FND & the Brain
The brain operates on neural circuits (see The Brain & How It Talks To the Body), and the different symptoms of FND arise from one or more abnormal constructs, which can be mapped onto these various neural circuits. The research on this page is focused on the brain and body systems affected by FND, and is divided into sections by the year of publication. You can click on the title to go directly to the article/paper if you would like to read it. This page will be updated periodically as new information comes out, so be sure to check back for updates!
Note: As we look at the research and the various constructs involved, it is important to remember that the many brain areas work interactively together when evaluating and processing the information necessary for completing tasks, whether it is a thought or an action. If one area is 'malfunctioning', the message that is being relayed will likely be received incorrectly or not at all (see the Overview of FND page for a review).
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2023
The clinical management of functional neurological disorder: A scoping review of the literature (2023)
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Researchers, during a study in 2019, were able to predict functional seizures with over 90% accuracy based on neuropeptide Y and adrenocorticotropic hormone levels
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Another study found elevated levels of IL6, IL12, IL17A, IFNg, TNFa and lower levels of VEGF-a, suggesting systemic low-grade inflammation in motor FND
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microRNAs involved in inflammation and vascular inflammation were correlated with TNFa and VEGFa respectively, suggesting proof of concept for an epigenetic mechanism
2020
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Our intestinal microbiota includes bacteria, viruses, fungi, yeasts, and bacteriophages that start to develop at birth and continue for 2-3 years until it reaches a stable composition, but continues to be influenced by various environmental and lifestyle factors throughout the lifetime. Therefore, the microbiota composition differs remarkably even between healthy individuals. Under healthy conditions, the microbiota influences numerous physiological processes such as protection against pathogens, nutrient digestion and absorption, development, and education of multiple organs and the immune system.
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Studies revealed strong associations between changes in the microbiota composition (called dysbiosis) and various host diseases. Interestingly, among those, there are also diseases affecting host organs in physical distance from the gut, like the central nervous system (CNS). The communication between the CNS, the intestine, and the microbiota happens through the Gut-Brain Axis (GBA). Several neurotransmitters and metabolites such as essential vitamins, secondary bile acids, amino acids, and short-chain fatty acids (SCFAs), modulate many immune system pathways that in turn influence behavior, memory, learning, locomotion, and neurodegenerative disorders. Among those pathways, researchers showed that the inflammasome plays a role in depressive and anxiety-like behaviors, and locomotor activity.
A framework for understanding the pathophysiology of functional neurological disorder (2020)
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Abnormal constructs can be mapped onto specific brain circuits. constructs in FND include impairments in emotion processing, attention, interoception, predictive processing/inference, and their interactions. Abnormalities of these brain circuits (and constructs) interact in different ways to produce the signs and symptoms of FND.
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​Self-agency reflects a person’s belief that he or she is the agent of the action or thought—this is the sense of volition or free will that characterizes voluntary movement. ​
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Interoception refers to the process by which the nervous system senses, interprets, and integrates internal bodily signals, providing a moment-by-moment mapping of the body’s internal landscape across conscious and unconscious levels.
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2019
Three main processes have been implicated in the neurobiology of FND: abnormal attentional focus, beliefs and expectations about illness, and deficits in sense of self.
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Research has shown deficits in patients with FMD in movement that they had explicit, conscious control of, but no difference in performance of tasks that relied on automatic factors, suggesting that explicit movement may allow for increased attention on the production of movement in FMD.
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Patients with FMD tend to have a decreased sense of agency or control over their actions. One study compared brain activity in mimicked tremors and functional tremors in patients with FND; it found hypoactivity in the right temporoparietal junction and lower functional connectivity between the right temporoparietal junction, sensorimotor cortices and limbic regions during functional tremors, suggesting that symptoms are perceived to be involuntary despite the use of voluntary motor pathways.
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Several functional and structural abnormalities have consistently been present in patients with FND, especially in motor-processing regions and regions with dual motor and emotion processing functions. Compared with matched controls, patients with FNSD showed increased activity in the amygdala, supplementary motor area and periaqueductal gray matter (associated with the freeze response of fear) in response to negative emotions across several studies. Increased connectivity was demonstrated between the right amygdala and the right supplementary motor area when participants were presented with fearful and happy faces and in response to recall of stressful life events.
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Research has found abnormal functional connections in areas associated with cognitive control, behavioral inhibition and perceptual awareness. In patients with FND in response recall of stressful life events, enhanced activity has been found in the left dorsolateral prefrontal cortex, right supplementary motor area and temporoparietal junction, and decreased activity in the left hippocampus. Evidence also suggests abnormal brain activity in areas regulating sensory integration (posterior parietal cortex and angular gyrus regions).
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In terms of structural abnormalities, one study found no difference in insular volumes between patients with FND and controls. However, patients with FNSD who had self-reported severely impaired physical health had reduced left anterior insular gray matter volumes, and patients with FND participants who had self-reported severely impaired mental health had greater volumes of posterior-lateral cerebellar gray matter than controls. Two studies have demonstrated decreased gray matter volumes in the thalamus and basal ganglia in patients with FND. Further, another study found abnormal cortical atrophy in the right motor and premotor areas and the right and left cerebellum in patients with PNES. Structural abnormalities have also been found in children and adolescents with FND, demonstrating greater volume in the left supplementary motor area, right superior temporal gyrus and dorsomedial prefrontal cortex.​
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Some major themes found across several functional neuroimaging studies include: (1) heightened amygdalar reactivity to affectively valenced stimuli (something that catches your attention); (2) increased limbic/paralimbic-sensorimotor connectivity; (3) right temporoparietal junction/inferior parietal lobule hypoactivation and altered connectivity with sensorimotor cortices; (4) attentional dysregulation; and (5) deficits in motor planning, intention, execution, or inhibition. Other abnormalities include implicit attentional biases, perceptual-cognitive inferences, and mnemonic contributions to metacognitive processes disrupting subjective experience.
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FND frequently co-exists clinically with the somatic symptom disorders (SSD); a few FND studies reported comorbidities rates with somatoform disorders above 50%. Research has shown the functional neurobiology of SSD compared to healthy controls, which includes: (1) increased limbic, paralimbic (insula, parahippocampal), and striato-thalamic activity during noxious tactile stimuli; (2) decreased engagement of regulatory prefrontal regions during sensory and affective processing; (3) and sensorimotor, salience and default mode network resting-state alterations.
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In one study, 23 patients with PNES showed decreased bilateral inferior frontal, medial orbitofrontal, left caudal middle frontal, right precentral gyri and left insular surface area compared to controls; increased left posterior cingulate surface area was also observed in patients with PNES. Using machine learning, their MRI classification algorithm showed 75% accuracy in discriminating PNES from healthy subjects, with the inferior frontal, medial orbitofrontal and posterior cingulate cortices exhibiting the most differentiating profiles.
2016
Impaired resting vagal tone in patients with functional movement disorders (2016)
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vagal tone (an internal biological process that represents the activity of the vagus nerve) has been proposed as a physiological marker of stress vulnerability, with decreased resting vagal tone reflecting impaired ability of the individual to adapt appropriately to environmental demands
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FMD patients exhibit reduced resting vagal tone compared to healthy controls