Brain Connectivity changes after Stroke and Rehabilitation

Several cortical and subcortical areas of brain interact coherently during various tasks such as motor-imagery (MI) and motor-execution (ME) and even during resting-state (RS). How these interactions are affected following stroke and how the functional organization is regained from rehabilitative treatments as people begin to recover have not been systematically studied. Role of primary motor area during MI task and how this differs during ME task are still questions of interest. To answer such questions, we recorded functional magnetic resonance imaging (fMRI) signals from 30 participants: 17 young healthy controls and 13 aged stroke survivors following stroke and following rehabilitation - either mental practice (MP) or combined session of mental practice and physical therapy (MP + PT). All the participants performed RS task whereas stroke survivors performed MI and ME tasks as well. We investigated the activity of motor network consisting of the left primary motor area (LM1), the right primary motor area (RM1), the left pre-motor cortex (LPMC), the right pre-motor cortex (RPMC) and the midline supplementary motor area (SMA). In this dissertation, first, we report that during RS the causal information flow (i) between the regions was reduced significantly following stroke (ii) did not increase significantly after MP alone and (iii) among the regions after MP+PT increased significantly towards the causal flow values for young able-bodied people. Second, we found that there was suppressive influence of SMA on M1 during MI task where as the influence was unrestricted during ME task. We reported that following intervention the connection between PMC and M1 was stronger during MI task whereas along with connection from PMC to M1, SMA to M1 also dominated during ME task. Behavioral results showed significant improvement in sensation and motor scores and significant correlation between differences in Fugl-Meyer Assessment (FMA) scores and differences in causal flow values as well differences in endogenous connectivity measures before and after intervention. We conclude that the spectra of causal information flow can be used as a reliable biomarker for evaluating rehabilitation in stroke survivors. These studies deepen our understanding of motor network activity during the recovery of motor behaviors in stroke. Understanding the stroke specific effective connectivity may be clinically beneficial in identifying effective treatments to maximize functional recovery in stroke survivors

Higher Frequency Network Activity Flow Predicts Lower Frequency Node Activity in Intrinsic Low-Frequency BOLD Fluctuations

The brain remains electrically and metabolically active during resting conditions. The low-frequency oscillations (LFO) of the blood oxygen level-dependent (BOLD) signal of functional magnetic resonance imaging (fMRI) coherent across distributed brain regions are known to exhibit features of this activity. However, these intrinsic oscillations may undergo dynamic changes in time scales of seconds to minutes during resting conditions. Here, using wavelet-transform based timefrequency analysis techniques, we investigated the dynamic nature of default-mode networks from intrinsic BOLD signals recorded from participants maintaining visual fixation during resting conditions. We focused on the default-mode network consisting of the posterior cingulate cortex (PCC), the medial prefrontal cortex (mPFC), left middle temporal cortex (LMTC) and left angular gyrus (LAG). The analysis of the spectral power and causal flow patterns revealed that the intrinsic LFO undergo significant dynamic changes over time. Dividing the frequency interval 0 to 0.25 Hz of LFO into four intervals slow- 5 (0.01–0.027 Hz), slow-4 (0.027–0.073 Hz), slow-3 (0.073–0.198 Hz) and slow-2 (0.198–0.25 Hz), we further observed significant positive linear relationships of slow-4 in-out flow of network activity with slow-5 node activity, and slow-3 in-out flow of network activity with slow-4 node activity. The network activity associated with respiratory related frequency (slow- 2) was found to have no relationship with the node activity in any of the frequency intervals. We found that the net causal flow towards a node in slow-3 band was correlated with the number of fibers, obtained from diffusion tensor imaging (DTI) data, from the other nodes connecting to that node. These findings imply that so-called resting state is not ‘entirely’ at rest, the higher frequency network activity flow can predict the lower frequency node activity, and the network activity flow can reflect underlying structural connectivity

Oscillatory Motor Network Activity During Rest and Movement: An fNIRS Study

Coherent network oscillations (\u3c0.1 Hz) linking distributed brain regions are commonly observed in the brain during both rest and task conditions. What oscillatory network exists and how network oscillations change in connectivity strength, frequency and direction when going from rest to explicit task are topics of recent inquiry. Here, we study network oscillations within the sensorimotor regions of able-bodied individuals using hemodynamic activity as measured by functional near-infrared spectroscopy (fNIRS). Using spectral interdependency methods, we examined how the supplementary motor area (SMA), the left premotor cortex (LPMC) and the left primary motor cortex (LM1) are bound as a network during extended resting state (RS) and between-tasks resting state (btRS), and how the activity of the network changes as participants execute left, right, and bilateral hand (LH, RH, and BH) finger movements. We found: (i) power, coherence and Granger causality (GC) spectra had significant peaks within the frequency band (0.01–0.04 Hz) during RS whereas the peaks shifted to a bit higher frequency range (0.04–0.08 Hz) during btRS and finger movement tasks, (ii) there was significant bidirectional connectivity between all the nodes during RS and unidirectional connectivity from the LM1 to SMA and LM1 to LPMC during btRS, and (iii) the connections from SMA to LM1 and from LPMC to LM1 were significantly modulated in LH, RH, and BH finger movements relative to btRS. The unidirectional connectivity from SMA to LM1 just before the actual task changed to the bidirectional connectivity during LH and BH finger movement. The uni-directionality could be associated with movement suppression and the bi-directionality with preparation, sensorimotor update and controlled execution. These results underscore that fNIRS is an effective tool for monitoring spectral signatures of brain activity, which may serve as an important precursor before monitoring the recovery progress following brain injury

A randomized, double-blind, placebo-controlled trial of blue wavelength light exposure on sleep and recovery of brain structure, function, and cognition following mild traumatic brain injury.

Sleep and circadian rhythms are among the most powerful but least understood contributors to cognitive performance and brain health. Here we capitalize on the circadian resetting effect of blue-wavelength light to phase shift the sleep patterns of adult patients (aged 18-48 years) recovering from mild traumatic brain injury (mTBI), with the aim of facilitating recovery of brain structure, connectivity, and cognitive performance. During a randomized, double-blind, placebo-controlled trial of 32 adults with a recent mTBI, we compared 6-weeks of daily 30-min pulses of blue light (peak lambda = 469 nm) each morning versus amber placebo light (peak lambda= 578 nm) on neurocognitive and neuroimaging outcomes, including gray matter volume (GMV), resting-state functional connectivity, directed connectivity using Granger causality, and white matter integrity using diffusion tensor imaging (DTI). Relative to placebo, morning blue light led to phase-advanced sleep timing, reduced daytime sleepiness, and improved executive functioning, and was associated with increased volume of the posterior thalamus (i.e., pulvinar), greater thalamo-cortical functional connectivity, and increased axonal integrity of these pathways. These findings provide insight into the contributions of the circadian and sleep systems in brain repair and lay the groundwork for interventions targeting the retinohypothalamic system to facilitate injury recovery.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The Role of Prefrontal Cortical Surface Area and Volume in Preclinical Suicidal Ideation in a Non-Clinical Sample

Suicidal ideation (SUI) can occur in the absence of concomitant psychiatric diagnoses, and even normal levels can be problematic among individuals experiencing excess stress or lack of social support. The objective of this study was to investigate the neuroanatomical basis of SUI in non-clinical human populations who are within the normal limits of SUI, after accounting for elevated stress and perceived lack of social support. Neuroanatomical data were collected from 55 healthy individuals (mean age 30.9 +/- 8.1 years, 27 females) whose depression severity levels were below the Diagnostic and Statistical Manual of Mental Disorders criteria. Measures of SUI, aggression, stress, non-support, and treatment rejection were collected from the treatment-consideration scales (TCS) of the Personality Assessment Inventory (PAI). Correlations between standardized SUI scores and three brain morphometry measures, including vertex wise cortical thickness (CT), cortical surface area (CSA), and cortical volume (CV), were estimated for each participant, controlling for age, sex, intracranial volume, and the remaining TCS measures. We observed a significant negative association between scores on SUI and both CSA and CV (cluster-forming threshold of p < 0.005, clusterwise threshold of p < 0.05, FOR corrected for multiple comparisons) within the left rostral middle frontal gyrus. Our findings suggest that greater CSA and CV within the dorsolateral prefrontal cortex are associated with reduced SUI in a non-clinical population with mild levels of stress and perceived lack of social support. Because the dorsolateral prefrontal cortex has been broadly linked to cognitive reappraisal, self-critical thoughts, and emotional regulation, greater CSA and CV within these regions may lead to better mental health by protecting healthy individuals from engaging in SUI during periods of stress and perceived insufficient social support. As our data consisted of only healthy individuals with non-clinical levels of SUI, further investigation will be necessary to explore the neural basis of SUI in populations who may be at greater risk of future suicidal behavior.U.S. Army Medical Research and Materiel Command [W81XWH-09-1-0730]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Identification of structural brain alterations in adolescents with depressive symptomatology

Introduction: Depressive symptoms can emerge as early as childhood and may lead to adverse situations in adulthood. Studies have examined structural brain alternations in individuals with depressive symptoms, but findings remain inconclusive. Furthermore, previous studies have focused on adults or used a categorical approach to assess depression. The current study looks to identify grey matter volumes (GMV) that predict depressive symptomatology across a clinically concerning sample of adolescents. Methods: Structural MRI data were collected from 338 clinically concerning adolescents (mean age = 15.30 SD=2.07; mean IQ = 101.01 SD=12.43; 132 F). Depression symptoms were indexed via the Mood and Feelings Questionnaire (MFQ). Freesurfer was used to parcellate the brain into 68 cortical regions and 14 subcortical regions. GMV was extracted from all 82 brain areas. Multiple linear regression was used to look at the relationship between MFQ scores and region-specific GMV parameter. Follow up regressions were conducted to look at potential effects of psychiatric diagnoses and medication intake. Results: Our regression analysis produced a significant model (R2 = 0.446, F(86, 251) = 2.348, p \u3c 0.001). Specifically, there was a negative association between GMV of the left parahippocampal (B = -0.203, p = 0.005), right rostral anterior cingulate (B = -0.162, p = 0.049), and right frontal pole (B = -0.147, p = 0.039) and a positive association between GMV of the left bank of the superior temporal sulcus (B = 0.173, p = 0.029). Follow up analyses produced results proximal to the main analysis. Conclusions: Altered regional brain volumes may serve as biomarkers for the development of depressive symptoms during adolescence. These findings suggest a homogeneity of altered cortical structures in adolescents with depressive symptoms

Structural Atrophy of the Right Superior Frontal Gyrus in Adolescents With Severe Irritability

Severe irritability is common in youths with psychiatric disorders and results in significant dysfunction across domains (academic, social, and familial). Prior structural MRI studies in the pediatric population demonstrated that aberrations of cortical thickness (CT) and gray matter volume (GMV) in the fronto-striatal-temporal regions which have been associated with irritability. However, the directions of the correlations between structural alteration and irritability in the individual indices were not consistent. Thus, we aim to address this by implementing comprehensive assessments of CT, GMV, and local gyrification index (LGI) simultaneously in youths with severe levels of irritability by voxel-based morphometry and surface-based morphometry. One hundred and eight adolescents (46 youths with severe irritability and 62 healthy youths, average age = 14.08 years, standard deviation = 2.36) were scanned with a T1-weighted MRI sequence. The severity of irritability was measured using the affective reactivity index. In youths with severe irritability, there was decreased CT, GMV, and LGI in the right superior frontal gyrus (SFG) compared to healthy youths, and negative correlations between these indices of the SFG and irritability. Our findings suggest that structural deficits in the SFG, potentially related to its role in inhibitory control, may be critical for the neurobiology of irritability

Neuroimaging alterations of the suicidal brain and its relevance to practice: an updated review of MRI studies

Suicide is a leading cause of death in the United States. Historically, scientific inquiry has focused on psychological theory. However, more recent studies have started to shed light on complex biosignatures using MRI techniques, including task-based and resting-state functional MRI, brain morphometry, and diffusion tensor imaging. Here, we review recent research across these modalities, with a focus on participants with depression and Suicidal Thoughts and Behavior (STB). A PubMed search identified 149 articles specific to our population of study, and this was further refined to rule out more diffuse pathologies such as psychotic disorders and organic brain injury and illness. This left 69 articles which are reviewed in the current study. The collated articles reviewed point to a complex impairment showing atypical functional activation in areas associated with perception of reward, social/affective stimuli, top-down control, and reward-based learning. This is broadly supported by the atypical morphometric and diffusion-weighted alterations and, most significantly, in the network-based resting-state functional connectivity data that extrapolates network functions from well validated psychological paradigms using functional MRI analysis. We see an emerging picture of cognitive dysfunction evident in task-based and resting state fMRI and network neuroscience studies, likely preceded by structural changes best demonstrated in morphometric and diffusion-weighted studies. We propose a clinically-oriented chronology of the diathesis-stress model of suicide and link other areas of research that may be useful to the practicing clinician, while helping to advance the translational study of the neurobiology of suicide

Functional Organization and Restoration of the Brain Motor-Execution Network After Stroke and Rehabilitation

Multiple cortical areas of the human brain motor system interact coherently in the low frequency range (\u3c0.1 Hz), even in the absence of explicit tasks. Following stroke, cortical interactions are functionally disturbed. How these interactions are affected and how the functional organization is regained from rehabilitative treatments as people begin to recover motor behaviors has not been systematically studied. We recorded the intrinsic functional magnetic resonance imaging (fMRI) signals from 30 participants: 17 young healthy controls and 13 aged stroke survivors. Stroke participants underwent mental practice (MP) or both mental practice and physical therapy (MP+PT) within 14–51 days following stroke. We investigated the network activity of five core areas in the motor-execution network, consisting of the left primary motor area (LM1), the right primary motor area (RM1), the left pre-motor cortex (LPMC), the right pre-motor cortex (RPMC) and the supplementary motor area (SMA). We discovered that (i) the network activity dominated in the frequency range 0.06–0.08 Hz for all the regions, and for both able-bodied and stroke participants (ii) the causal information flow between the regions: LM1 and SMA, RPMC and SMA, RPMC and LM1, SMA and RM1, SMA and LPMC, was reduced significantly for stroke survivors (iii) the flow did not increase significantly after MP alone and (iv) the flow among the regions during MP+PT increased significantly. We also found that sensation and motor scores were significantly higher and correlated with directed functional connectivity measures when the stroke-survivors underwent MP+PT but not MP alone. The findings provide evidence that a combination of mental practice and physical therapy can be an effective means of treatment for stroke survivors to recover or regain the strength of motor behaviors, and that the spectra of causal information flow can be used as a reliable biomarker for evaluating rehabilitation in stroke survivors

Individual associations of adolescent alcohol use disorder versus cannabis use disorder symptoms in neural prediction error signaling and the response to novelty

Two of the most commonly used illegal substances by adolescents are alcohol and cannabis. Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with poorer decision-making in adolescents. In adolescents, level of AUD symptomatology has been negatively associated with striatal reward responsivity. However, little work has explored the relationship with striatal reward prediction error (RPE) representation and the extent to which any augmentation of RPE by novel stimuli is impacted. One-hundred fifty-one adolescents participated in the Novelty Task while undergoing functional magnetic resonance imaging (fMRI). In this task, participants learn to choose novel or non-novel stimuli to gain monetary reward. Level of AUD symptomatology was negatively associated with both optimal decision-making and BOLD response modulation by RPE within striatum and regions of prefrontal cortex. The neural alterations in RPE representation were particularly pronounced when participants were exploring novel stimuli. Level of CUD symptomatology moderated the relationship between novelty propensity and RPE representation within inferior parietal lobule and dorsomedial prefrontal cortex. These data expand on an emerging literature investigating individual associations of AUD symptomatology levels versus CUD symptomatology levels and RPE representation during reinforcement processing and provide insight on the role of neuro-computational processes underlying reinforcement learning/decision-making in adolescents