The dysfunctome is a proposed conceptual framework [2] that describes a library of circuits that may become dysfunctional in the human brain as a consequence of various brain disorders. [3] [4] [5] Analogous to terms like the genome (the total genetic information of an organism), the proteome (the entire set of proteins expressed) and the connectome (the parts of the entire brain and their interconnections) the dysfunctome aims to map out how disruptions—of whichever nature—contribute to disease states and pathological signs or symptoms if specific brain circuits become dysfunctional.
An increasingly adopted view is that many symptoms of neurological or psychiatric diseases originate from brain circuit dysfunctions, which have also been termed 'oscillopathies' [6] or 'disorders of the connectome'. [7] Indeed, evidence accumulates, that the same circuit may be responsible for the same symptom as expressed by patients with different diseases. Examples include a dysfunctional circuit between cerebellar nuclei, the cerebellar receiving thalamus and primary motor cortex, which has been associated with various forms of tremor in disorders such as Parkinson's Disease, Essential Tremor, Multiple Sclerosis and other disorders. [8] Similarly, a common circuit involved in obsessive compulsive behavior has been identified to play a role in OCD and Tourette's Syndrome. [9]
Finally, a shared polysynaptic brain network has been associated with the occurrence of depression in Major depression, epilepsy and Parkinson's Disease. [10] This transnosologic view, which associates brain circuit disruption with symptoms, rather with disorders, is also reflected by the Research Domain Criteria (RDoC) concept by the National Institutes of Mental Health. [11] [12]
In this light, the hypothetical concept of the dysfunctome aims at constructing an exhaustive library that maps circuits, which, when dysfunctional, will lead to a given neurological or psychiatric symptom. Critically, the concept does not specify the nature of the dysfunction, which could include hyper-/hypoactivity, loss of sensible information processing, microseizures or other disruptions that could unfold along brain circuits. [13]
The term “dysfunctome” combines “dysfunction,” referring to the impaired or abnormal functioning of processes, with the suffix “-ome,” commonly used to denote a totality or complete set (e.g., genome, metabolome, microbiome). [14] The concept underscores the importance of comprehensive, system-wide approaches to understanding diseases, moving beyond the study of individual brain circuits or individual pathological symptoms. [15]
Deep brain stimulation (DBS) is a surgical procedure that implants a neurostimulator and electrodes which sends electrical impulses to specified targets in the brain responsible for movement control. The treatment is designed for a range of movement disorders such as Parkinson's disease, essential tremor, and dystonia, as well as for certain neuropsychiatric conditions like obsessive-compulsive disorder (OCD) or neurological disorders like epilepsy. The exact mechanisms of DBS are complex and not entirely clear, but it is known to modify brain activity in a structured way.
Neurotechnology encompasses any method or electronic device which interfaces with the nervous system to monitor or modulate neural activity.
Intention tremor is a dyskinetic disorder characterized by a broad, coarse, and low-frequency tremor evident during deliberate and visually-guided movement. An intention tremor is usually perpendicular to the direction of movement. When experiencing an intention tremor, one often overshoots or undershoots one's target, a condition known as dysmetria. Intention tremor is the result of dysfunction of the cerebellum, particularly on the same side as the tremor in the lateral zone, which controls visually guided movements. Depending on the location of cerebellar damage, these tremors can be either unilateral or bilateral.
A connectome is a comprehensive map of neural connections in the brain, and may be thought of as its "wiring diagram". An organism's nervous system is made up of neurons which communicate through synapses. A connectome is constructed by tracing the neuron in a nervous system and mapping where neurons are connected through synapses.
Responsive neurostimulation device is a medical device that senses changes in a person's body and uses neurostimulation to respond in the treatment of disease. The FDA has approved devices for use in the United States in the treatment of epileptic seizures and chronic pain conditions. Devices are being studied for use in the treatment of essential tremor, Parkinson's disease, Tourette's syndrome, depression, obesity, and post-traumatic stress disorder.
Connectomics is the production and study of connectomes: comprehensive maps of connections within an organism's nervous system. More generally, it can be thought of as the study of neuronal wiring diagrams with a focus on how structural connectivity, individual synapses, cellular morphology, and cellular ultrastructure contribute to the make up of a network. The nervous system is a network made of up to billions of connections and these connections are responsible for our thoughts, emotions, actions, memories, function and dysfunction. Therefore, the study of connectomics aims to advance our understanding of mental health and cognition by understanding how cells in the nervous system are connected and communicate. Because these structures are extremely complex, methods within this field use a high-throughput application of functional and structural neural imaging, most commonly magnetic resonance imaging (MRI), electron microscopy, and histological techniques in order to increase the speed, efficiency, and resolution of these nervous system maps. To date, tens of large scale datasets have been collected spanning the nervous system including the various areas of cortex, cerebellum, the retina, the peripheral nervous system and neuromuscular junctions.
Myoclonic dystonia or Myoclonus dystonia syndrome is a rare movement disorder that induces spontaneous muscle contraction causing abnormal posture. The prevalence of myoclonus dystonia has not been reported, however, this disorder falls under the umbrella of movement disorders which affect thousands worldwide. Myoclonus dystonia results from mutations in the SGCE gene coding for an integral membrane protein found in both neurons and muscle fibers. Those suffering from this disease exhibit symptoms of rapid, jerky movements of the upper limbs (myoclonus), as well as distortion of the body's orientation due to simultaneous activation of agonist and antagonist muscles (dystonia).
Neurogenomics is the study of how the genome of an organism influences the development and function of its nervous system. This field intends to unite functional genomics and neurobiology in order to understand the nervous system as a whole from a genomic perspective.
The Human Connectome Project (HCP) is a five-year project sponsored by sixteen components of the National Institutes of Health, split between two consortia of research institutions. The project was launched in July 2009 as the first of three Grand Challenges of the NIH's Blueprint for Neuroscience Research. On September 15, 2010, the NIH announced that it would award two grants: $30 million over five years to a consortium led by Washington University in St. Louis and the University of Minnesota, with strong contributions from University of Oxford (FMRIB) and $8.5 million over three years to a consortium led by Harvard University, Massachusetts General Hospital and the University of California Los Angeles.
The cortico-basal ganglia-thalamo-cortical loop is a system of neural circuits in the brain. The loop involves connections between the cortex, the basal ganglia, the thalamus, and back to the cortex. It is of particular relevance to hyperkinetic and hypokinetic movement disorders, such as Parkinson's disease and Huntington's disease, as well as to mental disorders of control, such as attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), and Tourette syndrome.
The salience network (SN), also known anatomically as the midcingulo-insular network (M-CIN) or ventral attention network, is a large scale network of the human brain that is primarily composed of the anterior insula (AI) and dorsal anterior cingulate cortex (dACC). It is involved in detecting and filtering salient stimuli, as well as in recruiting relevant functional networks. Together with its interconnected brain networks, the SN contributes to a variety of complex functions, including communication, social behavior, and self-awareness through the integration of sensory, emotional, and cognitive information.
Morten L Kringelbach is a professor of neuroscience at University of Oxford, UK and Aarhus University, Denmark. He is the director of the 'Centre for Eudaimonia and Human Flourishing', fellow of Linacre College, Oxford and board member of the Empathy Museum.
Maryam M. Shanechi is an Iran-born American neuroengineer. She studies ways of decoding the brain's activity to control brain-machine interfaces. She was honored as one of MIT Technology Review's Innovators under 35 in 2014, one of the Science News 10 scientists to watch in 2019, and a National Finalist for the Blavatnik Awards for Young Scientists in 2023. She is Dean's Professor in Electrical and Computer Engineering, Computer Science, and Biomedical Engineering at the USC Viterbi School of Engineering, and a member of the Neuroscience Graduate Program at the University of Southern California.
Camilla Bellone is an Italian neuroscientist and assistant professor in the Department of Basic Neuroscience at the University of Geneva, in Switzerland. Bellone's laboratory explores the molecular mechanisms and neural circuits underlying social behavior and probes how defects at the molecular and circuit level give rise to psychiatric disease states such as Autism Spectrum Disorders.
Polina Olegovna Anikeeva is a Russian-born American materials scientist who is a Professor of Material Science & Engineering as well as Brain & Cognitive Sciences at the Massachusetts Institute of Technology (MIT). She also holds faculty appointments in the McGovern Institute for Brain Research and Research Laboratory of Electronics at MIT. Her research is centered on developing tools for studying the underlying molecular and cellular bases of behavior and neurological diseases. She was awarded the 2018 Vilcek Foundation Prize for Creative Promise in Biomedical Science, the 2020 MacVicar Faculty Fellowship at MIT, and in 2015 was named a MIT Technology Review Innovator Under 35.
There is increasing evidence suggesting that COVID-19 causes both acute and chronic neurologicalor psychological symptoms. Caregivers of COVID-19 patients also show a higher than average prevalence of mental health concerns. These symptoms result from multiple different factors.
Elaine Yih-Nien Hsiao is an American biologist who is Professor in Biological Sciences at University of California, Los Angeles. Her research considers the microbes that impact human health. She was a 2022 Laureate for the Blavatnik Awards for Young Scientists.
Michael D. Fox is an American neurologist and Professor of Neurology at Harvard Medical School where he holds the Raymond D. Adams Distinguished Chair in Neurology and directs the Center for Brain Circuit Therapeutics at Brigham and Women's Hospital. His research has focused on resting state brain fMRI which uses spontaneous fluctuations in blood oxygenation to map brain networks including the default mode network. He developed the technique lesion network mapping to study the connectivity patterns of brain lesions to help understand the neuroanatomy of a diverse range of processes including addiction, criminality, blindsight, free will and religiosity. Fox has been considered among the "World's Most Influential Scientific Minds" by Thomson Reuters since 2014.
Andreas Horn is a German neuroscientist and Associate Professor of Neurology at Harvard Medical School and Mass General Brigham. His research has focused on mapping deep brain stimulation outcomes onto networks of the human brain. Horn's work has been featured by media outlets such as CNN, Newsweek or Fox News and he has been considered among the 'World's Highly Cited Researchers' by Clarivate.