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Article: Predictive Processing and the Pathophysiology of Functional Neurological Disorder.

Jungilligens, Johannes / Perez, David L

Current topics in behavioral neurosciences

2024

Abstract: The contemporary neuroscience understanding of the brain as an active inference organ supports that our conscious experiences, including sensorimotor perceptions, depend on the integration of probabilistic predictions with incoming sensory input across ... ...

Abstract	The contemporary neuroscience understanding of the brain as an active inference organ supports that our conscious experiences, including sensorimotor perceptions, depend on the integration of probabilistic predictions with incoming sensory input across hierarchically organized levels. As in other systems, these complex processes are prone to error under certain circumstances, which may lead to alterations in their outcomes (i.e., variations in sensations and movements). Such variations are an important aspect of functional neurological disorder, a complex disorder at the interface of brain-mind-body interactions. Thus, predictive processing frameworks offer fundamental mechanistic insights into the pathophysiology of functional neurological disorder. In recent years, many of the aspects relevant to the neurobiology of functional neurological disorder - e.g., aberrant motor and sensory processes, symptom expectation, self-agency, and illness beliefs, as well as interoception, allostasis, and emotion - have been investigated through the lens of predictive processing frameworks. Here, we provide an overview of the current state of research on predictive processing and the pathophysiology of functional neurological disorder.
Language	English
Publishing date	2024-05-17
Publishing country	Germany
Document type	Journal Article
ISSN	1866-3370
ISSN	1866-3370
DOI	10.1007/7854_2024_473
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Article ; Online: Funktionelle Bewegungsstörungen verstehen und verständlich machen.

Popkirov, Stoyan / Jungilligens, Johannes / Michaelis, Rosa

Der Nervenarzt

2024

Abstract: Functional movement disorders are not uncommon in neurological consultations, hospitals and emergency departments. Although the disorder can usually be recognized clinically, the communication of the diagnosis is often unsatisfactory. Those affected are ... ...

Title translation	Understanding and explaining functional movement disorders.
Abstract	Functional movement disorders are not uncommon in neurological consultations, hospitals and emergency departments. Although the disorder can usually be recognized clinically, the communication of the diagnosis is often unsatisfactory. Those affected are indirectly accused of a lack of insight or openness but it is often the doctors who fail to formulate a coherent and comprehensible explanation of the underlying disorder. In this review an integrative model for the development of functional movement disorders is presented, which places the motor (and nonmotor) symptoms in a neuroscientific light. In addition, explanations and metaphors are presented that have proven helpful in conveying an understanding of the disorder.
Language	German
Publishing date	2024-02-16
Publishing country	Germany
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	123291-5
ISSN	1433-0407 ; 0028-2804
ISSN (online)	1433-0407
ISSN	0028-2804
DOI	10.1007/s00115-024-01619-3
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Book ; Thesis: Emotion processing and metacognition in patients with dissociative seizures. Clinical importance and neural underpinnings

Jungilligens, Johannes

2020

Abstract: Dissociative seizures are brief episodes of altered awareness and behavioural control which are assumed to be of psychological origin. In this dissertation, emotion processing and metacognitive functions in patients with dissociative seizures are ... ...

Title translation	Emotionsverarbeitung und Metakognition bei Patienten mit dissoziativen Anfällen - Klinische Bedeutsamkeit und neuronale Untermauerung
Abstract	Dissociative seizures are brief episodes of altered awareness and behavioural control which are assumed to be of psychological origin. In this dissertation, emotion processing and metacognitive functions in patients with dissociative seizures are investigated using an experimental-behavioural approach, self-report questionnaires, and high-quality diffusion tensor imaging. We found impairments in emotion processing in patients with dissociative seizures, which were correlated with the microstructural integrity of distinctive brain networks. The microstructural integrity of these networks was furthermore related both to traumatic experiences and to the clinical manifestation of the disorder. These findings and their comprehensive integration across multiple levels provide a more detailed knowledge on key pathomechanistic factors and might enable scientists, clinicians, and affected patients to gain a deeper understanding of this debilitating illness. - Contents: (1) Popkirov, S., Jungilligens, J., Schlegel, U. & Wellmer, J. (2018). Research on dissociative seizures: A bibliometric analysis and visualization of the scientific landscape. Epilepsy & Behavior, 83, 162-167. DOI: 10.1016/j.yebeh.2018.03.041. (2) Popkirov, S., Jungilligens, J., Grönheit, W. & Wellmer, J. (2017). Diagnosing psychogenic nonepileptic seizures: Video-EEG monitoring, suggestive seizure induction and diagnostic certainty. Epilepsy & Behavior, 73, 54-58. DOI: 10.1016/j.yebeh.2017.05.027. (3) Jungilligens, J., Wellmer, J., Schlegel, U., Kessler, H., Axmacher, N. & Popkirov, S. (2019). Impaired emotional and behavioural awareness and control in patients with dissociative seizures. Psychological Medicine, 1-9. DOI: 10.1017/S0033291719002861. (4) Jungilligens, J., Wellmer, J., Kowoll, A., Schlegel, U., Axmacher, N. & Popkirov, S. (n. d.). Affective neurocircuitry varies with illness severity and trauma in dissociative seizures. Manuscript submitted for publication.
Keywords	Anfälle ; Awareness ; Bewusstheit ; Biological Neural Networks ; Biologische Neuronale Netze ; Diffusion Tensor Imaging ; Diffusions-Tensor-Bildgebung ; Dissociation ; Dissoziation ; Emotionen ; Emotions ; Metacognition ; Metakognition ; Seizures
Language	English
Size	170 pp., 9 pp. appendix
Publisher	Universität, Fakultät für Psychologie
Publishing place	Bochum
Document type	Book ; Thesis
Note	Elektronische Publikation im Internet. Kumulative Dissertation
DOI	10.13154/294-7471
Database	PSYNDEX

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Article ; Online: Dissociative seizures in the emergency room: room for improvement.

Cengiz, Ozan / Jungilligens, Johannes / Michaelis, Rosa / Wellmer, Jörg / Popkirov, Stoyan

Journal of neurology, neurosurgery, and psychiatry

2024 Volume 95, Issue 4, Page(s) 294–299

Abstract: Background: Dissociative seizures, also known as functional or psychogenic non-epileptic seizures, account for 11%-27% of all emergency seizure presentations. Misdiagnosis as epileptic seizures is common and leads to ineffective and potentially harmful ... ...

Abstract	Background: Dissociative seizures, also known as functional or psychogenic non-epileptic seizures, account for 11%-27% of all emergency seizure presentations. Misdiagnosis as epileptic seizures is common and leads to ineffective and potentially harmful treatment escalations. We assess the potential for diagnostic improvement at different stages of emergency workup and estimate the utility of benzodiazepines. Methods: A retrospective study of all emergency presentations with a discharge diagnosis of acute dissociative seizures seen at a university hospital 2010-2022 was performed to assess clinical characteristics and emergency decision-making. Results: Among 156 patients (73% female, median 29 years), 15% presented more than once for a total of 203 presentations. Half of seizures were ongoing at first medical contact; prolonged seizures and clusters were common (23% and 24%). Diagnostic accuracy differed between on-site emergency physicians and emergency department neurologists (12% vs 52%). Typical features such as eye closure, discontinuous course and asynchronous movements were common. Benzodiazepines were given in two-thirds of ongoing seizures, often in high doses and preferentially for major hyperkinetic semiology. Clinical response to benzodiazepines was mixed, with a minority of patients remaining either unaffected (16%) or becoming critically sedated (13%). A quarter of patients given benzodiazepines by emergency medical services were admitted to a monitoring unit, 9% were intubated. Conclusions: Improved semiological assessment could reduce early misdiagnosis of dissociative seizures. Although some seizures seem to respond to benzodiazepines, critical sedation is common, and further studies are needed to assess the therapeutic ratio.
MeSH term(s)	Humans ; Female ; Male ; Retrospective Studies ; Psychogenic Nonepileptic Seizures ; Seizures ; Emergency Service, Hospital ; Benzodiazepines/therapeutic use ; Electroencephalography
Chemical Substances	Benzodiazepines (12794-10-4)
Language	English
Publishing date	2024-03-13
Publishing country	England
Document type	Journal Article
ZDB-ID	3087-9
ISSN	1468-330X ; 0022-3050
ISSN (online)	1468-330X
ISSN	0022-3050
DOI	10.1136/jnnp-2023-332063
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Article ; Online: Misdiagnosis of prolonged psychogenic non-epileptic seizures as status epilepticus: epidemiology and associated risks.

Jungilligens, Johannes / Michaelis, Rosa / Popkirov, Stoyan

Journal of neurology, neurosurgery, and psychiatry

2021 Volume 92, Issue 12, Page(s) 1341–1345

Abstract: Objective: To determine the epidemiology of prolonged psychogenic non-epileptic seizures (pPNES) misdiagnosed as status epilepticus, as well as the risks associated with non-indicated treatment.: Methods: We performed an individual patient data ... ...

Abstract	Objective: To determine the epidemiology of prolonged psychogenic non-epileptic seizures (pPNES) misdiagnosed as status epilepticus, as well as the risks associated with non-indicated treatment. Methods: We performed an individual patient data analysis from the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) and the Established Status Epilepticus Treatment Trial (ESETT) to assess incidence, patient characteristics and clinical course of misdiagnosed pPNES. Results: Among 980 patients aged 8 years or older diagnosed and treated for status epilepticus in RAMPART and ESETT, 79 (8.1%) were discharged with a final diagnosis of pPNES. The relative incidence was highest in adolescents and young adults (20.1%). The typical female preponderance seen in that age bracket was not evident in children and older adults. Adverse effects, including respiratory depression and intubation, were documented in 26% of patients with pPNES receiving benzodiazepines in RAMPART and 33% of patients receiving additional second-line medication in ESETT. In ESETT, patients who were treated with benzodiazepines before hospital admission had higher rates of unresponsiveness and severe adverse effects than those treated after admission, suggesting cumulative effects of accelerated treatment momentum. Across trials, one in five patients with pPNES were admitted to an intensive care unit. Conclusions: Misdiagnosis and treatment of pPNES as status epilepticus are a common and widespread problem with deleterious consequences. Mitigating it will require training of emergency staff in semiological diagnosis. Status epilepticus response protocols should incorporate appropriate diagnostic re-evaluations at each step of treatment escalation, especially in clinical trials.
MeSH term(s)	Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Anticonvulsants/therapeutic use ; Child ; Diagnostic Errors ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Seizures/diagnosis ; Seizures/drug therapy ; Status Epilepticus/diagnosis ; Status Epilepticus/drug therapy ; Young Adult
Chemical Substances	Anticonvulsants
Language	English
Publishing date	2021-08-06
Publishing country	England
Document type	Journal Article
ZDB-ID	3087-9
ISSN	1468-330X ; 0022-3050
ISSN (online)	1468-330X
ISSN	0022-3050
DOI	10.1136/jnnp-2021-326443
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Article ; Online: Linking gene expression patterns and brain morphometry to trauma and symptom severity in patients with functional seizures.

Jungilligens, Johannes / Popkirov, Stoyan / Perez, David L / Diez, Ibai

Psychiatry research. Neuroimaging

2022 Volume 326, Page(s) 111533

Abstract: Within stress-diathesis models, adverse life experiences (ALEs) increase the susceptibility to functional neurological symptoms through neuroplasticity effects. We aimed to characterize potential genetic influences on this relationship in 20 patients ... ...

Abstract	Within stress-diathesis models, adverse life experiences (ALEs) increase the susceptibility to functional neurological symptoms through neuroplasticity effects. We aimed to characterize potential genetic influences on this relationship in 20 patients with functional seizures. Questionnaires, structural MRIs and Allen Human Brain Atlas gene expression information were used to probe the intersection of symptom severity (Somatoform Dissociation Questionnaire, SDQ-20), ALE burden, and gray matter volumes. SDQ-20 scores positively correlated with sexual trauma, emotional neglect, and threat to life experiences. Higher SDQ-20 scores related to lower bilateral insula, left orbitofrontal, right amygdala, and perigenual/posterior cingulate volumes. Higher sexual trauma burden correlated with lower right posterior insula and putamen volumes; higher emotional neglect related to lower bilateral insula/right amygdala volumes. Findings in left insula/ventral precentral gyrus (SDQ-20), right insula/putamen (sexual trauma), and right amygdala (emotional neglect) held when controlling for comorbid psychopathology. At the intersection of symptom severity and sexual trauma volumetric findings, genes overrepresented in adrenergic, serotonergic, and oxytocin receptor signaling as well as in cortical and amygdala development were spatially correlated. In conclusion, ALEs and symptom severity were associated with gray matter volumes in cingulo-insular and amygdala areas, spatially overlapping with expression patterns of genes involved in stress-related signaling and neurodevelopment.
Language	English
Publishing date	2022-08-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	445361-x
ISSN	1872-7506 ; 1872-7123 ; 0925-4927 ; 0165-1781
ISSN (online)	1872-7506 ; 1872-7123
ISSN	0925-4927 ; 0165-1781
DOI	10.1016/j.pscychresns.2022.111533
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Article ; Online: The relationship of action, affect, and metacognition in functional seizures.

Jungilligens, Johannes / Flohr, Marie-Christin / Lange, Miriam / Wellmer, Jörg / Popkirov, Stoyan

Journal of clinical and experimental neuropsychology

2023 Volume 45, Issue 10, Page(s) 1003–1013

Abstract: Introduction: Metacognition provides a lens through which individuals experience, interpret, and respond to their affective states and behavior; it might thus influence complex neuropsychiatric conditions such as functional seizures - events ... ...

Abstract	Introduction: Metacognition provides a lens through which individuals experience, interpret, and respond to their affective states and behavior; it might thus influence complex neuropsychiatric conditions such as functional seizures - events characterized by states of heightened affective arousal and the disinhibition of prepotent behavior. In this pilot study, we aimed to establish a better understanding of the role of metacognition in functional seizures and its relationship to affective arousal and behavioral disinhibition (i.e., problems in suppressing prepared behavior). We hypothesized that affective arousal is related to higher behavioral disinhibition as well as slower reaction times, that affect and action (performing vs. not performing a movement) are related to memory and metacognition, and that metacognition is related to illness characteristics. Methods: We used a combination of an emotional go/no-go and a metacognitive recognition task with affectively valenced and neutral images in 18 patients with functional seizures. We compared markers of behavioral inhibition as well as indices for memory and metacognitive performance between affective (vs. neutral) and action/go (vs. inhibition/no-go) conditions. Results: Contrary to our hypothesis, behavioral disinhibition was not different between conditions. However, we found slower reaction times for affectively valenced stimuli. Memory performance and metacognition were better for affectively valenced pictures and for pictures used in go trials (i.e., associated with action/performing the movement). Illness factors (illness duration, seizure frequency, levels of self-reported anxiety) were correlated with aspects of metacognition. Conclusions: This pilot study offers first insights into alterations in metacognition related to action and affect in patients with functional seizures; specifically, that affectively valenced stimuli and active engagement are related to enhanced memory and metacognition. This relationship was also found with respect to illness factors. These results provide insight into potentially underlying pathomechanisms, although the lack of a control group limits evaluating the specificity of these findings.
MeSH term(s)	Humans ; Male ; Female ; Adult ; Seizures/physiopathology ; Seizures/psychology ; Metacognition/physiology ; Reaction Time/physiology ; Middle Aged ; Pilot Projects ; Inhibition, Psychological ; Affect/physiology ; Neuropsychological Tests ; Young Adult
Language	English
Publishing date	2023-11-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605982-x
ISSN	1744-411X ; 0168-8634 ; 1380-3395
ISSN (online)	1744-411X
ISSN	0168-8634 ; 1380-3395
DOI	10.1080/13803395.2023.2287778
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Article: Specific relations of visual skills and executive functions in elite soccer players.

Knöllner, Antonia / Memmert, Daniel / von Lehe, Marec / Jungilligens, Johannes / Scharfen, Hans-Erik

Frontiers in psychology

2022 Volume 13, Page(s) 960092

Abstract: Visual and cognitive skills are key to successful functioning in highly demanding settings such as elite sports. However, their mutual influence and interdependencies are not sufficiently understood yet. This cross-sectional study examined the ... ...

Abstract	Visual and cognitive skills are key to successful functioning in highly demanding settings such as elite sports. However, their mutual influence and interdependencies are not sufficiently understood yet. This cross-sectional study examined the relationship between visual skills and executive functions in elite soccer players. Fifty-nine male elite soccer players (age: 18-34 years) performed tests assessing visual clarity (left-, right-, and both eyes), contrast sensitivity, near-far quickness, and hand-eye coordination. Executive function measures included working memory capacity, cognitive flexibility, inhibition and selective attention. Overall, visual abilities were largely correlated with executive functions. Near-far quickness performance showed a large correlation with an executive function total score as well as with cognitive flexibility, working memory, and especially selective attention. Visual clarity and contrast sensitivity were moderately correlated with the cognition total score. Most consistent correlations with the visual functions were present for working memory. These findings present an overall vision-cognition relationship but also very specific linkages among subcategories of these functions, especially meaningful relations between near-far quickness, selective attention and cognitive flexibility. Further studies are needed to investigate the neuropsychological mechanisms accounting for the correlations and possible improvements of the executive functions by training specific visual skills.
Language	English
Publishing date	2022-08-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2563826-9
ISSN	1664-1078
ISSN	1664-1078
DOI	10.3389/fpsyg.2022.960092
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Article ; Online: A new science of emotion: implications for functional neurological disorder.

Jungilligens, Johannes / Paredes-Echeverri, Sara / Popkirov, Stoyan / Barrett, Lisa Feldman / Perez, David L

Brain : a journal of neurology

2022 Volume 145, Issue 8, Page(s) 2648–2663

Abstract: Functional neurological disorder reflects impairments in brain networks leading to distressing motor, sensory and/or cognitive symptoms that demonstrate positive clinical signs on examination incongruent with other conditions. A central issue in ... ...

Abstract	Functional neurological disorder reflects impairments in brain networks leading to distressing motor, sensory and/or cognitive symptoms that demonstrate positive clinical signs on examination incongruent with other conditions. A central issue in historical and contemporary formulations of functional neurological disorder has been the mechanistic and aetiological role of emotions. However, the debate has mostly omitted fundamental questions about the nature of emotions in the first place. In this perspective article, we first outline a set of relevant working principles of the brain (e.g. allostasis, predictive processing, interoception and affect), followed by a focused review of the theory of constructed emotion to introduce a new understanding of what emotions are. Building on this theoretical framework, we formulate how altered emotion category construction can be an integral component of the pathophysiology of functional neurological disorder and related functional somatic symptoms. In doing so, we address several themes for the functional neurological disorder field including: (i) how energy regulation and the process of emotion category construction relate to symptom generation, including revisiting alexithymia, 'panic attack without panic', dissociation, insecure attachment and the influential role of life experiences; (ii) re-interpret select neurobiological research findings in functional neurological disorder cohorts through the lens of the theory of constructed emotion to illustrate its potential mechanistic relevance; and (iii) discuss therapeutic implications. While we continue to support that functional neurological disorder is mechanistically and aetiologically heterogenous, consideration of how the theory of constructed emotion relates to the generation and maintenance of functional neurological and functional somatic symptoms offers an integrated viewpoint that cuts across neurology, psychiatry, psychology and cognitive-affective neuroscience.
MeSH term(s)	Affective Symptoms ; Brain ; Conversion Disorder ; Emotions ; Humans ; Medically Unexplained Symptoms
Language	English
Publishing date	2022-06-05
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awac204
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Article ; Online: Research on dissociative seizures: A bibliometric analysis and visualization of the scientific landscape.

Popkirov, Stoyan / Jungilligens, Johannes / Schlegel, Uwe / Wellmer, Jörg

Epilepsy & behavior : E&B

2018 Volume 83, Page(s) 162–167

Abstract: Dissociative seizures are a common and often elusive differential diagnosis in epilepsy centers. Considering their high prevalence, long diagnostic delays, and disappointing rates of treatment response, scientific research dedicated to dissociative ... ...

Abstract	Dissociative seizures are a common and often elusive differential diagnosis in epilepsy centers. Considering their high prevalence, long diagnostic delays, and disappointing rates of treatment response, scientific research dedicated to dissociative seizures is surprisingly scarce. In order to chart the scientific landscape of dissociative seizures and to visualize thematic clusters and trends in research, a comprehensive bibliometric analysis was performed. The Web of Science database was examined to identify relevant English language documents from the last half-century. A total of 1751 documents with titles referring to dissociative seizures were identified. Automated textual analysis of all titles and abstracts revealed that research clusters around three major topics: differential diagnosis in epilepsy centers, management and treatment, and psychopathology. Time analysis of term networks revealed that the focus of clinical research has moved from diagnostic procedures to treatment approaches. Furthermore, interest within etiological research is shifting from an emphasis on early life trauma and personality traits to the role of anxiety and emotion regulation. With respect to individual contributing authors, a relatively small network of prolific scientists with a remarkable degree of collaboration emerges. By mapping relevant publications, it becomes evident that dissociative seizures still represent a subject mostly within the realm of neurology and epileptology, with a tendency to settle in the latter domain. This analysis sheds light on an important niche subject and highlights trends in research focus and output.
MeSH term(s)	Bibliometrics ; Biomedical Research/methods ; Biomedical Research/trends ; Conversion Disorder/diagnosis ; Conversion Disorder/epidemiology ; Conversion Disorder/psychology ; Diagnosis, Differential ; Dissociative Disorders/diagnosis ; Dissociative Disorders/epidemiology ; Dissociative Disorders/psychology ; Emotions ; Epilepsy/diagnosis ; Epilepsy/epidemiology ; Epilepsy/psychology ; Humans ; Seizures/diagnosis ; Seizures/epidemiology ; Seizures/psychology
Language	English
Publishing date	2018-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2010587-3
ISSN	1525-5069 ; 1525-5050
ISSN (online)	1525-5069
ISSN	1525-5050
DOI	10.1016/j.yebeh.2018.03.041
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