regression we examined whether lesion features (location, volume) were associated with behavioral performance. ResultsThe PCA showed a similar cognitive impairment profile in tumors and strokes with three principal components (PCs) accounting for about half of the individual variance. PC1 loaded on language, verbal memory, and executive/working memory; PC2 loaded on general performance, visuo-spatial attention and memory, and executive functions; and, PC3 loaded on calculation, reading and visuo-spatial attention. The average lesion distribution was different, and lesion location was correlated with cognitive deficits only in stroke. Logistic regression found language and calculation more affected in stroke, and verbal memory and verbal fluency more affected in tumors. ConclusionsA similar low dimensional set of behavioral impairments was found both in stroke and brain tumors, even though each pathology caused some specific deficits in different domains. The lesion distribution was different for stroke and tumors and correlated with behavioral impairment only in stroke.

Mapping spoken language and cognitive deficits in post-stroke aphasia

Aphasia is an acquired disorder caused by damage, most commonly due to stroke, to brain regions involved in speech and language. While language impairment is the defining symptom of aphasia, the co-occurrence of non-language cognitive deficits and their importance in predicting rehabilitation and recovery outcomes is well documented. However, people with aphasia (PWA) are rarely tested on higher-order cognitive functions, making it difficult for studies to associate these functions with a consistent lesion correlate. Broca’s area is a particular brain region of interest that has long been implicated in speech and language production. Contrary to classic models of speech and language, cumulative evidence shows that Broca’s area and surrounding regions in the left inferior frontal cortex (LIFC) are involved in, but not specific to, speech production. In this study we aimed to explore the brain-behaviour relationships between tests of cognitive skill and language abilities in thirty-six adults with long-term speech production deficits caused by post-stroke aphasia.Our findings suggest that non-linguistic cognitive functions, namely executive functions and verbal working memory, explain more of the behavioural variance in PWA than classical language models imply. Additionally, lesions to the LIFC, including Broca’s area, were associated with non-linguistic executive (dys)function, suggesting that lesions to this area are associated with non-language-specific higher-order cognitive deficits in aphasia. Whether executive (dys)function – and its neural correlate in Broca’s area – contributes directly to PWA’s language production deficits or simply co-occurs with it, adding to communication difficulties, remains unclear. These findings support contemporary models of speech production that place language processing within the context of domain-general perception, action and conceptual knowledge. An understanding of the covariance between language and non-language deficits and their underlying neural correlates will inform better targeted aphasia treatment and outcomes.

Gray matter microstructure differences in autistic males: A gray matter based spatial statistics study

BackgroundAutism spectrum disorder (ASD) is a complex neurodevelopmental condition. Understanding the brain’s microstructure and its relationship to clinical characteristics is important to advance our understanding of the neural supports underlying ASD. In the current work, we implemented Gray-Matter Based Spatial Statistics (GBSS) to examine and characterize cortical microstructure and assess differences between typically developing (TD) and autistic males. MethodsA multi-shell diffusion MRI (dMRI) protocol was acquired from 83 TD and 70 autistic males (5-to-21-years) and fit to the DTI and NODDI models. GBSS was performed for voxelwise analysis of cortical gray matter (GM). General linear models were used to investigate group differences, while age-by-group interactions assessed age-related differences between groups. Within the ASD group, relationships between cortical microstructure and measures of autistic symptoms were investigated. ResultsAll dMRI measures were significantly associated with age across the GM skeleton. Group differences and age-by-group interactions are reported. Group-wise increases in neurite density in autistic individuals were observed across frontal, temporal, and occipital regions of the right hemisphere. Significant age-by-group interactions of neurite density were observed within the middle frontal gyrus, precentral gyrus, and frontal pole. Negative relationships between neurite dispersion and the ADOS-2 Calibrated Severity Scores (CSS) were observed within the ASD group. DiscussionFindings demonstrate group and age-related differences between groups in neurite density in ASD across right-hemisphere brain regions supporting cognitive processes. Results provide evidence of altered neurodevelopmental processes affecting GM microstructure in autistic males with implications for the role of cortical microstructure in the level of autistic symptoms. ConclusionUsing dMRI and GBSS, our findings provide new insights into group and age-related differences of the GM microstructure in autistic males. Defining where and when these cortical GM differences arise will contribute to our understanding of brain-behavior relationships of ASD and may aid in the development and monitoring of targeted and individualized interventions.

Neurocognitive and mental health impact of adrenoleukodystrophy across the lifespan: Insights for the era of newborn screening.

X-linked adrenoleukodystrophy (ALD) is a rare inherited neurological disorder that poses considerable challenges for clinical management throughout the lifespan. Although males are generally more severely affected than females, the time course and presentation of clinical symptoms are otherwise difficult to predict. Opportunities to improve outcomes for individuals with ALD are rapidly expanding due to the introduction of newborn screening programs for this condition and an evolving treatment landscape. The aim of this comprehensive review is to synthesize current knowledge regarding the neurocognitive and mental health effects of ALD. This review provides investigators and clinicians with context to improve case conceptualization, inform prognostic counseling, and optimize neuropsychological and mental health care for patients and their families. Results highlight key predictive factors and brain-behavior relationships associated with the diverse manifestations of ALD. The review also discusses considerations for endpoints within clinical trials and identifies gaps to address in future research.

Interaction Between Memory Load and Experimental Design on Brain Connectivity and Network Topology.

The conventional approach to investigating functional connectivity in the block-designed study usually concatenates task blocks or employs residuals of task activation. While providing many insights into brain functions, the block design adds more manipulation in functional network analysis that may reduce the purity of the blood oxygenation level-dependent signal. Recent studies utilized one single long run for task trials of the same condition, the so-called continuous design, to investigate functional connectivity based on task functional magnetic resonance imaging. Continuous brain activities associated with the single-task condition can be directly utilized for task-related functional connectivity assessment, which has been examined for working memory, sensory, motor, and semantic task experiments in previous research. But it remains unclear how the block and continuous design influence the assessment of task-related functional connectivity networks. This study aimed to disentangle the separable effects of block/continuous design and working memory load on task-related functional connectivity networks, by using repeated-measures analysis of variance. Across 50 young healthy adults, behavioral results of accuracy and reaction time showed a significant main effect of design as well as interaction between design and load. Imaging results revealed that the cingulo-opercular, fronto-parietal, and default model networks were associated with not only task activation, but significant main effects of design and load as well as their interaction on intra- and inter-network functional connectivity and global network topology. Moreover, a significant behavior-brain association was identified for the continuous design. This work has extended the evidence that continuous design can be used to study task-related functional connectivity and subtle brain-behavioral relationships.