Dysfunctome

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Fiber bundles that are dysfunctional and when suppressed associated with symptom improvement following deep brain stimulation in Parkinson's disease (green), dystonia (yellow), Tourette's syndrome (blue), and obsessive-compulsive disorder (red). Dysfunctome.png
Fiber bundles that are dysfunctional and when suppressed associated with symptom improvement following deep brain stimulation in Parkinson’s disease (green), dystonia (yellow), Tourette’s syndrome (blue), and obsessive-compulsive disorder (red).

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.

Contents

Description

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]

Etymology

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]

See also

Related Research Articles

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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.

<span class="mw-page-title-main">Connectome</span> Comprehensive map of neural connections in the brain

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.

<span class="mw-page-title-main">Responsive neurostimulation device</span> Category of medical devices that respond to signals in a patients body to treat disease

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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).

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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.

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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.

<span class="mw-page-title-main">Polina Anikeeva</span> Russian-American materials scientist

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References

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