Establishing, versus Maintaining, Brain Function: A Neuro-computational Model of Cortical Reorganization after Injury to the Immature Brain

The effect of age at injury on outcome after acquired brain injury (ABI) has been the subject of much debate. Many argue that young brains are relatively tolerant of injury. A contrasting viewpoint due to Hebb argues that greater system integrity may be required for the initial establishment of a function than for preservation of an already-established function. A neuro-computational model of cortical map formation was adapted to examine effects of focal and distributed injury at various stages of development. This neural network model requires a period of training during which it self-organizes to establish cortical maps. Injuries were simulated by lesioning the model at various stages of this process and network function was monitored as "development" progressed to completion. Lesion effects are greater for larger, earlier, and distributed (multifocal) lesions. The mature system is relatively robust, particularly to focal injury. Activities in recovering systems injured at an early stage show changes that emerge after an asymptomatic interval. Early injuries cause qualitative changes in system behavior that emerge after a delay during which the effects of the injury are latent. Functions that are incompletely established at the time of injury may be vulnerable particularly to multifocal injury

Neurosystems: brain rhythms and cognitive processing

Neuronal rhythms are ubiquitous features of brain dynamics, and are highly correlated with cognitive processing. However, the relationship between the physiological mechanisms producing these rhythms and the functions associated with the rhythms remains mysterious. This article investigates the contributions of rhythms to basic cognitive computations (such as filtering signals by coherence and/or frequency) and to major cognitive functions (such as attention and multi-modal coordination). We offer support to the premise that the physiology underlying brain rhythms plays an essential role in how these rhythms facilitate some cognitive operations.098352 - Wellcome Trust; 5R01NS067199 - NINDS NIH HH

Altered Cortico-Cortical Brain Connectivity During Muscle Fatigue

Traditional brain activation studies using neuroimaging such as functional magnetic imaging (fMRI) have shown that muscle fatigue at submaximal intensity level is associated with increased brain activity in various cortical regions from low- to high-order motor centers. However, how these areas might interact remain unclear since previous activation studies related to motor control could not reveal information of between-area interaction. This issue can be addressed by evaluating brain activation data using the framework of connectivity analysis. Three types of brain connectivity, functional connectivity (FC), effective connectivity (EC) and structural connectivity (SC) have been examined to investigate the effect of voluntary muscle fatigue on the interaction within the cortical motor network. The aim of the study was to propose a new framework to reveal adaptive interactions among motor regions during progressive muscle fatigue. We hypothesized that the brain would exhibit fatigue-related alterations in the FC and EC. Ten healthy subjects performed repetitive handgrip contractions (3.5s ON/6.5s OFF) for 20 minutes at 50 maximal voluntary force (MVC) level using the right hand (fatigue task). Significant MVC reduction occurred at the end of the fatigue task, indicating muscle fatigue. Histogram and quantile analysis confirmed that FC of the brain increased in the severe fatigue stage (the last 100s of the fatigue task) compared with the minimal fatigue stage (the first 100s of the fatigue task). Structural equation modeling (SEM) was used to evaluate the EC of the brain during fatigue. We found the path from the prefrontal cortex (PFC) to the supplementary motor area (SMA) decreased during fatigue while the path from the premotor area (PMA) to the primary motor cortex (M1) increased. We also found supporting evidence from SC analysis using diffusion tensor image (DTI). The new framework of connectivity analysis, combining the work of SC, FC and EC, provides greater insights into the dynamic adaptations of int

Altered Cortico-Cortical Brain Connectivity During Muscle Fatigue

Traditional brain activation studies using neuroimaging such as functional magnetic imaging (fMRI) have shown that muscle fatigue at submaximal intensity level is associated with increased brain activity in various cortical regions from low- to high-order motor centers. However, how these areas might interact remain unclear since previous activation studies related to motor control could not reveal information of between-area interaction. This issue can be addressed by evaluating brain activation data using the framework of connectivity analysis. Three types of brain connectivity, functional connectivity (FC), effective connectivity (EC) and structural connectivity (SC) have been examined to investigate the effect of voluntary muscle fatigue on the interaction within the cortical motor network. The aim of the study was to propose a new framework to reveal adaptive interactions among motor regions during progressive muscle fatigue. We hypothesized that the brain would exhibit fatigue-related alterations in the FC and EC. Ten healthy subjects performed repetitive handgrip contractions (3.5s ON/6.5s OFF) for 20 minutes at 50 maximal voluntary force (MVC) level using the right hand (fatigue task). Significant MVC reduction occurred at the end of the fatigue task, indicating muscle fatigue. Histogram and quantile analysis confirmed that FC of the brain increased in the severe fatigue stage (the last 100s of the fatigue task) compared with the minimal fatigue stage (the first 100s of the fatigue task). Structural equation modeling (SEM) was used to evaluate the EC of the brain during fatigue. We found the path from the prefrontal cortex (PFC) to the supplementary motor area (SMA) decreased during fatigue while the path from the premotor area (PMA) to the primary motor cortex (M1) increased. We also found supporting evidence from SC analysis using diffusion tensor image (DTI). The new framework of connectivity analysis, combining the work of SC, FC and EC, provides greater insights into the dynamic adaptations of int

Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction.

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome

Theory of active self-organization of dense nematic structures in actin gels

The actin cytoskeleton is remarkably adaptable and multifunctional. It often organizes into nematic bundles such as contractile rings or stress fibers. However, how a uniform and isotropic actin gel self-organizes into dense nematic bundles is not understood. Here, using an active gel model accounting for nematic order and density variations, we identify a novel active patterning mechanism leading to dense nematic structures. Linear stability analysis and nonlinear finite element simulations establish the conditions for nematic bundle self-assembly and how active gel parameters control the architecture, orientation, connectivity and dynamics of self-organized patterns. Finally, we substantiate with discrete network simulations the main requirements for nematic bundle formation according to our theory, namely increased active tension perpendicular to the nematic direction and generalized active forces conjugate to nematic order. Our work portrays actin gels a reconfigurable active materials with a spontaneous tendency to develop patterns of dense nematic bundles.Comment: 11 pages, 4 figures, 1 supplementary PDF, 8 supplementary video

Getting to Know You: Key Clinical Concepts in Relationship-Based Interventions and Neurobehavioral Observations with Young Infants

The newborn infant is a social organism, pre-disposed to interact with his caregiver and able to elicit the kind of caregiving necessary for successful adaptation. The earliest developmental task of the newborn is to organize behavior to be able to play an active role in influencing the caregiving environment and eliciting the kind of support needed for development. This task is accomplished through the attainment of self-regulation or balanced neurobehavioral functioning of the infant\u27s autonomic, motor, state, and responsivity behavioral dimensions as described by Als

From holism to compositionality: memes and the evolution of segmentation, syntax, and signification in music and language

Steven Mithen argues that language evolved from an antecedent he terms “Hmmmmm, [meaning it was] Holistic, manipulative, multi-modal, musical and mimetic”. Owing to certain innate and learned factors, a capacity for segmentation and cross-stream mapping in early Homo sapiens broke the continuous line of Hmmmmm, creating discrete replicated units which, with the initial support of Hmmmmm, eventually became the semantically freighted words of modern language. That which remained after what was a bifurcation of Hmmmmm arguably survived as music, existing as a sound stream segmented into discrete units, although one without the explicit and relatively fixed semantic content of language. All three types of utterance – the parent Hmmmmm, language, and music – are amenable to a memetic interpretation which applies Universal Darwinism to what are understood as language and musical memes. On the basis of Peter Carruthers’ distinction between ‘cognitivism’ and ‘communicativism’ in language, and William Calvin’s theories of cortical information encoding, a framework is hypothesized for the semantic and syntactic associations between, on the one hand, the sonic patterns of language memes (‘lexemes’) and of musical memes (‘musemes’) and, on the other hand, ‘mentalese’ conceptual structures, in Chomsky’s ‘Logical Form’ (LF)

Role of Cerebrovascular Abnormality in Neurodegenerative Disease and Subcortical Ischemic Disease: CT Perfusion and PET Imaging

Clinical studies indicate that about 30% ~ 50% of patients have cognitive impairment after the first or recurrent stroke. Ischemic injury, particularly subcortical lesions, caused by stroke has been demonstrated to further exacerbate cognitive impairment of Alzheimer’s disease (AD) and vascular dementia. However, the mechanisms whereby cerebrovascular abnormalities contribute to neurodegeneration at early stage of disease and eventually to cognitive decline remain unclear. CT perfusion and positron emission tomography (PET) were used to investigate early mechanisms in a rat comorbid model of cerebral ischemia (CI) and β-amyloid (Aβ, a pathological hallmark of AD) toxicity, and in patients with small subcortical ischemic lesions. Chapter 2 investigates the early hemodynamic disturbances within the first month after transient CI insult in the presence of Aβ toxicity in the comorbid rat model. CT perfusion revealed significantly lower cerebral blood flow (CBF) and blood volume (CBV) at acute phase due to the transient ischemia, and increased CBF and CBV in the ipsilateral striatum of CI+Aβ and CI groups at the first week post ischemia. These results suggest that CI is the primary driving factor of cerebrovascular abnormalities at early stage, and prolonged hyperperfusion and hypervolemia may imply reperfusion-related injury and downstream inflammation. Chapter 3 further addresses these questions with CT Perfusion-PET imaging. Chapter 3 describes the temporal profiles of blood-brain barrier (BBB) disruption and neuroinflammation over 3 months after CI with and without concurrent Aβ toxicity in the comorbid rat model. CT perfusion showed significantly higher BBB permeability surface product (BBB-PS) in the ipsilateral striatum of CI+Aβ group at day 7, month 2 and 3, as compared to CI and sham group. PET imaging revealed the highest level of neuroinflammation as reflected by the significantly increased 18F-FEPPA uptake due to microglial activation in the striatal lesion of CI+Aβ group at day 7 and 14. The temporal features of these cererbrovascular and cellular changes may serve as early imaging biomarkers for development of cognitive impairment in high-risk patients post ischemic insult. Chapter 4 investigates the temporal changes in BBB-PS and cerebral perfusion using CT perfusion over the first 3 months after small lacunar/subcortical stroke in patients. This longitudinal investigation suggests the chronic BBB leakage detected by CT perfusion may contribute to cognitive impairment and associated pathology in lacunar/subcortical stroke. Overall, the imaging results presented in this thesis have demonstrated that BBB-PS, CBF, CBV and activated microglia can be used as imaging biomarkers for delineating the early pathogenic pattern and underlying contribution of cerebral ischemia to the disease development in the animal comorbid model and subcortical stroke patients