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

Author(s):  
Justine Hansen ◽  
Golia Shafiei ◽  
Ross Markello ◽  
Kelly Smart ◽  
Sylvia Cox ◽  
...  

Abstract 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.

2021 ◽  
Author(s):  
Justine Y Hansen ◽  
Golia Shafiei ◽  
Ross D Markello ◽  
Kelly Smart ◽  
Sylvia ML Cox ◽  
...  

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.


2019 ◽  
Vol 26 (2) ◽  
pp. 117-133 ◽  
Author(s):  
Corey Horien ◽  
Abigail S. Greene ◽  
R. Todd Constable ◽  
Dustin Scheinost

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.


Author(s):  
Mark Woolrich ◽  
Mark Jenkinson ◽  
Clare Mackay

The brain is a highly complex system that is inaccessible to biopsy, which puts human brain imaging at the heart of our attempts to understand psychiatric disorders. Imaging has the potential to uncover the pathophysiology, provide biomarkers for use in the development and monitoring of treatments, and stratify patients for studies and trials. This chapter introduces the three main brain imaging technologies that are used to assay brain structure and function: magnetic resonance imaging (MRI), molecular imaging positron emission tomography (PET), and single-photon emission computed tomography (SPECT); electrophysiology [electroencephoaography (EEG)]; and magnetoencephalograpy (MEG). The chapter outlines the principles behind their use and the nature of the information that can be extracted. Together, these brain imaging methods can provide complementary windows into the living brain as an increasingly essential suite of tools for experimental medicine in psychiatry.


2015 ◽  
Vol 370 (1668) ◽  
pp. 20140171 ◽  
Author(s):  
Richard Frackowiak ◽  
Henry Markram

Cerebral cartography can be understood in a limited, static, neuroanatomical sense. Temporal information from electrical recordings contributes information on regional interactions adding a functional dimension. Selective tagging and imaging of molecules adds biochemical contributions. Cartographic detail can also be correlated with normal or abnormal psychological or behavioural data. Modern cerebral cartography is assimilating all these elements. Cartographers continue to collect ever more precise data in the hope that general principles of organization will emerge. However, even detailed cartographic data cannot generate knowledge without a multi-scale framework making it possible to relate individual observations and discoveries. We propose that, in the next quarter century, advances in cartography will result in progressively more accurate drafts of a data-led, multi-scale model of human brain structure and function. These blueprints will result from analysis of large volumes of neuroscientific and clinical data, by a process of reconstruction, modelling and simulation. This strategy will capitalize on remarkable recent developments in informatics and computer science and on the existence of much existing, addressable data and prior, though fragmented, knowledge. The models will instantiate principles that govern how the brain is organized at different levels and how different spatio-temporal scales relate to each other in an organ-centred context.


2021 ◽  
Author(s):  
Justine Y Hansen ◽  
Ross D Markello ◽  
Lauri Tuominen ◽  
Martin Norgaard ◽  
Elena Kuzmin ◽  
...  

Neurotransmitter receptors modulate the signaling between neurons. Thus, neurotransmitter receptors and transporters play a key role in shaping brain function. Due to the lack of comprehensive neurotransmitter receptor/transporter density datasets, microarray gene expression is often used as a proxy for receptor densities. In the present report, we comprehensively test the expression-density association for a total of 27 neurotransmitter receptors, receptor binding-sites, and transporters across 9 different neurotransmitter systems, using both PET and autoradiography imaging modalities. We find poor spatial correspondences between gene expression and density for all neurotransmitter receptors and transporters except four single-protein metabotropic receptors (5-HT1A, D2, CB1, and MOR). These expression-density associations are related to population variance and change across different classes of laminar differentiation. Altogether, we recommend using direct measures of receptor and transporter density when relating neurotransmitter systems to brain structure and function.


2021 ◽  
pp. 174-190
Author(s):  
Ingrid Agartz ◽  
Lynn Mørch-Johnsen

This chapter introduces structural neuroimaging methods and presents results from brain imaging studies of the clinical apathy syndrome in neurodegenerative diseases such as Alzheimer’s disease, mild cognitive impairment, Parkinson’s disease, Huntington’s disease, and stroke, and also in schizophrenia, today considered a neurodevelopmental disease. The main method used has been magnetic resonance imaging, which also holds many innovative possibilities for future development. Scientific studies so far have pointed to structural differences in frontal, striatal, anterior cingulate, and parietal brain regions, and of white matter microstructure and connectivity changes as being involved in the apathy syndrome. No single circuit connected to apathy has so far been identified. Brain structure and function, studied at the systems network level, and integrative multimodal imaging approaches, which combine different high-resolution magnetic resonance imaging, magnetic resonance diffusion, and positron emission tomography techniques, can be helpful in resolving future questions.


2013 ◽  
Vol 109 (5) ◽  
pp. 1444-1456 ◽  
Author(s):  
B. J. Shannon ◽  
R. A. Dosenbach ◽  
Y. Su ◽  
A. G. Vlassenko ◽  
L. J. Larson-Prior ◽  
...  

It has been posited that a critical function of sleep is synaptic renormalization following a net increase in synaptic strength during wake. We hypothesized that wake would alter the resting-state functional organization of the brain and increase its metabolic cost. To test these hypotheses, two experiments were performed. In one, we obtained morning and evening resting-state functional MRI scans to assess changes in functional brain organization. In the second experiment, we obtained quantitative positron emission tomography measures of glucose and oxygen consumption to assess the cost of wake. We found selective changes in brain organization. Most prominently, bilateral medial temporal regions were locally connected in the morning but in the evening exhibited strong correlations with frontal and parietal brain regions involved in memory retrieval. We speculate that these changes may reflect aspects of memory consolidation recurring on a daily basis. Surprisingly, these changes in brain organization occurred without increases in brain metabolism.


2019 ◽  
Author(s):  
Franziskus Liem ◽  
Linda Geerligs ◽  
Jessica S. Damoiseaux ◽  
Daniel S. Margulies

A large body of research shows that aging is accompanied by localized changes in brain structure and function. However, over the past decade the neuroimaging community has begun to recognize the importance of investigating the brain as a network. Brain regions don’t function independently, rather they form an expansive network that allows for communication between distant areas and enables complex cognitive functioning. Hence, age-related changes in the network structure might explain changes in cognitive functioning.Characterizing this network by investigating the brain’s functional connectivity has enabled new insights into brain organization. In this chapter, we will outline how the brain’s functional connectivity is affected by aging and how changes in functional connectivity relate to changes in cognitive functioning. We will address how neurodegenerative pathology influences functional connectivity and how, based on these measurements, biomarkers for clinical outcome might be developed in the future.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chia-Chun Hung ◽  
Yi-Hsuan Liu ◽  
Chu-Chung Huang ◽  
Cheng-Ying Chou ◽  
Chun-Ming Chen ◽  
...  

Abstract Ketamine has been used for medical purposes, most typically as an anesthetic, and recent studies support its use in the treatment of depression. However, ketamine tends to be abused by adolescents and young adults. In the current study, we examined the effects of early ketamine exposure on brain structure and function. We employed MRI to assess the effects of ketamine abuse on cerebral gray matter volume (GMV) and functional connectivity (FC) in 34 users and 19 non-users, employing covariates. Ketamine users were categorized as adolescent-onset and adult-onset based on when they were first exposed to ketamine. Imaging data were processed by published routines in SPM and AFNI. The results revealed lower GMV in the left precuneus in ketamine users, with a larger decrease in the adolescent-onset group. The results from a seed-based correlation analysis show that both ketamine groups had higher functional connectivity between left precuneus (seed) and right precuneus than the control group. Compared to controls, ketamine users showed decreased GMV in the right insula, left inferior parietal lobule, left dorsolateral prefrontal cortex/superior frontal gyrus, and left medial orbitofrontal cortex. These preliminary results characterize the effects of ketamine misuse on brain structure and function and highlight the influence of earlier exposure to ketamine on the development of the brain. The precuneus, a structure of central importance to cerebral functional organization, may be particularly vulnerable to the influences of early ketamine exposure. How these structural and functional brain changes may relate to the cognitive and affective deficits remains to be determined with a large cohort of participants.


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