Simultane Erfassung von Verhaltensdaten, evozierten Potentialen und funktioneller MRT bei einer Aufgabe zur Verhaltenskontrolle

Ziel der Arbeit war die Untersuchung exekutiver Funktionen, in diesem Fall der Inhibition und der Volition, also der freien Entscheidung mittels simultaner EEG- und fMRT-Datenerhebung. Mit dem EEG lassen sich Datensätze mit einer hohen zeitlichen Auflösung generieren. Als neurophysiologisches Korrelat auf einen Stimulus erhält man sog. Ereignis korrelierte Potentiale (EKPs), die nach einer bestimmten Zeitdauer nach Stimuluspräsentation auftreten. Die räumliche Auflösung dieser Methode ist jedoch stark limitiert. Andererseits erhält man mit der fMRT Datensätze mit einer hohen räumlichen, jedoch geringen zeitlichen Auflösung. Mittels einer neuen Methode, der sog. Single-Trial-Koppelung können Datensätze generiert werden, die beide Modalitäten miteinander vereinen. Somit können Rückschlüsse über die zeitliche Aktivierung von Hirnarealen gezogen werden.15 gesunde Probanden nahmen an einem adaptierten, auditiven Go/NoGo-Paradigma teil, welches um eine Volitionsbedingung erweitert wurde. Es wurden Töne mit unterschiedlich hoher Frequenz demonstriert. Bei der Go-Bedingung (mittelhoch-hoch) mussten die Probanden so schnell wie möglich eine Reaktionstaste betätigen. Bei der NoGo-Bedingung (mittelhoch-tief) musssten sie dies unterlassen und bei der Volitionsbedingung (2x mittelhoch) mussten sie sich entscheiden, ob sie die Reaktionstaste drücken wollten oder nicht. Die fMRT-Auswertung erfolte mit dem Programm Brain Voyager, die EEG-Daten wurden zunächst mit EEGlab vorverarbeitet und dann mit dem Programm Brain Vision Analyzer analysiert. Bei der Single-Trial-Analyse wurden die EEG-Daten jedes einzelnen Durchgangs mit den BOLD-Veränderungen im fMRT korreliert. Technisch wurden dabei bei der Berechnung des sog. Allgemeinen Linearen Modells die Signaländerungen im EEG für bestimmte Zeiträume berücksichtigt. Auf diese Weise kann man Hirnregionen darstellen, bei denen die in der fMRT gemessenen Signaländerungen am stärksten mit der Signaländerung im EEG korrelieren. Die Single-Trial-Analyse wurde für das N2-Potential bei Volition und NoGo an der Elektrode Fz durchgeführt, für die P300 bei NoGo an Cz und für Volition und Go an Pz.Bei der Auswertung der hämodynamischen Daten zeigten sich für die Bedingung Volition gegen eine Kontrollbedingung Aktivierungen im Bereich der prä-SMA und des dorsolateralen präfrontalen Kortex (DLPFC). Elektrophysiologisch zeigte sich ein negatives Potential nach ca. 200ms (N2) und ein positives Potential nach ca. 300ms (P300). In der Single-Trial-Analyse zeigte sich, dass das N2-Potential während der Volitionsbedingung vornehmlich mit medio-frontalen Hirnregionen wie der SMA und lateral-frontalen Arealen assoziiert war. Das P300-Potential bot ebenfalls Aktiveriungen in lateral-frontalen Arealen und in der temporoparietalen Übergangszone. Bei der Inhibition von Verhalten zeigten sich bei Analyse der fMRT-Daten Aktiveriungen im Bereich des Gyrus frontalis superior und des DLPFC. Das N2-Potential war hier vornehmlich mit frontalen Bereichen wie dem DLPFC und dem ventro-lateralen präfrontalen Kortex (VLPFC) assoziiert. Das NoGo-P300-Potential hingegen lieferte Minderaktivierungen in allen für Motorik wichtigen Bereiche.Durch die direkte Korrelation von hämodynamischen und elektrophysiologischen Daten ist es uns gelungen, nicht nur diejenigen Hirnareale darzustellen, die bei den einzelnen Versuchsbedingungen aktiviert waren, sondern auch zu zeigen, wie es sich mit der zeitlichen Organisation innerhalb dieses neuronalen Netzwerkes verhält. Darüber hinaus konnten wir zeigen, dass die EKPs je nach Versuchsbedingung von unterschiedlichen Hirngeneratoren erzeugt wurden, was den Schluss zulässt, dass die EKPs abhängig von den jeweiligen Versuchsbedingungen sind und somit auch stets eine andere Funktion repräsentieren. Zudem konnten wir bei der Single-Trial-Analyse eine Beteiligung jener Hirnareale zeigen, welche auch bei der isolierten Auswertung der hämodynamischen Daten identifiziert werden konnten, was den Schluss zulässt, dass die Signale, die in beiden Modalitäten erzeugt wurden, zu einem großen Teil von denselben neuronalen Generatoren in Abhängigkeit der Versuchsbedingung erzeugt wurden

Predictive Capability of an iPad-Based Medical Device (medx) for the Diagnosis of Vertigo and Dizziness

Background:Making the correct diagnosis of patients presenting with vertigo and dizziness in clinical practice is often challenging. Objective:In this study we analyzed the usage of the iPad based program medx in the prediction of different clinical vertigo and dizziness diagnoses . We examined the power of medx to distinguish between different vertigo diagnoses. Patients and methods:The data collection was done in the outpatient clinic of the German Center of Vertigo and Balance Disorders. The “gold standard diagnosis” was defined as the clinical diagnosis of the specialist during the visit of the patient standardized history and clinical examination. Another independent and blinded physician finalized each patient’s case in constellatory diagnostic of medx by entering all available clinical information in the system. The accuracy, sensitivity, specificity as well as positive and negative predictive values for the most common diagnoses were determined. Sixteen possible different vertigo and dizziness diagnoses could be provided by medx constellatory diagnostic system. These diagnoses were compared to the “gold standard” by retrospective review of the charts of the patients over the study period. Results:610 patients (mean age58.1±16.3 years, 51.2 female) were included. The accuracy for the most common diagnoses was between 82.1- 96.6 with a sensitivity from 40- 80.5 and a specificity of more than 80. When analyzing the quality of medx in a multiclass-problem for the six most common clinical diagnoses the sensitivity, specificity, positive and negative predictive value were as follows: Bilateral vestibulopathy (81.6, 97.1, 71.1, 97.5), Menière's disease (77.8, 97.6, 87., 95.3), benign paroxysmal positional vertigo (61.7, 98.3, 86.6, 93.4), downbeat nystagmus syndrome (69.6, 97.7, 71.1, 97.5), vestibular migraine (34.7, 97.8, 76.1, 88.3) and phobic postural vertigo (80.5, 82,5, 52.5, 94.6), Conclusions:This study demonstrates that medx is a new and easy approach to screen for different diagnoses. With the high specificity and high negative predictive value the system helps to rule out differential diagnoses and can therefore also lead to a cost reduction in health care system. However, the sensitivity was unexpectedly low, especially for vestibular migraine. All in all, this device can only be a complementary tool, in particular for non-experts in the field

Psychiatric comorbidity and psychosocial impairment among patients with vertigo and dizziness

Background: Vertigo and dizziness are often not fully explained by an organic illness, but instead are related to psychiatric disorders. This study aimed to evaluate psychiatric comorbidity and assess psychosocial impairment in a large sample of patients with a wide range of unselected organic and non-organic (ie, medically unexplained) vertigo/dizziness syndromes. Methods: This cross-sectional study involved a sample of 547 patients recruited from a specialised interdisciplinary treatment centre for vertigo/dizziness. Diagnostic evaluation included standardised neurological examinations, structured clinical interview for major mental disorders (SCID-I) and self-report questionnaires regarding dizziness, depression, anxiety, somatisation and quality of life. Results: Neurological diagnostic workup revealed organic and non-organic vertigo/dizziness in 80.8% and 19.2% of patients, respectively. In 48.8% of patients, SCID-I led to the diagnosis of a current psychiatric disorder, most frequently anxiety/phobic, somatoform and affective disorders. In the organic vertigo/dizziness group, 42.5% of patients, particularly those with vestibular paroxysmia or vestibular migraine, had a current psychiatric comorbidity. Patients with psychiatric comorbidity reported more vertigo-related handicaps, more depressive, anxiety and somatisation symptoms, and lower psychological quality of life compared with patients without psychiatric comorbidity. Conclusions: Almost half of patients with vertigo/dizziness suffer from a psychiatric comorbidity. These patients show more severe psychosocial impairment compared with patients without psychiatric disorders. The worst combination, in terms of vertigo-related handicaps, is having non-organic vertigo/dizziness and psychiatric comorbidity. This phenomenon should be considered when diagnosing and treating vertigo/dizziness in the early stages of the disease

Cortical alterations in phobic postural vertigo - a multimodal imaging approach

Objective: Functional dizziness syndromes are among the most common diagnoses made in patients with chronic dizziness, but their underlying neural characteristics are largely unknown. The aim of this neuroimaging study was to analyze the disease-specific brain changes in patients with phobic postural vertigo (PPV). Methods: We measured brain morphology, task response, and functional connectivity in 44 patients with PPV and 44 healthy controls. Results: The analyses revealed a relative structural increase in regions of the prefrontal cortex and the associated thalamic projection zones as well as in the primary motor cortex. Morphological increases in the ventrolateral prefrontal cortex positively correlated with disease duration, whereas increases in dorsolateral, medial, and ventromedial prefrontal areas positively correlated with the Beck depression index. Visual motion stimulation caused an increased task-dependent activity in the subgenual anterior cingulum and a significantly longer duration of the motion aftereffect in the patients. Task-based functional connectivity analyses revealed aberrant involvement of interoceptive, fear generalization, and orbitofrontal networks. InterpretationOur findings agree with some of the typical characteristics of functional dizziness syndromes, for example, excessive self-awareness, anxious appraisal, and obsessive controlling of posture. This first evidence indicates that the disease-specific mechanisms underlying PPV are related to networks involved in mood regulation, fear generalization, interoception, and cognitive control. They do not seem to be the result of aberrant processing in cortical visual, visual motion, or vestibular regions

Predictive Capability of an iPad-Based Medical Device (medx) for the Diagnosis of Vertigo and Dizziness

BackgroundMaking the correct diagnosis of patients presenting with vertigo and dizziness in clinical practice is often challenging.ObjectiveIn this study we examined the performance of the iPad based program medx in the prediction of different clinical vertigo and dizziness diagnoses and as a diagnostic tool to distinguish between them.Patients and methodsThe data collection was done in the outpatient clinic of the German Center of Vertigo and Balance Disorders. The “gold standard diagnosis” was defined as the clinical diagnosis of the specialist during the visit of the patient based on standardized history and clinical examination. Another independent and blinded physician finalized each patient’s case in the constellatory diagnostic system of medx based on an algorithm using all available clinical information. These diagnoses were compared to the “gold standard” by retrospective review of the charts of the patients. The accuracy provided by medx was defined as the number of correctly classified diagnoses. In addition, the probability of being test positive when a disease was present (sensitivity), of being test negative when a disease was absent (specificity), of having the disease when the test is positive (positive predictive value) and of not having the disease when the test is negative (negative predictive value) for the most common diagnoses were reported. Sixteen possible different vertigo and dizziness diagnoses could be provided by medx.ResultsA total of 610 patients (mean age 58.1 ± 16.3 years, 51.2% female) were included. The accuracy for the most common diagnoses was between 82.1 and 96.6% with a sensitivity of 40 to 80.5% and a specificity of more than 80%. When analyzing the quality of medx in a multiclass problem for the six most common clinical diagnoses, the sensitivity, specificity, positive and negative predictive values were as follows: Bilateral vestibulopathy (81.6, 97.1, 71.1, and 97.5%), Menière’s disease (77.8, 97.6, 87.0, and 95.3%), benign paroxysmal positional vertigo (61.7, 98.3, 86.6, and 93.4%), downbeat nystagmus syndrome (69.6, 97.7, 71.1, and 97.5%), vestibular migraine (34.7, 97.8, 76.1, and 88.3%), and phobic postural vertigo (80.5, 82.5, 52.5, and 94.6%).ConclusionThis study demonstrates that medx is a new and easy approach to screen for different diagnoses. With the high specificity and negative predictive value, the system helps to rule out differential diagnoses and can therefore also lead to a cost reduction in the health care system. However, the sensitivity was unexpectedly low, especially for vestibular migraine. All in all, this device can only be a complementary tool, in particular for non-experts in the field