Effect of HAART on Brain Organization and Function in HIV-Negative Subjects

A core question in systems and computational neuroscience is how the brain represents information. Identifying principles of information coding in neural circuits is critical to understanding brain organization and function in sensory, motor, and cognitive neuroscience. This provides a conceptual bridge between the underlying biophysical mechanisms and the ultimate behavioral goals of the organism. Central to this framework is the question of computation: what are the relevant representations of input and output, and what algorithms govern the input-output transformation? Remarkably, evidence suggests that certain canonical computations exist across different circuits, brain regions, and species. Such computations are implemented by different biophysical and network mechanisms, indicating that the unifying target of conservation is the algorithmic form of information processing rather than the specific biological implementation. A prime candidate to serve as a canonical computation is divisive normalization, which scales the activity of a given neuron by the activity of a larger neuronal pool. This nonlinear transformation introduces an intrinsic contextual modulation into information coding, such that the selective response of a neuron to features of the input is scaled by other input characteristics. This contextual modulation allows the normalization model to capture a wide array of neural and behavioral phenomena not captured by simpler linear models of information processing. The generality and flexibility of the normalization model arises from the normalization pool, which allows different inputs to directly drive and suppress a given neuron, effectively separating information that drives excitation and contextual modulation. Originally proposed to describe responses in early visual cortex, normalization has been widely documented in different brain regions, hierarchical levels, and modalities of sensory processing; furthermore, recent work shows that the normalization extends to cognitive processes such as attention, multisensory integration, and decision making. This ubiquity reinforces the canonical nature of the normalization computation and highlights the importance of an algorithmic framework in linking biological mechanism and behavior.

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Monocyte Dysfunction, Activation, and Inflammation After Long-Term Antiretroviral Therapy in an African Cohort

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz320 ◽

2019 ◽

Vol 220 (9) ◽

pp. 1414-1419 ◽

Cited By ~ 7

Author(s):

Rose Nabatanzi ◽

Lois Bayigga ◽

Stephen Cose ◽

Sarah Rowland Jones ◽

Moses Joloba ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Viral Suppression ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Fatty Acid Binding ◽

Sustained Viral Suppression ◽

Immunodeficiency Virus ◽

And Function ◽

Hiv Negative

Abstract Background Monocyte dysfunction may persist during antiretroviral therapy (ART). Methods Frozen peripheral blood mononuclear cells of 30 human immunodeficiency virus (HIV)-infected ART-treated adults with sustained viral suppression and CD4 counts ≥500 cells/µL were consecutively analyzed for monocyte phenotypes and function. Results Nonclassical monocytes (CD14+, CD16++), interleukin (IL)-1β production, and expression of CD40 and CD86 were lower among ART-treated HIV-infected adults relative to age-matched HIV-negative adults (P = .01, P = .01, and P = .02, respectively). Intestinal fatty acid-binding protein, IL6, and soluble CD14 were higher among HIV-infected adults relative to HIV-negative adults (P = .0002, P = .04, and P = .0017, respectively). Conclusions Further investigation is required to understand drivers of persistent monocyte activation and dysfunction.

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Brain structure of perinatally HIV-infected patients on long-term treatment

Neurology Clinical Practice ◽

10.1212/cpj.0000000000000637 ◽

2019 ◽

Vol 9 (5) ◽

pp. 433-442 ◽

Cited By ~ 2

Author(s):

Malon Van den Hof ◽

Anne Marleen ter Haar ◽

Matthan W.A. Caan ◽

Rene Spijker ◽

Johanna H. van der Lee ◽

...

Keyword(s):

Brain Structure ◽

Diffusion Tensor ◽

Structure And Function ◽

Resonance Spectroscopy ◽

Cross Sectional ◽

Long Term Treatment ◽

Brain Structure And Function ◽

And Function ◽

Hiv Negative

ObjectiveWe aim to give an overview of the available evidence on brain structure and function in PHIV-infected patients (PHIV+) using long-term combination antiretroviral therapy (cART) and how differences change over time.MethodsWe conducted an electronic search using MEDLINE, Embase, and PsycINFO. We used the following selection criteria: cohort and cross-sectional studies that reported on brain imaging differences between PHIV+ of all ages who used cART for at least six months before neuroimaging and HIV-negative controls. Two reviewers independently selected studies, performed data extraction, and assessed quality of studies.ResultsAfter screening 1500 abstracts and 343 full-text articles, we identified 19 eligible articles. All included studies had a cross-sectional design and used MRI with different modalities: structural MRI (n = 7), diffusion tensor imaging (DTI) (n = 6), magnetic resonance spectroscopy (n = 5), arterial spin labeling (n = 1), and resting-state functional neuroimaging (n = 1). Studies showed considerable methodological limitations and heterogeneity, preventing us to perform meta-analyses. DTI data on white matter microstructure suggested poorer directional diffusion in cART-treated PHIV+ compared with controls. Other modalities were inconclusive.ConclusionEvidence may suggest brain structure and function differences in the population of PHIV+ on long-term cART compared with the HIV-negative population. Because of a small study population, and considerable heterogeneity and methodological limitations, the extent of brain structure and function differences on neuroimaging between groups remains unknown.

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Brain Plasticity and Behavior

Current Directions in Psychological Science ◽

10.1111/1467-8721.01210 ◽

2003 ◽

Vol 12 (1) ◽

pp. 1-5 ◽

Cited By ~ 74

Author(s):

Bryan Kolb ◽

Robbin Gibb ◽

Terry E. Robinson

Keyword(s):

Brain Plasticity ◽

Recovery Of Function ◽

Psychological Disorders ◽

Abnormal Behavior ◽

Brain Organization ◽

Functional Changes ◽

Brain Circuitry ◽

And Function ◽

And Behavior ◽

The Brain

Although the brain was once seen as a rather static organ, it is now clear that the organization of brain circuitry is constantly changing as a function of experience. These changes are referred to as brain plasticity, and they are associated with functional changes that include phenomena such as memory, addiction, and recovery of function. Recent research has shown that brain plasticity and behavior can be influenced by a myriad of factors, including both pre- and postnatal experience, drugs, hormones, maturation, aging, diet, disease, and stress. Understanding how these factors influence brain organization and function is important not only for understanding both normal and abnormal behavior, but also for designing treatments for behavioral and psychological disorders ranging from addiction to stroke.

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Regions and Connections: Complementary Approaches to Characterize Brain Organization and Function

The Neuroscientist ◽

10.1177/1073858419860115 ◽

2019 ◽

Vol 26 (2) ◽

pp. 117-133 ◽

Cited By ~ 4

Author(s):

Corey Horien ◽

Abigail S. Greene ◽

R. Todd Constable ◽

Dustin Scheinost

Keyword(s):

Functional Organization ◽

Brain Activity ◽

Functional Magnetic Resonance ◽

Resonance Imaging ◽

Brain Organization ◽

Neural Processes ◽

Relative Utility ◽

And Function ◽

Brain Behavior ◽

The Brain

Functional magnetic resonance imaging has proved to be a powerful tool to characterize spatiotemporal patterns of human brain activity. Analysis methods broadly fall into two camps: those summarizing properties of a region and those measuring interactions among regions. Here we pose an unappreciated question in the field: What are the strengths and limitations of each approach to study fundamental neural processes? We explore the relative utility of region- and connection-based measures in the context of three topics of interest: neurobiological relevance, brain-behavior relationships, and individual differences in brain organization. In each section, we offer illustrative examples. We hope that this discussion offers a novel and useful framework to support efforts to better understand the macroscale functional organization of the brain and how it relates to behavior.

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A little history goes a long way toward understanding why we study consciousness the way we do today

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1921623117 ◽

2020 ◽

Vol 117 (13) ◽

pp. 6976-6984 ◽

Cited By ~ 2

Author(s):

Joseph E. LeDoux ◽

Matthias Michel ◽

Hakwan Lau

Keyword(s):

Visual Stimulus ◽

Late 19Th Century ◽

Brain Organization ◽

Basic Principles ◽

Is Research ◽

Consciousness Studies ◽

1960S And 1970S ◽

And Function ◽

The Brain ◽

The Way

Consciousness is currently a thriving area of research in psychology and neuroscience. While this is often attributed to events that took place in the early 1990s, consciousness studies today are a continuation of research that started in the late 19th century and that continued throughout the 20th century. From the beginning, the effort built on studies of animals to reveal basic principles of brain organization and function, and of human patients to gain clues about consciousness itself. Particularly important and our focus here is research in the 1950s, 1960s, and 1970s involving three groups of patients—amnesia, split brain, and blindsight. Across all three groups, a similar pattern of results was found—the patients could respond appropriately to stimuli that they denied seeing (or in the case of amnesiacs, having seen before). These studies paved the way for the current wave of research on consciousness. The field is, in fact, still grappling with the implications of the findings showing that the ability to consciously know and report the identity of a visual stimulus can be dissociated in the brain from the mechanisms that underlie the ability to behave in a meaningful way to the same stimulus.

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Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

10.1101/2021.10.28.466336 ◽

2021 ◽

Author(s):

Justine Y Hansen ◽

Golia Shafiei ◽

Ross D Markello ◽

Kelly Smart ◽

Sylvia ML Cox ◽

...

Keyword(s):

Functional Organization ◽

Structural Connectivity ◽

Brain Organization ◽

Neurotransmitter Systems ◽

Oscillatory Dynamics ◽

Multi Scale ◽

Positron Emission ◽

Brain Structure And Function ◽

And Function ◽

Novel Associations

Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macroscale neuroanatomy and how they shape emergent function remains poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography scans in >1,200 healthy individuals to construct a whole-brain 3-D normative atlas of 18 receptors and transporters across 9 different neurotransmitter systems. We find that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncover a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we find both expected and novel associations between receptor distributions and cortical thinning patterns across 13 disorders. We replicate all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization.

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Innate lymphoid cell dysfunction during long-term suppressive antiretroviral therapy in an African cohort

BMC Immunology ◽

10.1186/s12865-021-00450-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Rose Nabatanzi ◽

Lois Bayigga ◽

Stephen Cose ◽

Glenda Canderan ◽

Sarah Rowland Jones ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Mononuclear Cells ◽

Lymphoid Cells ◽

Sub Saharan Africa ◽

Peripheral Blood Mononuclear ◽

Mucosal Surfaces ◽

Sub Saharan ◽

And Function ◽

Hiv Negative

Abstract Background Innate lymphoid cells (ILC) are lymphoid lineage innate immune cells that do not mount antigen-specific responses due to their lack of B and T-cell receptors. ILCs are predominantly found at mucosal surfaces, as gatekeepers against invading infectious agents through rapid secretion of immune regulatory cytokines. HIV associated destruction of mucosal lymphoid tissue depletes ILCs, among other immune dysfunctions. Studies have described limited restoration of ILCs during the first three years of combined antiretroviral therapy (cART). Little is known about restoration of ILCs during long-term cART, particularly in sub-Saharan Africa which hosts increasing numbers of adults with at least a decade of cART. Results We examined phenotypes and function of ILCs from peripheral blood mononuclear cells after 12 years of suppressive cART. We report that ILC1 frequencies (T-BET + CD127 + and CD161 +) were higher in cART-treated HIV-infected relative to age-matched health HIV-negative adults; P = 0.04 whereas ILC precursors (ILCP) were comparable in the two groups (P = 0.56). Interferon gamma (IFN-γ) secretion by ILC1 was higher among cART-treated HIV-infected relative to HIV-negative adults (P = 0.03). Conclusion HIV associated alteration of ILC persisted during cART and may likely affect the quality of host innate and adaptive immune responses during long-term cART.

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Edges in brain networks: contributions to models of structure and function

Network Neuroscience ◽

10.1162/netn_a_00204 ◽

2021 ◽

pp. 1-63

Author(s):

Joshua Faskowitz ◽

Richard F Betzel ◽

Olaf Sporns

Keyword(s):

Network Models ◽

Brain Network ◽

Higher Order ◽

Dynamic Information ◽

Brain Organization ◽

Network Nodes ◽

Different Types ◽

Definition Of ◽

And Function ◽

Specific Definition

Abstract Network models describe the brain as sets of nodes and edges that represent its distributed organization. So far, most discoveries in network neuroscience have prioritized insights that highlight distinct groupings and specialized functional contributions of network nodes. Importantly, these functional contributions are determined and expressed by the web of their interrelationships, formed by network edges. Here, we underscore the important contributions made by brain network edges for understanding distributed brain organization. Different types of edges represent different types of relationships, including connectivity and similarity among nodes. Adopting a specific definition of edges can fundamentally alter how we analyze and interpret a brain network. Furthermore, edges can associate into collectives and higher-order arrangements, describe time series, and form edge communities that provide insights into brain network topology complementary to the traditional node-centric perspective. Focusing on the edges, and the higher-order or dynamic information they can provide, discloses previously underappreciated aspects of structural and functional network organization.

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Research Malpractice and the Issue of Incidental Findings

The Journal of Law Medicine & Ethics ◽

10.1111/j.1748-720x.2008.00280.x ◽

2008 ◽

Vol 36 (2) ◽

pp. 356-360 ◽

Cited By ~ 22

Author(s):

Alan C. Milstein

Keyword(s):

Brain Function ◽

Neurological Status ◽

Speech Development ◽

Columbia University ◽

Brain Organization ◽

Physiological Basis ◽

Neurosurgical Planning ◽

Neurological Research ◽

Magnetic Resonance Imaging Mri ◽

And Function

Magnetic resonance imaging (MRI) and functional MRI (fMRI) are important tools for neuroscience research because of their capability for investigating both the structure and function of the brain. The fMRI image extends traditional anatomical imaging of the MRI to include maps of human brain function. The ability to observe brain function opens an array of opportunities to research brain organization, neurological status, and neurosurgical risk. Neurological research is, thus, burgeoning. For example, Columbia University currently has several ongoing protocols investigating fMRI’s future role in neurosurgical planning, pain management, and understanding the physiological basis for neurological disorders as well as cognitive and perceptual events. One can imagine research proposals, both important and trivial, on such topics as whether brain imaging can shed light on the nature of dreams, memory, speech development, love, anger, or addiction.

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