-
Nature Reviews. Neuroscience Sep 2013Mood disorders are common and debilitating conditions characterized in part by profound deficits in reward-related behavioural domains. A recent literature has... (Review)
Review
Mood disorders are common and debilitating conditions characterized in part by profound deficits in reward-related behavioural domains. A recent literature has identified important structural and functional alterations within the brain's reward circuitry--particularly in the ventral tegmental area-nucleus accumbens pathway--that are associated with symptoms such as anhedonia and aberrant reward-associated perception and memory. This Review synthesizes recent data from human and rodent studies from which emerges a circuit-level framework for understanding reward deficits in depression. We also discuss some of the molecular and cellular underpinnings of this framework, ranging from adaptations in glutamatergic synapses and neurotrophic factors to transcriptional and epigenetic mechanisms.
Topics: Animals; Brain; Humans; Mood Disorders; Neural Pathways; Reward
PubMed: 23942470
DOI: 10.1038/nrn3381 -
Physics of Life Reviews Mar 2014The nature of consciousness, the mechanism by which it occurs in the brain, and its ultimate place in the universe are unknown. We proposed in the mid 1990's that... (Review)
Review
The nature of consciousness, the mechanism by which it occurs in the brain, and its ultimate place in the universe are unknown. We proposed in the mid 1990's that consciousness depends on biologically 'orchestrated' coherent quantum processes in collections of microtubules within brain neurons, that these quantum processes correlate with, and regulate, neuronal synaptic and membrane activity, and that the continuous Schrödinger evolution of each such process terminates in accordance with the specific Diósi-Penrose (DP) scheme of 'objective reduction' ('OR') of the quantum state. This orchestrated OR activity ('Orch OR') is taken to result in moments of conscious awareness and/or choice. The DP form of OR is related to the fundamentals of quantum mechanics and space-time geometry, so Orch OR suggests that there is a connection between the brain's biomolecular processes and the basic structure of the universe. Here we review Orch OR in light of criticisms and developments in quantum biology, neuroscience, physics and cosmology. We also introduce a novel suggestion of 'beat frequencies' of faster microtubule vibrations as a possible source of the observed electro-encephalographic ('EEG') correlates of consciousness. We conclude that consciousness plays an intrinsic role in the universe.
Topics: Animals; Brain; Consciousness; Humans; Neurons; Quantum Theory
PubMed: 24070914
DOI: 10.1016/j.plrev.2013.08.002 -
International Journal of Molecular... Feb 2022Globally, the incidence of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) epidemics is increasing rapidly and has huge financial and emotional costs. The... (Review)
Review
Globally, the incidence of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) epidemics is increasing rapidly and has huge financial and emotional costs. The purpose of the current review article is to discuss the shared pathophysiological connections between AD and T2DM. Research findings are presented to underline the vital role that insulin plays in the brain's neurotransmitters, homeostasis of energy, as well as memory capacity. The findings of this review indicate the existence of a mechanistic interplay between AD pathogenesis with T2DM and, especially, disrupted insulin signaling. AD and T2DM are interlinked with insulin resistance, neuroinflammation, oxidative stress, advanced glycosylation end products (AGEs), mitochondrial dysfunction and metabolic syndrome. Beta-amyloid, tau protein and amylin can accumulate in T2DM and AD brains. Given that the T2DM patients are not routinely evaluated in terms of their cognitive status, they are rarely treated for cognitive impairment. Similarly, AD patients are not routinely evaluated for high levels of insulin or for T2DM. Studies suggesting AD as a metabolic disease caused by insulin resistance in the brain also offer strong support for the hypothesis that AD is a type 3 diabetes.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Brain; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Resistance
PubMed: 35269827
DOI: 10.3390/ijms23052687 -
Physiological Reviews Jan 2023Studies of the choroid plexus lag behind those of the more widely known blood-brain barrier, despite a much longer history. This review has two overall aims. The first... (Review)
Review
Studies of the choroid plexus lag behind those of the more widely known blood-brain barrier, despite a much longer history. This review has two overall aims. The first is to outline long-standing areas of research where there are unanswered questions, such as control of cerebrospinal fluid (CSF) secretion and blood flow. The second aim is to review research over the past 10 years where the focus has shifted to the idea that there are choroid plexuses located in each of the brain's ventricles that make specific contributions to brain development and function through molecules they generate for delivery via the CSF. These factors appear to be particularly important for aspects of normal brain growth. Most research carried out during the twentieth century dealt with the choroid plexus, a brain barrier interface making critical contributions to the composition and stability of the brain's internal environment throughout life. More recent research in the twenty-first century has shown the importance of choroid plexus-generated CSF in neurogenesis, influence of sex and other hormones on choroid plexus function, and choroid plexus involvement in circadian rhythms and sleep. The advancement of technologies to facilitate delivery of brain-specific therapies via the CSF to treat neurological disorders is a rapidly growing area of research. Conversely, understanding the basic mechanisms and implications of how maternal drug exposure during pregnancy impacts the developing brain represents another key area of research.
Topics: Humans; Choroid Plexus; Blood-Brain Barrier; Brain; Biological Transport; Cerebral Ventricles
PubMed: 36173801
DOI: 10.1152/physrev.00060.2021 -
Nature Apr 2014Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales....
Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales. However, with the singular exception of the C. elegans microscale connectome, there are no complete connectivity data sets in other species. Here we report a brain-wide, cellular-level, mesoscale connectome for the mouse. The Allen Mouse Brain Connectivity Atlas uses enhanced green fluorescent protein (EGFP)-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain. This systematic and standardized approach allows spatial registration of individual experiments into a common three dimensional (3D) reference space, resulting in a whole-brain connectivity matrix. A computational model yields insights into connectional strength distribution, symmetry and other network properties. Virtual tractography illustrates 3D topography among interconnected regions. Cortico-thalamic pathway analysis demonstrates segregation and integration of parallel pathways. The Allen Mouse Brain Connectivity Atlas is a freely available, foundational resource for structural and functional investigations into the neural circuits that support behavioural and cognitive processes in health and disease.
Topics: Animals; Atlases as Topic; Axons; Brain; Cerebral Cortex; Connectome; Corpus Striatum; Male; Mice; Mice, Inbred C57BL; Models, Neurological; Neuroanatomical Tract-Tracing Techniques; Thalamus
PubMed: 24695228
DOI: 10.1038/nature13186 -
NeuroImage Jan 2019Understanding complex systems such as the human brain requires characterization of the system's architecture across multiple levels of organization - from neurons, to...
Understanding complex systems such as the human brain requires characterization of the system's architecture across multiple levels of organization - from neurons, to local circuits, to brain regions, and ultimately large-scale brain networks. Here we focus on characterizing the human brain's large-scale network organization, as it provides an overall framework for the organization of all other levels. We developed a highly principled approach to identify cortical network communities at the level of functional systems, calibrating our community detection algorithm using extremely well-established sensory and motor systems as guides. Building on previous network partitions, we replicated and expanded upon well-known and recently-identified networks, including several higher-order cognitive networks such as a left-lateralized language network. We expanded these cortical networks to subcortex, revealing 358 highly-organized subcortical parcels that take part in forming whole-brain functional networks. Notably, the identified subcortical parcels are similar in number to a recent estimate of the number of cortical parcels (360). This whole-brain network atlas - released as an open resource for the neuroscience community - places all brain structures across both cortex and subcortex into a single large-scale functional framework, with the potential to facilitate a variety of studies investigating large-scale functional networks in health and disease.
Topics: Brain; Connectome; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Nerve Net
PubMed: 30291974
DOI: 10.1016/j.neuroimage.2018.10.006 -
Neuroscience and Biobehavioral Reviews Aug 2019The role of peripheral physiology in the experience of emotion has been debated since the 19th century following the seminal proposal by William James that somatic... (Review)
Review
The role of peripheral physiology in the experience of emotion has been debated since the 19th century following the seminal proposal by William James that somatic responses to stimuli determine subjective emotion. Subsequent views have integrated the forebrain's ability to initiate, represent and simulate such physiological events. Modern affective neuroscience envisions an interacting network of "bottom-up" and "top-down" signaling in which the peripheral (PNS) and central nervous systems both receive and generate the experience of emotion. "Feelings" serves as a term for the perception of these physical changes whether emanating from actual somatic events or from the brain's representation of such. "Interoception" has come to represent the brain's receipt and representation of these actual and "virtual" somatic changes that may or may not enter conscious awareness but, nonetheless, influence feelings. Such information can originate from diverse sources including endocrine, immune and gastrointestinal systems as well as the PNS. We here examine physiological feelings from diverse perspectives including current and historical theories, evolution, neuroanatomy and physiology, development, regulatory processes, pathology and linguistics.
Topics: Autonomic Nervous System; Brain; Emotional Regulation; Emotions; Evoked Potentials; Humans; Hypothalamo-Hypophyseal System; Interoception; Stress, Psychological
PubMed: 31125635
DOI: 10.1016/j.neubiorev.2019.05.002 -
Neuron Nov 2022The emerging understanding of homeostatic neuroimmune interactions requires developing relevant terminology. In this NeuroView, Koren and Rolls define "immunoception" as...
The emerging understanding of homeostatic neuroimmune interactions requires developing relevant terminology. In this NeuroView, Koren and Rolls define "immunoception" as the brain's bidirectional monitoring and control of immunity. They propose that the physiological trace storing immune-related information, the "immunengram," is distributed between the brain and memory cells residing in peripheral tissues.
Topics: Brain; Neuroimmunomodulation; Homeostasis
PubMed: 36327893
DOI: 10.1016/j.neuron.2022.10.016 -
Nature Jun 2023The anatomy of the brain necessarily constrains its function, but precisely how remains unclear. The classical and dominant paradigm in neuroscience is that neuronal...
The anatomy of the brain necessarily constrains its function, but precisely how remains unclear. The classical and dominant paradigm in neuroscience is that neuronal dynamics are driven by interactions between discrete, functionally specialized cell populations connected by a complex array of axonal fibres. However, predictions from neural field theory, an established mathematical framework for modelling large-scale brain activity, suggest that the geometry of the brain may represent a more fundamental constraint on dynamics than complex interregional connectivity. Here, we confirm these theoretical predictions by analysing human magnetic resonance imaging data acquired under spontaneous and diverse task-evoked conditions. Specifically, we show that cortical and subcortical activity can be parsimoniously understood as resulting from excitations of fundamental, resonant modes of the brain's geometry (that is, its shape) rather than from modes of complex interregional connectivity, as classically assumed. We then use these geometric modes to show that task-evoked activations across over 10,000 brain maps are not confined to focal areas, as widely believed, but instead excite brain-wide modes with wavelengths spanning over 60 mm. Finally, we confirm predictions that the close link between geometry and function is explained by a dominant role for wave-like activity, showing that wave dynamics can reproduce numerous canonical spatiotemporal properties of spontaneous and evoked recordings. Our findings challenge prevailing views and identify a previously underappreciated role of geometry in shaping function, as predicted by a unifying and physically principled model of brain-wide dynamics.
Topics: Humans; Axons; Brain; Brain Mapping; Magnetic Resonance Imaging; Neurons
PubMed: 37258669
DOI: 10.1038/s41586-023-06098-1 -
Cell Stem Cell Oct 2013A major barrier in understanding nervous system development is modeling the cellular interactions that form the human brain. Recently, in the journal Nature, Lancaster...
A major barrier in understanding nervous system development is modeling the cellular interactions that form the human brain. Recently, in the journal Nature, Lancaster et al. (2013) established a protocol for culturing pluripotent stem cell (PSC)-derived "cerebral organoids" that mimics the developing human brain's cellular organization, segregates into distinct brain regions, and models microcephaly.
Topics: Animals; Brain; Humans; Microcephaly; Models, Biological; Organoids; Tissue Culture Techniques
PubMed: 24094317
DOI: 10.1016/j.stem.2013.09.010