Reliability of single-subject neural activation patterns in speech production tasks

Traditional group fMRI (functional magnetic resonance imaging) analyses are not designed to detect individual differences that may be crucial to better understanding speech disorders. Single-subject research could therefore provide a richer characterization of the neural substrates of speech production in development and disease. Before this line of research can be tackled, however, it is necessary to evaluate whether healthy individuals exhibit reproducible brain activation across multiple sessions during speech production tasks. In the present study, we evaluated the reliability and discriminability of cortical functional magnetic resonance imaging data from twenty neurotypical subjects who participated in two experiments involving reading aloud mono- or bisyllabic speech stimuli. Using traditional methods like the Dice and intraclass correlation coefficients, we found that most individuals displayed moderate to high reliability, with exceptions likely due to increased head motion in the scanner. Further, this level of reliability for speech production was not directly correlated with reliable patterns in the underlying average blood oxygenation level dependent signal across the brain. Finally, we found that a novel machine-learning subject classifier could identify these individuals by their speech activation patterns with 97% accuracy from among a dataset of seventy-five subjects. These results suggest that single-subject speech research would yield valid results and that investigations into the reliability of speech activation in people with speech disorders are warranted.Accepted manuscrip

Fluctuations between high- and low-modularity topology in time-resolved functional connectivity

Modularity is an important topological attribute for functional brain networks. Recent studies have reported that modularity of functional networks varies not only across individuals being related to demographics and cognitive performance, but also within individuals co-occurring with fluctuations in network properties of functional connectivity, estimated over short time intervals. However, characteristics of these time-resolved functional networks during periods of high and low modularity have remained largely unexplored. In this study we investigate spatiotemporal properties of time-resolved networks in the high and low modularity periods during rest, with a particular focus on their spatial connectivity patterns, temporal homogeneity and test-retest reliability. We show that spatial connectivity patterns of time-resolved networks in the high and low modularity periods are represented by increased and decreased dissociation of the default mode network module from task-positive network modules, respectively. We also find that the instances of time-resolved functional connectivity sampled from within the high (low) modularity period are relatively homogeneous (heterogeneous) over time, indicating that during the low modularity period the default mode network interacts with other networks in a variable manner. We confirmed that the occurrence of the high and low modularity periods varies across individuals with moderate inter-session test-retest reliability and that it is correlated with previously-reported individual differences in the modularity of functional connectivity estimated over longer timescales. Our findings illustrate how time-resolved functional networks are spatiotemporally organized during periods of high and low modularity, allowing one to trace individual differences in long-timescale modularity to the variable occurrence of network configurations at shorter timescales.Comment: Reorganized the paper; to appear in NeuroImage; arXiv abstract shortened to fit within character limit

INCITE: A randomised trial comparing constraint induced movement therapy and bimanual training in children with congenital hemiplegia

Background: Congenital hemiplegia is the most common form of cerebral palsy (CP) accounting for 1 in 1300 live births. These children have limitations in capacity to use the impaired upper limb and bimanual coordination deficits which impact on daily activities and participation in home, school and community life. There are currently two diverse intensive therapy approaches. Traditional therapy has adopted a bimanual approach (BIM training) and recently, constraint induced movement therapy (CIMT) has emerged as a promising unimanual approach. Uncertainty remains about the efficacy of these interventions and characteristics of best responders. This study aims to compare the efficacy of CIMT to BIM training to improve outcomes across the ICF for school children with congenital hemiplegia

Subtypes of Memory Impairment in Patients with Temporal Lobe Epilepsy

Memory impairments are common in individuals with temporal lobe epilepsy (TLE). This is understandable given that temporal lobe brain structures involved in TLE play a central role in encoding memories. It is widely accepted that individuals whose seizure focus is in the left temporal lobe (LTLE) tend to have verbal memory impairments, whereas individuals whose seizure focus is in the right temporal lobe (RTLE) tend to have visuospatial memory impairments. However, evidence of functional subdivisions within the left and right temporal lobes in both the animal and human literature suggest that more specific subtypes of memory impairment may exist in TLE based on differences in seizure foci. The aim of this study was to identify more specific subtypes of memory-impairments in patients with intractable TLE using several measures of memory functioning and cluster analysis. Identification of more specific memory subtypes in TLE could have prognostic significance for patients and contribute to our knowledge about the organization of memory systems of the human brain. Four memory subtypes were identified in this sample: 1) patients with mild to moderate figural memory deficits; 2) patients with moderate to severe figural memory deficits, mild facial recognition deficits, and mild attention/concentration deficits; 3) patients with severe figural memory deficits and mild verbal episodic memory deficits; and 4) patients with no episodic or semantic memory deficits. Unexpectedly, the subtypes found did not exhibit the expected pattern of verbal memory impairments with left temporal lobe damage/dysfunction or visuospatial memory impairments with right temporal lobe damage/dysfunction. However, consistent with the literature, there was a trend towards some clusters with better verbal memory having higher left hippocampal volumes; and a trend towards one cluster with facial recognition deficits having lower anterior temporal lobe volumes. Small sample sizes in this study limited the ability to clearly validate many of the cluster differences, particularly differences in brain volumes. Nevertheless, the results of this study support the hypothesis that subtypes of memory impairment do exist in patients with TLE. With larger sample sizes, it is plausible that additional subtypes may be found, or the characteristics of the subtypes found may become clearer

Functional Imaging Connectome of the Human Brain and its Associations with Biological and Behavioral Characteristics

Functional connectome of the human brain explores the temporal associations of different brain regions. Functional connectivity (FC) measures derived from resting state functional magnetic resonance imaging (rfMRI) characterize the brain network at rest and studies have shown that rfMRI FC is closely related to individual subject\u27s biological and behavioral measures. In this thesis we investigate a large rfMRI dataset from the Human Connectome Project (HCP) and utilize statistical methods to facilitate the understanding of fundamental FC-behavior associations of the human brain. Our studies include reliability analysis of FC statistics, demonstration of FC spatial patterns, and predictive analysis of individual biological and behavioral measures using FC features. Covering both static and dynamic FC (sFC and dFC) characterizations, the baseline FC patterns in healthy young adults are illustrated. Predictive analyses demonstrate that individual biological and behavioral measures, such as gender, age, fluid intelligence and language scores, can be predicted using FC. While dFC by itself performs worse than sFC in prediction accuracy, if appropriate parameters and models are utilized, adding dFC features to sFC can significantly increase the predictive power. Results of this thesis contribute to the understanding of the neural underpinnings of individual biological and behavioral differences in the human brain

Neural correlates of cognitive intervention in persons at risk of developing Alzheimer's disease.

Cognitive training is an emergent approach that has begun to receive increased attention in recent years as a non-pharmacological, cost-effective intervention for Alzheimer's disease (AD). There has been increasing behavioral evidence regarding training-related improvement in cognitive performance in early stages of AD. Although these studies provide important insight about the efficacy of cognitive training, neuroimaging studies are crucial to pinpoint changes in brain structure and function associated with training and to examine their overlap with pathology in AD. In this study, we reviewed the existing neuroimaging studies on cognitive training in persons at risk of developing AD to provide an overview of the overlap between neural networks rehabilitated by the current training methods and those affected in AD. The data suggest a consistent training-related increase in brain activity in medial temporal, prefrontal, and posterior default mode networks, as well as increase in gray matter structure in frontoparietal and entorhinal regions. This pattern differs from the observed pattern in healthy older adults that shows a combination of increased and decreased activity in response to training. Detailed investigation of the data suggests that training in persons at risk of developing AD mainly improves compensatory mechanisms and partly restores the affected functions. While current neuroimaging studies are quite helpful in identifying the mechanisms underlying cognitive training, the data calls for future multi-modal neuroimaging studies with focus on multi-domain cognitive training, network level connectivity, and individual differences in response to training

A test-retest fMRI dataset for motor, language and spatial attention functions

Background Since its inception over twenty years ago, functional magnetic resonance imaging (fMRI) has been used in numerous studies probing neural underpinnings of human cognition. However, the between session variance of many tasks used in fMRI remains understudied. Such information is especially important in context of clinical applications. A test-retest dataset was acquired to validate fMRI tasks used in pre-surgical planning. In particular, five task-related fMRI time series (finger, foot and lip movement, overt verb generation, covert verb generation, overt word repetition, and landmark tasks) were used to investigate which protocols gave reliable single-subject results. Ten healthy participants in their fifties were scanned twice using an identical protocol 2–3 days apart. In addition to the fMRI sessions, high-angular resolution diffusion tensor MRI (DTI), and high-resolution 3D T1-weighted volume scans were acquired. Findings Reliability analyses of fMRI data showed that the motor and language tasks were reliable at the subject level while the landmark task was not, despite all paradigms showing expected activations at the group level. In addition, differences in reliability were found to be mostly related to the tasks themselves while task-by-motion interaction was the major confounding factor. Conclusions Together, this dataset provides a unique opportunity to investigate the reliability of different fMRI tasks, as well as methods and algorithms used to analyze, de-noise and combine fMRI, DTI and structural T1-weighted volume data

The Impact Of Transcatheter Aortic Valve Implantation (TAVI) On Cognition: Evaluating The Relationship Between Changes In Cognitive Function, Cerebral Injury, Physical Ability, And Mood

Aortic stenosis is a cardiovascular disease affecting 2 to 4% of U.S. adults over age 65 years old (Freeman & Otto, 2006). Aortic stenosis causes angina and syncope eventually leading to heart failure and death (Otto, 2006). Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement in patients with high surgical mortality risk (Kappetein, 2013). The TAVI is associated with increased cerebral injury, with silent ischemia reported in up to 90% of TAVI patients (Samim et al., 2015). The present study examines the relationship between cerebral injury, cognitive changes, and quality of life in TAVI patients. Participants (n = 40) completed a cognitive assessment one day before the TAVI and at one-month post-TAVI. The primary cognitive measure was the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Additional tests (letter fluency, Trail Making Test, Digit Span Backward and Stroop) were included as measures of executive function and working memory. Measures of functional ability (Physical Self-Maintenance Questionnaire, Functional Activities Questionnaire, Dementia Severity Rating Scale), mood (GDS), and quality of life (Kansas City Cardiomyopathy Questionnaire) were also included. Baseline and follow-up MRIs were completed for 22 participants. Baseline RBANS Total Index scores (M = 85.26, SD = 14.69) evidenced mild cognitive decline prior to the TAVI. At one month, there was significant improvement on RBANS Language Index (p = 0.014), RBANS Fluency (p = 0.023), RBANS Figure Recall (p = 0.027), GDS (p = 0.018), and KCCQ (p \u3c 0.001). There was a significant decline on RBANS List Recall (p = 0.001). Six participants (27%) obtained new cerebral lesions at one month. Participants with neuronal injury did not differ from those without at one month (RBANS Total Score, p = 0.45). TAVI is related to overall stable cognitive performance and improved quality of life. The relationship between cerebral ischemia following TAVI and negative cognitive consequences is not supported. Further research is required in the cognitive implications following TAVI