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In neurodegenerative diseases, the characterization of the prodromal phase is essential for the future application of disease-modifying therapies. X-linked dystonia-parkinsonism is a hereditary neurodegenerative movement disorder characterized by severe adult-onset dystonia accompanied by parkinsonism. Distinct striatal and pallidal atrophy is present already in early disease stages indicating a long-lasting presymptomatic degenerative process. To gain insight into the prodromal phase of X-linked dystonia-parkinsonism, structural and iron-sensitive magnetic resonance imaging (MRI) was performed in 10 non-manifesting carriers and 24 healthy controls in a double-blind fashion. Seventeen patients with X-linked dystonia-parkinsonism were recruited to replicate previous findings of basal ganglia pathology and iron accumulation. Age at onset was estimated in non-manifesting carriers and patients using the repeat length of the hexanucleotide expansion and 3 single-nucleotide polymorphisms associated with age at onset. Voxel-based morphometry and subcortical volumetry showed striatal and pallidal atrophy in non-manifesting carriers (~10%) and patients (~40%). Substantia nigra volume was similarly reduced in patients (~40%). Caudate volume correlated with time to estimated onset in non-manifesting carriers. Susceptibility-weighted imaging confirmed iron deposition in the anteromedial putamen in patients. Non-manifesting carriers also showed small clusters of iron accumulation in the same area after lowering the statistical threshold. In conclusion, basal ganglia atrophy and iron accumulation precede the clinical onset of X-linked dystonia-parkinsonism and can be detected years before the estimated disease manifestation. It thereby highlights the potential of multimodal imaging to identify clinically unaffected mutation carriers with incipient neurodegeneration and to monitor disease progression independent of clinical measures. Longitudinal studies are needed to further elucidate the onset and progression rate of neurodegeneration in prodromal X-linked dystonia-parkinsonism. ANN NEUROL 2023;93:999-1011.
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Trastornos Distónicos , Enfermedades Neurodegenerativas , Adulto , Humanos , Trastornos Distónicos/diagnóstico por imagen , Trastornos Distónicos/genética , Trastornos Distónicos/complicaciones , Ganglios Basales/diagnóstico por imagen , Ganglios Basales/patología , Imagen por Resonancia Magnética , Enfermedades Neurodegenerativas/patología , Atrofia/patología , HierroRESUMEN
PURPOSE: As measures of association between an adverse drug reaction (ADR) and exposure to a drug the reporting odds ratio (ROR) and the information component (IC) can be used. We sought to test the reliability of signal detection with these. METHODS: We simulated ADR counts as binomially distributed random numbers for different expected ADR frequencies and theoretical reporting odds ratios (RORs). We then calculated the empirical IC and the empirical ROR and their confidence intervals. The rate of signals that was detected despite a theoretical ROR of 1 represented the false positive rate, and represented the sensitivity if the ROR was >1. RESULTS: For expected case counts below 1 the false positive rate oscillates from 0.01 to 0.1 even though 0.025 were intended. Even beyond expected case counts of 5 oscillations can cover a range of 0.018 to 0.035. The first n oscillations with the largest amplitude are eliminated if a minimum case count of n is required. To detect an ROR of 2 with a sensitivity of 0.8, a minimum of 12 expected ADRs are required. In contrast, 2 expected ADRs suffice to detect an ROR of 4. CONCLUSION: Summaries of measures for disproportionality should include the expected number of cases in the group of interest if a signal was detected. If no signal was detected the sensitivity for the detection of a representative ROR or the minimum ROR that could be detected with probability 0.8 should be reported.
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Sistemas de Registro de Reacción Adversa a Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Oportunidad Relativa , Reproducibilidad de los Resultados , Bases de Datos Factuales , FarmacovigilanciaRESUMEN
A guideline is proposed that comprises the minimum items to be reported in research studies involving an eye tracker and human or non-human primate participant(s). This guideline was developed over a 3-year period using a consensus-based process via an open invitation to the international eye tracking community. This guideline will be reviewed at maximum intervals of 4 years.
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BACKGROUND: Early diagnosis in patients with neurodegenerative disorders is crucial to initiate disease-modifying therapies at a time point where progressive neurodegeneration can still be modified. OBJECTIVES: The objective of this study was to determine whether motor or non-motor signs of the disease occur as indicators of a prodromal phase of X-linked dystonia-parkinsonism (XDP), a highly-penetrant monogenic movement disorder with striking basal ganglia pathology. METHODS: In addition to a comprehensive clinical assessment, sensor-based balance and gait analyses were performed in non-manifesting mutation carriers (NMCs), healthy controls (HCs), and patients with XDP. Gradient-boosted trees (GBT) methodology was utilized to classify groups of interest. RESULTS: There were no clinically overt disease manifestations in the NMCs. Balance analysis, however, revealed a classification accuracy of 90% for the comparison of NMC versus HC. For the gait analysis, the best-performing GBT-based model showed a balanced accuracy of 95% (NMC vs. HC; walking at maximum speed). Using a separate analysis of genetic modifiers, several gait parameters correlated strongly with the estimated age at disease onset in the NMC group. CONCLUSIONS: Our study unraveled balance and gait abnormalities in NMCs that preceded the onset of XDP. These findings demonstrate prodromal motor changes among NMCs who will develop XDP with a very high likelihood in the future. Gait abnormalities had a predictive value for the estimated age at onset highlighting the impact of genetic modifiers in personalized treatment in monogenic neurodegenerative disorders. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Trastornos Distónicos , Enfermedades Genéticas Ligadas al Cromosoma X , Ganglios Basales/patología , Trastornos Distónicos/genética , Trastornos Distónicos/patología , Enfermedades Genéticas Ligadas al Cromosoma X/complicaciones , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , FenotipoRESUMEN
BACKGROUND: Hemispatial neglect results from unilateral brain damage and represents a disabling unawareness for objects in the hemispace opposite the brain lesion (contralesional). The patients' attentional bias for ipsilesional hemispace represents a hallmark of neglect, which results from an imbalanced attentional priority map in the brain. The aim of this study was to investigate whether gaze-contingent display (GCD) technology, reducing the visual salience of objects in ipsilesional hemispace, is able to rebalance this map and increase awareness and exploration of objects in the neglected contralesional hemispace. METHODS: Using remote eye-tracking, we recorded gaze positions in 19 patients with left hemispatial neglect following right-hemisphere stroke and 22 healthy control subjects, while they were watching static naturalistic scenes. There were two task conditions, free viewing (FV) or goal-directed visual search (VS), and four modification conditions including the unmodified original picture, a purely static modification and two differently strong modifications with an additional gaze-contingent mask (GC-LOW, GC-HIGH), that continuously reduced color saturation and contrast of objects in the right hemispace. RESULTS: The patients' median gaze position (Center of Fixation) in the original pictures was markedly deviated to the right in both tasks (FV: 6.8° ± 0.8; VS: 5.5° ± 0.7), reflecting the neglect-typical ipsilesional attention bias. GC modification significantly reduced this bias in FV (GC-HIGH: d = - 3.2 ± 0.4°; p < 0.001). Furthermore, in FV and VS, GC modification increased the likelihood to start visual exploration in the (neglected) left hemifield by about 20%. This alleviation of the ipsilesional fixation bias was not associated with an improvement in detecting left-side targets, in contrast, the GC mask even decreased and slowed the detection of right-side targets. Subjectively, patients found the intervention pleasant and most of the patients did not notice any modification. CONCLUSIONS: GCD technology can be used to positively influence visual exploration patterns in patients with hemispatial neglect. Despite an alleviation of the neglect-related ipsilesional fixation bias, a concomitant functional benefit (improved detection of contralesional targets) was not achieved. Future studies may investigate individualized GCD-based modifications as augmented reality applications during the activities of daily living.
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Sesgo Atencional , Trastornos de la Percepción , Accidente Cerebrovascular , Humanos , Actividades Cotidianas , Lateralidad Funcional , Trastornos de la Percepción/diagnóstico , Accidente Cerebrovascular/complicaciones , TecnologíaRESUMEN
BACKGROUND AND PURPOSE: The bedside head impulse test (bHIT) is used to differentiate vestibular neuritis (VN) from posterior circulation stroke (PCS) in patients presenting with acute vestibular syndrome (AVS). If assessed by neuro-otological experts, diagnostic accuracy is high. We report on its diagnostic accuracy when applied by nonexperts during routine clinical practice in the emergency department (ED), its impact on patient management, and the potential diagnostic yield of the video-oculography-supported head impulse test (vHIT). METHODS: Medical chart review of 38 AVS patients presenting to our university medical center's ED, assessed by neurology residents. We collected bHIT results (abnormal/peripheral or normal/central) and whether patients were admitted to the stroke unit or general neurological ward. Final diagnosis (VN, n = 24; PCS, n = 14) was determined by clinical course, magnetic resonance imaging, and vHIT. RESULTS: The bHIT's accuracy was only 58%. Its sensitivity for VN was high (88%), but due to many false-abnormal bHITs in PCS (36%), the specificity was low (64%). The vHIT yielded excellent specificity (100%) and moderate sensitivity (67%). The decision on the patient's further care was almost arbitrary and independent from the bHIT: 58% of VN and 57% of PCS patients were admitted to the stroke unit. CONCLUSIONS: The bHIT, applied by nonexperts during routine practice in the ED, has low accuracy, is too often mistaken as abnormal/peripheral, and is not consistently used for patients' in-hospital triage. As false-abnormal bHITs can lead to misdiagnosis/mistreatment of stroke patients, we recommend that bHIT applied by nonexperts should be reassessed by a neuro-otological expert or preferably quantitative vHIT in the ED.
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Accidente Cerebrovascular , Neuronitis Vestibular , Servicio de Urgencia en Hospital , Prueba de Impulso Cefálico , Humanos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico , Vértigo/diagnóstico , Vértigo/etiología , Neuronitis Vestibular/diagnósticoRESUMEN
Borderline Personality Disorder (BPD) is characterized by an increased emotional sensitivity and dysfunctional capacity to regulate emotions. While amygdala and prefrontal cortex interactions are regarded as the critical neural mechanisms underlying these problems, the empirical evidence hereof is inconsistent. In the current study, we aimed to systematically test different properties of brain connectivity and evaluate the predictive power to detect borderline personality disorder. Patients with borderline personality disorder (n = 51), cluster C personality disorder (n = 26) and non-patient controls (n = 44), performed an fMRI emotion regulation task. Brain network analyses focused on two properties of task-related connectivity: phasic refers to task-event dependent changes in connectivity, while tonic was defined as task-stable background connectivity. Three different network measures were estimated (strength, local efficiency, and participation coefficient) and entered as separate models in a nested cross-validated linear support vector machine classification analysis. Borderline personality disorder vs. non-patient controls classification showed a balanced accuracy of 55%, which was not significant under a permutation null-model, p = 0.23. Exploratory analyses did indicate that the tonic strength model was the highest performing model (balanced accuracy 62%), and the amygdala was one of the most important features. Despite being one of the largest data-sets in the field of BPD fMRI research, the sample size may have been limited for this type of classification analysis. The results and analytic procedures do provide starting points for future research, focusing on network measures of tonic connectivity, and potentially focusing on subgroups of BPD.
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Trastorno de Personalidad Limítrofe , Encéfalo , Regulación Emocional , Trastorno de Personalidad Limítrofe/clasificación , Trastorno de Personalidad Limítrofe/diagnóstico por imagen , Trastorno de Personalidad Limítrofe/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Estudios de Casos y Controles , Regulación Emocional/fisiología , Humanos , Imagen por Resonancia MagnéticaRESUMEN
We examined the effect of galvanic vestibular stimulation (GVS) on resting state brain activity using fMRI (rs-fMRI) in patients with bilateral vestibulopathy. Based on our previous findings, we hypothesized that GVS, which excites the vestibular nerve fibers, (a) increases functional connectivity in temporoparietal regions processing vestibular signals, and (b) alleviates abnormal visual-vestibular interaction. Rs-fMRI of 26 patients and 26 age-matched healthy control subjects was compared before and after GVS. The stimulation elicited a motion percept in all participants. Using different analyses (degree centrality, DC; fractional amplitude of low frequency fluctuations [fALFF] and seed-based functional connectivity, FC), group comparisons revealed smaller rs-fMRI in the right Rolandic operculum of patients. After GVS, rs-fMRI increased in the right Rolandic operculum in both groups and in the patients' cerebellar Crus 1 which was related to vestibular hypofunction. GVS elicited a fALFF increase in the visual cortex of patients that was inversely correlated with the patients' rating of perceived dizziness. After GVS, FC between parietoinsular cortex and higher visual areas increased in healthy controls but not in patients. In conclusion, short-term GVS is able to modulate rs-fMRI in healthy controls and BV patients. GVS elicits an increase of the reduced rs-fMRI in the patients' right Rolandic operculum, which may be an important contribution to restore the disturbed visual-vestibular interaction. The GVS-induced changes in the cerebellum and the visual cortex were associated with lower dizziness-related handicaps in patients, possibly reflecting beneficial neural plasticity that might subserve visual-vestibular compensation of deficient self-motion perception.
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Vestibulopatía Bilateral/fisiopatología , Cerebelo/fisiopatología , Corteza Cerebral/fisiopatología , Conectoma/métodos , Mareo/fisiopatología , Cinestesia/fisiología , Red Nerviosa/fisiopatología , Plasticidad Neuronal/fisiología , Anciano , Vestibulopatía Bilateral/complicaciones , Vestibulopatía Bilateral/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Mareo/diagnóstico por imagen , Mareo/etiología , Estimulación Eléctrica , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagenRESUMEN
OBJECTIVES: Smooth pursuit eye movement deficits are an established psychosis biomarker across schizophrenia, schizoaffective and psychotic bipolar disorder (BPwP). Whether smooth pursuit deficits are also seen in bipolar disorder without psychosis (BPwoP) is unclear. Here we present data from the Psychosis and Affective Research Domains and Intermediate Phenotypes (PARDIP) study comparing bipolar patients with and without psychotic features. METHODS: Probands with BPwP (N = 49) and BPwoP (N = 36), and healthy controls (HC, N = 71) performed eye tracking tasks designed to evaluate specific sensorimotor components relevant for pursuit initiation and pursuit maintenance. RESULTS: While BPwoP did not differ from either BPwP or HC on initial eye acceleration, they performed significantly better than BPwP on early (P < .01) and predictive (P = .02) pursuit maintenance measures, both without differing from HC. BPwP were impaired compared to HC on initial eye acceleration, and on early and predictive pursuit maintenance (all P < .01). In contrast to the three pursuit measures, BPwP and BPwoP were both impaired on general neurocognitive assessments in relation to HC (both P < .001), without a significant difference between the two bipolar patient groups. CONCLUSIONS: Our findings support the model that impairments of sensorimotor and cognitive processing as required for early and later predictive smooth pursuit maintenance are relatively specific to those bipolar patients with a history of psychosis. This suggests that the neural circuitry for developing feed-forward predictive models for accurate pursuit maintenance is associated with the occurrence of psychotic features in bipolar patients. In contrast, generalized neuropsychological impairments did not differentiate the two bipolar patient groups.
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Trastorno Bipolar/fisiopatología , Trastorno Bipolar/psicología , Trastornos Psicóticos/fisiopatología , Seguimiento Ocular Uniforme/fisiología , Adulto , Biomarcadores , Trastorno Bipolar/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , EsquizofreniaRESUMEN
BACKGROUND: Eye tracking dysfunction (ETD) observed with standard pursuit stimuli represents a well-established biomarker for schizophrenia. How ETD may manifest during free visual exploration of real-life movies is unclear. METHODS: Eye movements were recorded (EyeLink®1000) while 26 schizophrenia patients and 25 healthy age-matched controls freely explored nine uncut movies and nine pictures of real-life situations for 20 s each. Subsequently, participants were shown still shots of these scenes to decide whether they had explored them as movies or pictures. Participants were additionally assessed on standard eye-tracking tasks. RESULTS: Patients made smaller saccades (movies (p = 0.003), pictures (p = 0.002)) and had a stronger central bias (movies and pictures (p < 0.001)) than controls. In movies, patients' exploration behavior was less driven by image-defined, bottom-up stimulus saliency than controls (p < 0.05). Proportions of pursuit tracking on movies differed between groups depending on the individual movie (group*movie p = 0.011, movie p < 0.001). Eye velocity on standard pursuit stimuli was reduced in patients (p = 0.029) but did not correlate with pursuit behavior on movies. Additionally, patients obtained lower rates of correctly identified still shots as movies or pictures (p = 0.046). CONCLUSION: Our results suggest a restricted centrally focused visual exploration behavior in patients not only on pictures, but also on movies of real-life scenes. While ETD observed in the laboratory cannot be directly transferred to natural viewing conditions, these alterations support a model of impairments in motion information processing in patients resulting in a reduced ability to perceive moving objects and less saliency driven exploration behavior presumably contributing to alterations in the perception of the natural environment.
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Conducta Exploratoria/fisiología , Percepción de Movimiento/fisiología , Reconocimiento Visual de Modelos/fisiología , Seguimiento Ocular Uniforme/fisiología , Esquizofrenia/fisiopatología , Adulto , Medidas del Movimiento Ocular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Películas CinematográficasRESUMEN
BACKGROUND: Borderline personality disorder (BPD) is characterized by emotion dysregulation; however, it is unclear whether this is restricted to negative emotional stimuli or to what degree this is specific to BPD. We investigated neural correlates of hypothesized increased emotional sensitivity and impaired emotion regulation in patients with BPD. METHODS: During functional MRI (fMRI) scanning, patients with BPD, nonpatient controls and patients with cluster-C personality disorder completed an emotion regulation task, including negative, positive and erotic social pictures. RESULTS: We included 55 patients with BPD, 42 nonpatient controls and 24 patients with cluster-C personality disorder in our analyses. Passive viewing of negative stimuli resulted in greater activity in the anterior insula, temporoparietal junction and dorsolateral prefrontal cortex in patients with BPD than in nonpatient controls. The increased activity in the anterior insula and temporoparietal junction was also present when patients with BPD viewed positive stimuli. During regulation of negative stimuli compared with passive viewing, nonpatient controls showed greater activity in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, middle temporal gyrus and bilateral inferior parietal lobule. Patients with BPD did not show this increase in activity. LIMITATIONS: Findings cannot be generalized to men, and patients represented a heterogeneous group regarding comorbid diagnoses and medication. CONCLUSION: When looking at emotional stimuli, patients with BPD showed a unique pattern of activity, suggesting an increase in brain activity involved in emotion generation. In the case of negative stimuli this is accompanied by increased activity in regulation areas. In contrast, increase of regulation processes seems absent when patients with BPD are explicitly instructed to regulate. Results of diagnosis specificity support a dimensional rather than a dichotomous differentiation between BPD and cluster-C personality disorder regarding emotional sensitivity and emotional regulation of social stimuli.
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Trastorno de Personalidad Limítrofe/fisiopatología , Encéfalo/fisiopatología , Emociones/fisiología , Trastornos de la Personalidad/fisiopatología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Estimulación Luminosa , Adulto JovenRESUMEN
BACKGROUND: Borderline personality disorder (BPD) is characterized by emotion dysregulation; however, it is unclear whether this is restricted to negative emotional stimuli or to what degree this is specific to BPD. We investigated neural correlates of hypothesized increased emotional sensitivity and impaired emotion regulation in patients with BPD. METHODS: During fMRI scanning, patients with BPD, nonpatient controls and patients with cluster-C personality disorder completed an emotion regulation task, including negative, positive and erotic social pictures. RESULTS: We included 55 patients with BPD, 42 nonpatient controls and 24 patients with cluster-C personality disorder in our analyses. Passive viewing of negative stimuli resulted in greater activity in the anterior insula, temporoparietal junction and dorsolateral prefrontal cortex in patients with BPD than in nonpatient controls. The increased activity in the anterior insula and temporoparietal junction was also present when patients with BPD viewed positive stimuli. During regulation of negative stimuli compared with passive viewing, nonpatient controls showed greater activity in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, middle temporal gyrus and bilateral inferior parietal lobule. Patients with BPD did not show this increase in activity. LIMITATIONS: Findings cannot be generalized to men, and patients represented a heterogeneous group regarding comorbid diagnoses and medication. CONCLUSION: When looking at emotional stimuli, patients with BPD showed a unique pattern of activity, suggesting an increase in brain activity involved in emotion generation. In the case of negative stimuli this is accompanied by increased activity in regulation areas. In contrast, increase of regulation processes seems absent when patients with BPD are explicitly instructed to regulate. Results of diagnosis specificity support a dimensional rather than a dichotomous differentiation between BPD and cluster-C personality disorder regarding emotional sensitivity and emotional regulation of social stimuli.
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Despite many reports on visual processing deficits in psychotic disorders, studies are needed on the integration of visual and non-visual components of eye movement control to improve the understanding of sensorimotor information processing in these disorders. Non-visual inputs to eye movement control include prediction of future target velocity from extrapolation of past visual target movement and anticipation of future target movements. It is unclear whether non-visual input is impaired in patients with schizophrenia. We recorded smooth pursuit eye movements in 21 patients with schizophrenia spectrum disorder, 22 patients with bipolar disorder, and 24 controls. In a foveo-fugal ramp task, the target was either continuously visible or was blanked during movement. We determined peak gain (measuring overall performance), initial eye acceleration (measuring visually driven pursuit), deceleration after target extinction (measuring prediction), eye velocity drifts before onset of target visibility (measuring anticipation), and residual gain during blanking intervals (measuring anticipation and prediction). In both patient groups, initial eye acceleration was decreased and the ability to adjust eye acceleration to increasing target acceleration was impaired. In contrast, neither deceleration nor eye drift velocity was reduced in patients, implying unimpaired non-visual contributions to pursuit drive. Disturbances of eye movement control in psychotic disorders appear to be a consequence of deficits in sensorimotor transformation rather than a pure failure in adding cognitive contributions to pursuit drive in higher-order cortical circuits. More generally, this deficit might reflect a fundamental imbalance between processing external input and acting according to internal preferences.
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Trastorno Bipolar/fisiopatología , Percepción de Movimiento/fisiología , Seguimiento Ocular Uniforme/fisiología , Esquizofrenia/fisiopatología , Adolescente , Adulto , Análisis de Varianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Escalas de Valoración Psiquiátrica , Tiempo de Reacción/fisiología , Adulto JovenRESUMEN
Emotion instability in borderline personality disorder (BPD) has been associated with an impaired fronto-limbic inhibitory network. However, functional connectivity (FC) underlying altered emotion regulation in BPD has yet to be established. Here, we used resting-state fMRI to investigate enduring effects of effortful emotion regulation on the amygdala intrinsic FC in BPD. In this multicenter study, resting-state fMRI was acquired before and after an emotion regulation task in 48 BPD patients and 39 non-patient comparison individuals. The bilateral amygdalae were used as a seed in the whole-brain FC analysis and two-way mixed ANOVA to test whether BPD patients exhibited weaker post-task increase in the amygdala intrinsic FC with the prefrontal cortex (PFC), compared to non-patients. Subsequently, we explored whether the results are common for personality disorders characterized by emotional problems, using additional data of 21 cluster-C personality disorder patients. In contrast to non-patients, BPD patients failed to show increased post-task amygdala resting-state FC with the medial, dorsolateral, ventrolateral PFC, and superior temporal gyrus, but surprisingly exhibited decreased FC with the posterior cingulate cortex and increased FC with the superior parietal lobule. In BPD patients, the emotion regulation task failed to increase resting-state amygdala FC with brain regions essential for effortful emotion regulation, which suggests: (a) altered cognitive control typically used to indirectly alleviate distress by reinterpreting the meaning of emotional stimuli; (b) impaired direct regulation of emotional responses, which might be common for personality disorders;
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Amígdala del Cerebelo/fisiopatología , Trastorno de Personalidad Limítrofe/fisiopatología , Conectoma/métodos , Emociones/fisiología , Corteza Prefrontal/fisiopatología , Autocontrol , Adulto , Amígdala del Cerebelo/diagnóstico por imagen , Trastorno de Personalidad Limítrofe/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Corteza Prefrontal/diagnóstico por imagen , Adulto JovenRESUMEN
Bilateral vestibular failure (BVF) is a severe chronic disorder of the labyrinth or the eighth cranial nerve characterized by unsteadiness of gait and disabling oscillopsia during head movements. According to animal data, vestibular input to the hippocampus is proposed to contribute to spatial memory and spatial navigation. Except for one seminal study showing the association of impaired spatial navigation and hippocampal atrophy, patient data in BVF are lacking. Therefore, we performed a voxel-wise comparison of the hippocampal gray matter volume (GMV) in a clinically representative sample of 27 patients with incomplete BVF and 29 age- and gender-matched healthy controls to test the hypothesis of hippocampal atrophy in BVF. Although the two groups did not generally differ in their hippocampal GMV, a reduction of GMV in the bilateral hippocampal CA3 region was significantly correlated with increased vestibulopathy-related clinical impairment. We propose that GMV reduction in the hippocampus of BVF patients is related to the severity of vestibular-induced disability which is in line with combined hippocampal atrophy and disorders of spatial navigation in complete vestibular deafferentation due to bilateral nerve section. Clinically, however, the most frequent etiologies of BVF cause incomplete lesions. Accordingly, hippocampus atrophy and deficits in spatial navigation occur possibly less frequently than previously suspected. Hum Brain Mapp 37:1998-2006, 2016. © 2016 Wiley Periodicals, Inc.
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Vestibulopatía Bilateral/patología , Sustancia Gris/patología , Hipocampo/patología , Anciano , Atrofia/patología , Vestibulopatía Bilateral/diagnóstico por imagen , Vestibulopatía Bilateral/fisiopatología , Estudios de Casos y Controles , Electroencefalografía , Potenciales Evocados/fisiología , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Reflejo Vestibuloocular/fisiología , Análisis de Regresión , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Patients with acute ischemic strokes frequently take an acetylsalicylic acid (ASA) premedication. We determined the impact of ASA on different thrombolysis strategies in vitro. METHODS: For two clot types made from platelet-rich plasma (one with and one without ASA) lysis rates were measured by weight loss after 1 h for five different groups: in control group A clots were solely placed in plasma; in groups B and C clots were treated with rt-PA (60 kU/ml), and in groups D and E clots were treated with desmoteplase (DSPA; 2 µg/ml). Ultrasound (2 MHz, 0.179 W/cm2) was included in groups C and E. The fibrin mesh structures of the clots were investigated by electron microscopy. RESULTS: For both clot types lysis rates increased significantly for all treatment strategies compared to their control group (each p < 0.001). The addition of ASA significantly increased the lysis rate in all 5 groups (each p < 0.001) and led to a ceiling effect concerning the treatment. A semiquantitative analysis of transmission electron micrographs revealed a decreased fibrin density for clots with ASA. For both clot types DSPA and ultrasound led to a significant dissolution of the fibrin mesh (both p = 0.029). CONCLUSIONS: In vitro ASA pretreatment leads to significantly increased lysis rates due to a weaker fibrin mesh in platelet-rich plasma clots.
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Aspirina/farmacología , Fibrina/metabolismo , Fibrinólisis/efectos de los fármacos , Fibrinolíticos/farmacología , Activadores Plasminogénicos/farmacología , Terapia Trombolítica/métodos , Terapia por Ultrasonido , Fibrina/ultraestructura , Humanos , CinéticaRESUMEN
Sleep deprivation impairs inhibitory control over reflexive behavior, and this impairment is commonly assumed to dissipate after recovery sleep. Contrary to this belief, here we show that fast reflexive behaviors, when practiced during sleep deprivation, is consolidated across recovery sleep and, thereby, becomes preserved. As a model for the study of sleep effects on prefrontal cortex-mediated inhibitory control in humans, we examined reflexive saccadic eye movements (express saccades), as well as speeded 2-choice finger motor responses. Different groups of subjects were trained on a standard prosaccade gap paradigm before periods of nocturnal sleep and sleep deprivation. Saccade performance was retested in the next morning and again 24 h later. The rate of express saccades was not affected by sleep after training, but slightly increased after sleep deprivation. Surprisingly, this increase augmented even further after recovery sleep and was still present 4 weeks later. Additional experiments revealed that the short testing after sleep deprivation was sufficient to increase express saccades across recovery sleep. An increase in speeded responses across recovery sleep was likewise found for finger motor responses. Our findings indicate that recovery sleep can consolidate motor disinhibition for behaviors practiced during prior sleep deprivation, thereby persistently enhancing response automatization.
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Desempeño Psicomotor/fisiología , Reflejo/fisiología , Privación de Sueño/fisiopatología , Adulto , Conducta de Elección , Electrooculografía , Femenino , Humanos , Masculino , Tiempo de Reacción/fisiología , Movimientos Sacádicos/fisiología , Adulto JovenRESUMEN
Social context plays an important role in human communication. Depending on the nature of the source, the same communication signal might be processed in fundamentally different ways. However, the selective modulation (or "gating") of the flow of neural information during communication is not fully understood. Here, we use multivoxel pattern analysis (MVPA) and multivoxel connectivity analysis (MVCA), a novel technique that allows to analyse context-dependent changes of the strength interregional coupling between ensembles of voxels, to examine how the human brain differentially gates content-specific sensory information during ongoing perception of communication signals. In a simulated electronic communication experiment, participants received two alternative text messages during fMRI ("happy" or "sad") which they believed had been sent either by their real-life friend outside the scanner or by a computer. A region in the dorsal medial prefrontal cortex (dmPFC) selectively increased its functional coupling with sensory-content encoding regions in the visual cortex when a text message was perceived as being sent by the participant's friend, and decreased its functional coupling with these regions when a text message was perceived as being sent by the computer. Furthermore, the strength of neural encoding of content-specific information of text messages in the dmPFC was modulated by the social tie between the participant and her friend: the more of her spare time a participant reported to spend with her friend the stronger was the neural encoding. This suggests that the human brain selectively gates sensory information into the relevant network for processing the mental states of others, depending on the source of the communication signal.
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Comunicación , Filtrado Sensorial/fisiología , Conducta Social , Medio Social , Adulto , Emociones , Expresión Facial , Femenino , Amigos/psicología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Red Nerviosa/fisiología , Corteza Prefrontal/fisiología , Corteza Visual/fisiología , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Right hemisphere stroke patients frequently experience spatial neglect, a severe lack of awareness for contralesional hemispace. Although neglect counts among the strongest predictors for poor functional outcome after stroke, there is no established therapy, particularly not for the acute stage. METHODS: In a randomized controlled trial, we compared the combined treatment of hemifield eye patching and repetitive optokinetic stimulation in acute stroke patients with neglect to the spontaneous course. Outcome measures were a neuropsychological test battery for neglect as well as scales of functional independence and clinical impairment. Outcomes were assessed at baseline (day 1), post treatment (day 8), and at 1-month follow-up (day 30). RESULTS: Final analysis included 21 acute right hemisphere stroke patients with neglect (23 enrolled, 2 lost to follow-up) allocated either to the treatment (1 week hemifield eye patching and daily sessions of optokinetic stimulation, n=11) or the control group (no neglect-specific treatment, n=10). At baseline, both groups did not differ in neuropsychological test performance, clinical impairment, or functional disability. At the post treatment session, both groups had improved in all these measures, and results were stable or further improved at follow-up. However, there was no significant difference in this change between the treatment and the control group. CONCLUSIONS: An early intervention of combined hemifield eye patching and optokinetic stimulation in acute stroke patients with spatial neglect has no additive effect to the spontaneous remitting course of the disorder. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01617343.