Pushing the Limits: Cognitive, Affective, and Neural Plasticity Revealed by an Intensive Multifaceted Intervention.

Scientific understanding of how much the adult brain can be shaped by experience requires examination of how multiple influences combine to elicit cognitive, affective, and neural plasticity. Using an intensive multifaceted intervention, we discovered that substantial and enduring improvements can occur in parallel across multiple cognitive and neuroimaging measures in healthy young adults. The intervention elicited substantial improvements in physical health, working memory, standardized test performance, mood, self-esteem, self-efficacy, mindfulness, and life satisfaction. Improvements in mindfulness were associated with increased degree centrality of the insula, greater functional connectivity between insula and somatosensory cortex, and reduced functional connectivity between posterior cingulate cortex (PCC) and somatosensory cortex. Improvements in working memory and reading comprehension were associated with increased degree centrality of a region within the middle temporal gyrus (MTG) that was extensively and predominately integrated with the executive control network. The scope and magnitude of the observed improvements represent the most extensive demonstration to date of the considerable human capacity for change. These findings point to higher limits for rapid and concurrent cognitive, affective, and neural plasticity than is widely assumed

Investigating White Matter Lesion Load, Intrinsic Functional Connectivity, and Cognitive Abilities in Older Adults

Changes to the while matter of the brain disrupt neural communication between spatially distributed brain regions and are associated with cognitive changes in later life. While approximately 95% of older adults experience these brain changes, not everyone who has significant white matter damage displays cognitive impairment. Few studies have investigated the association between white matter changes and cognition in the context of functional brain network integrity. This study used a data-driven, multivariate analytical model to investigate intrinsic functional connectivity patterns associated with individual variability in white matter lesion load as related to fluid and crystallized intelligence in a sample of healthy older adults (n = 84). Several primary findings were noted. First, a reliable pattern emerged associating whole-brain resting-state functional connectivity with individual variability in measures of white matter lesion load, as indexed by total white matter lesion volume and number of lesions. Secondly, white matter lesion load was associated with increased network disintegration and dedifferentiation. Specifically, lower white matter lesion load was associated with greater within- versus between-network connectivity. Higher white matter lesion load was associated with greater between-network connectivity compared to within. These associations between intrinsic functional connectivity and white matter lesion load were not reliably associated with crystallized and fluid intelligence performance. These results suggest that changes to the white matter of the brain in typically aging older adults are characterized by increased functional brain network dedifferentiation. The findings highlight the role of white matter lesion load in altering the functional network architecture of the brain

Social Cognitive and Affective Neural Substrates of Adolescent Transdiagnostic Symptoms

Indiana University-Purdue University Indianapolis (IUPUI)The social cognitive ability to identify another’s internal state and social affective ability to share another’s emotional experience, known as empathy, are integral to healthy social functioning. During tasks, neural systems active when adolescents empathize include cognitive (medial prefrontal cortex and posterior cingulate cortex with the dorsolateral prefrontal cortex) and affective (anterior insula and anterior cingulate cortex) regions that are consistent with the adult task-based literature implicating the default mode, salience, and frontoparietal networks. However, task-based studies are limited to examining neural regions probed by the task; thus, do not capture broader patterns of information processing associated with complex processes, such as empathy. Methods of functional connectivity capture broader patterns of information processing at the level of network connectivity. Although it has clear advantages in identifying neural vulnerabilities to disorder, functional connectivity has yet to be used in adolescent investigations of empathy. Via parent- and self-report, deficits in either cognitive or affective processes central to empathy associate with the most widely agreed on classifications of behavioral disorders in adolescents – transdiagnostic symptoms of internalizing and externalizing. However, this evidence relies exclusively on self-report measures and research has yet to examine the neural connectivity underlying transdiagnostic symptoms in relation to cognitive and affective empathy. What has yet to be known is (1) how the social cognitive and affective processes of empathy are functionally connected across a heterogeneous sample of adolescents and (2) the association of cognitive, affective, and imbalanced empathy with transdiagnostic symptoms. Addressing these gaps in knowledge is an important incremental step for specifying vulnerabilities not fully captured via subjective report alone. This information can be used to improve prevention and intervention strategies. The present study will examine the functional connectivity of neural networks underlying empathy in early to mid-adolescents and their association with transdiagnostic symptoms

Effective Connectivity of Functionally Anticorrelated Networks Under Lysergic Acid Diethylamide

Background: Classic psychedelic-induced ego dissolution involves a shift in the sense of self and a blurring of the boundary between the self and the world. A similar phenomenon is identified in psychopathology and is associated with the balance of anticorrelated activity between the default mode network, which directs attention inward, and the salience network, which recruits the dorsal attention network to direct attention outward. Methods: To test whether changes in anticorrelated networks underlie the peak effects of lysergic acid diethylamide (LSD), we applied dynamic causal modeling to infer effective connectivity of resting-state functional magnetic resonance imaging scans from a study of 25 healthy adults who were administered 100 μg of LSD or placebo. Results: We found that inhibitory effective connectivity from the salience network to the default mode network became excitatory, and inhibitory effective connectivity from the default mode network to the dorsal attention network decreased under the peak effect of LSD. Conclusions: The effective connectivity changes we identified may reflect diminution of the functional anticorrelation between resting-state networks that may be a key neural mechanism of LSD and underlie ego dissolution. Our findings suggest that changes to the sense of self and subject-object boundaries across different states of consciousness may depend upon the organized balance of effective connectivity of resting-state networks

Distinct patterns of thought mediate the link between brain functional connectomes and well-being

Ongoing thought patterns constitute important aspects of both healthy and abnormal human cognition. However, the neural mechanisms behind these daily experiences and their contribution to well-being remain a matter of debate. Here, using resting-state fMRI and retrospective thought sampling in a large neurotypical cohort (n = 211), we identified two distinct patterns of thought, broadly describing the participants’ current concerns and future plans, that significantly explained variability in the individual functional connectomes. Consistent with the view that ongoing thoughts are an emergent property of multiple neural systems, network-based analysis highlighted the central importance of both unimodal and transmodal cortices in the generation of these experiences. Importantly, while state-dependent current concerns predicted better psychological health, mediating the effect of functional connectomes, trait-level future plans were related to better social health, yet with no mediatory influence. Collectively, we show that ongoing thoughts can influence the link between brain physiology and well-being

Structural and Functional Imaging Correlates of Visual Hallucinations in Parkinson's Disease

PURPOSE OF REVIEW: To review recent structural and functional MRI studies of visual hallucinations in Parkinson's disease. RECENT FINDINGS: Previously, neuroimaging had shown inconsistent findings in patients with Parkinson's hallucinations, especially in studies examining grey matter volume. However, recent advances in structural and functional MRI techniques allow better estimates of structural connections, as well as the direction of connectivity in functional MRI. These provide more sensitive measures of changes in structural connectivity and allow models of the changes in directional functional connectivity to be tested. We identified 27 relevant studies and found that grey matter imaging continues to show heterogeneous findings in Parkinson's patients with visual hallucinations. Newer approaches in diffusion imaging and functional MRI are consistent with emerging models of Parkinson's hallucinations, suggesting shifts in attentional networks. In particular, reduced bottom-up, incoming sensory information, and over-weighting of top-down signals appear to be important drivers of visual hallucinations in Parkinson's disease

ADHD-200 Patient Characterization and Classification using Resting State Networks: A Dissertation

Attention Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric disorder of childhood that is characterized by symptoms of inattention, impulsivity/hyperactivity, or a combination of both. Intrinsic brain dysfunction in ADHD can be examined through various methods including resting state functional Magnetic Resonance Imaging (rs-fMRI), which investigates patients’ functional brain connections in the absence of an explicit task. To date, studies of group differences in resting brain connectivity between patients with ADHD and typically developing controls (TDCs) have revealed reduced connectivity within the Default Mode Network (DMN), a resting state network implicated in introspection, mind-wandering, and day-dreaming. However, few studies have addressed the use of resting state connectivity measures as a diagnostic aide for ADHD on the individual patient level. In the current work, we attempted first to characterize the differences in resting state networks, including the DMN and three attention networks (the salience network, the left executive network, and the right executive network), between a group of youth with ADHD and a group of TDCs matched for age, IQ, gender, and handedness. Significant over- and under-connections were found in the ADHD group in all of these networks compared with TDCs. We then attempted to use a support vector machine (SVM) based on the information extracted from resting state network connectivity to classify participants as “ADHD” or “TDC.” The IFGmiddle temporal network (66.8% accuracy), the parietal association network (86.6% specificity and 48.5% PPV), and a physiological noise component (sensitivity 39.7% and NPV 69.6%) performed the best classifications. Finally, we attempted to combine and utilize information from all the resting state networks that we identified to improve classification accuracy. Contrary to our hypothesis, classification accuracy decreased to 54-55% when this information was combined. Overall, the work presented here supports the theory that the ADHD brain is differently connected at rest than that of TDCs, and that this information may be useful for developing a diagnostic aid. However, because ADHD is such a heterogeneous disorder, each ADHD patient’s underlying brain deficits may be unique making it difficult to determine what connectivity information is diagnostically useful

Advances in functional neuroanatomy: a review of combined DTI and fMRI studies in healthy younger and older adults.

Structural connections between brain regions are thought to influence neural processing within those regions. It follows that alterations to the quality of structural connections should influence the magnitude of neural activity. The quality of structural connections may also be expected to differentially influence activity in directly versus indirectly connected brain regions. To test these predictions, we reviewed studies that combined diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) in younger and older adults. By surveying studies that examined relationships between DTI measures of white matter integrity and fMRI measures of neural activity, we identified variables that accounted for variability in these relationships. Results revealed that relationships between white matter integrity and neural activity varied with (1) aging (i.e., positive and negative DTI-fMRI relationships in younger and older adults, respectively) and (2) spatial proximity of the neural measures (i.e., positive and negative DTI-fMRI relationships when neural measures were extracted from adjacent and non-adjacent brain regions, respectively). Together, the studies reviewed here provided support for both of our predictions