Processing of Positive Visual Stimuli Before and After Symptoms Provocation in Posttraumatic Stress Disorder - A Functional Magnetic Resonance Imaging Study of Trauma-Affected Male Refugees.

BACKGROUND: Symptoms of anhedonia are often central to posttraumatic stress disorder (PTSD), but it is unclear how anhedonia is affected by processes induced by reliving past traumatic memories. METHODS: Sixty-nine male refugees (PTSD = 38) were interviewed and scanned with functional magnetic resonance imaging while viewing positive, neutral and Scrambled Pictures after being read personalized scripts evoking an emotionally neutral memory and a traumatic memory. We further measured postprovocation state symptoms, physiological measures and PTSD symptoms. We tested whether neural activity associated with positive picture viewing in participants with PTSD was differentially affected by symptom provocation compared to controls. RESULTS: For the pictures > scrambled contrast (Positive contrast), PTSD participants had significantly less activity than controls in fusiform gyrus, right inferior temporal gyrus and left middle occipital gyrus. The Positive contrast activity in fusiform gyrus scaled negatively with anhedonia symptoms in PTSD participants after controlling for total PTSD severity. Relative to the emotionally Neutral Script, the Trauma Script decreased positive picture viewing activity in posterior cingulate cortex, precuneus and left calcarine gyrus, but there was no difference between PTSD participants and controls. CONCLUSIONS: We found reduced responsiveness of higher visual processing of emotionally positive pictures in PTSD. The significant correlation found between positive picture viewing activity and anhedonia suggests the reduced responsiveness to be due to the severity of anhedonia.

Associations of neural processing of reward with posttraumatic stress disorder and secondary psychotic symptoms in trauma-affected refugees.

Background: Psychological traumatic experiences can lead to posttraumatic stress disorder (PTSD). Secondary psychotic symptoms are not common but may occur. Objectives: Since psychotic symptoms of schizophrenia have been related to aberrant reward processing in the striatum, using the same paradigm we investigate whether the same finding extends to psychotic and anhedonic symptoms in PTSD. Methods: A total of 70 male refugees: 18 PTSD patients with no secondary psychotic symptoms (PTSD-NSP), 21 PTSD patients with secondary psychotic symptoms (PTSD-SP), and 31 healthy controls (RHC) were interviewed and scanned with functional magnetic resonance imaging (fMRI) during a monetary incentive delay task. Using region of interest analysis of the prefrontal cortex and ventral striatum, we investigated reward-related activity. Results: Compared to RHC, participants with PTSD had decreased neural activity during monetary reward. Also, participants with PTSD-SP exhibited decreased activity in the associative striatum relative to participants with PTSD-NSP during processing of motivational reward anticipation which correlated with severity of psychotic symptoms. However, the difference between the two PTSD groups disappeared when PTSD severity and trauma exposure were accounted for. Conclusions: Anhedonia and secondary psychotic symptoms in PTSD are characterized by dysfunctional reward consumption and anticipation processing, respectively. The latter may reflect a mechanism by which abnormal reward signals in the basal ganglia facilitates psychotic symptoms across psychiatric conditions.

Antecedentes: Las experiencias traumáticas psicológicas pueden conducir al trastorno de estrés postraumático (TEPT). Los síntomas psicóticos secundarios no son comunes, pero pueden ocurrir.Objetivos: Dado que los síntomas psicóticos de la esquizofrenia se han relacionado con el procesamiento aberrante de recompensas en el cuerpo estriado, utilizando el mismo paradigma, investigamos si el mismo hallazgo se extiende a los síntomas psicóticos y anhedónicos en el TEPT.Método: Un total de 70 refugiados varones: 18 pacientes con TEPT sin síntomas psicóticos secundarios (TEPT-NSP), 21 pacientes con TEPT con síntomas psicóticos secundarios (TEPT-SP) y 31 controles sanos (RHC) fueron entrevistados y escaneados con Imagen por resonancia magnética funcional (fMRI en su sigla en inglés) durante una tarea de retraso de incentivo monetario. Mediante el análisis de la región de interés de la corteza prefrontal y el estriado ventral, investigamos la actividad relacionada con la recompensa.Resultados: En comparación con los RHC, los participantes con TEPT habían disminuido la actividad neuronal durante la recompensa monetaria. Además, los participantes con TEPT-SP exhibieron disminución de la actividad en el estriado asociativo en relación con los participantes con TEPT-NSP durante el procesamiento de la anticipación de recompensa motivacional, lo cual estuvo correlacionado con la gravedad de los síntomas psicóticos. Sin embargo, la diferencia entre los dos grupos de TEPT desapareció cuando se controlaron la gravedad del TEPT y la exposición al trauma.Conclusiones: La anhedonia y los síntomas psicóticos secundarios en el TEPT se caracterizan por un consumo de recompensa disfuncional y un procesamiento de anticipación, respectivamente. Este último puede reflejar un mecanismo por el cual las señales de recompensa anormales en los ganglios basales facilitan los síntomas psicóticos a través de afecciones psiquiátricas.

Diagnostic added value of electrical source imaging in presurgical evaluation of patients with epilepsy: A prospective study.

OBJECTIVE: To investigate the diagnostic added value of electrical source imaging (ESI) in presurgical evaluation of patients with drug resistant focal epilepsy. METHODS: Eighty-two consecutive patients were included. We analyzed both low density (LD) and high density (HD) EEG recordings. LD ESI was done on interictal and ictal signals recorded during long-term video-EEG monitoring (LTM), with standard 25 electrodes and age-matched template head models. HD ESI was done on shorter recordings (90-120 min), with 256 electrodes, using individual head model. The multidisciplinary team made decisions first blinded to ESI (based on all other modalities) and then discussed the results of the ESI. We considered that ESI had diagnostic added value, when it provided non-redundant information that changed the patients management plan. RESULTS: ESI had diagnostic added value in 28 patients (34%). In most cases (85.7%), these changes were related to planning of the invasive recordings. In nine out of 13 patients, invasive recordings confirmed the localization. Out of eight patients in whom the ESI source was resected, six became seizure-free. CONCLUSIONS: ESI provides non-redundant information in one third of the patients undergoing presurgical evaluation. SIGNIFICANCE: This study provides evidence for the diagnostic added value of ESI in presurgical evaluation.

Electromagnetic source imaging in presurgical workup of patients with epilepsy: A prospective study.

OBJECTIVE: To determine the diagnostic accuracy and clinical utility of electromagnetic source imaging (EMSI) in presurgical evaluation of patients with epilepsy. METHODS: We prospectively recorded magnetoencephalography (MEG) simultaneously with EEG and performed EMSI, comprising electric source imaging, magnetic source imaging, and analysis of combined MEG-EEG datasets, using 2 different software packages. As reference standard for irritative zone (IZ) and seizure onset zone (SOZ), we used intracranial recordings and for localization accuracy, outcome 1 year after operation. RESULTS: We included 141 consecutive patients. EMSI showed localized epileptiform discharges in 94 patients (67%). Most of the epileptiform discharge clusters (72%) were identified by both modalities, 15% only by EEG, and 14% only by MEG. Agreement was substantial between inverse solutions and moderate between software packages. EMSI provided new information that changed the management plan in 34% of the patients, and these changes were useful in 80%. Depending on the method, EMSI had a concordance of 53% to 89% with IZ and 35% to 73% with SOZ. Localization accuracy of EMSI was between 44% and 57%, which was not significantly different from MRI (49%-76%) and PET (54%-85%). Combined EMSI achieved significantly higher odds ratio compared to electric source imaging and magnetic source imaging. CONCLUSION: EMSI has accuracy similar to established imaging methods and provides clinically useful, new information in 34% of the patients. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that EMSI had a concordance of 53%-89% and 35%-73% (depending on analysis) for the localization of epileptic focus as compared with intracranial recordings-IZ and SOZ, respectively.

Automated EEG source imaging: A retrospective, blinded clinical validation study.

OBJECTIVE: To evaluate the accuracy of automated EEG source imaging (ESI) in localizing epileptogenic zone. METHODS: Long-term EEG, recorded with the standard 25-electrode array of the IFCN, from 41 consecutive patients with focal epilepsy who underwent resective surgery, were analyzed blinded to the surgical outcome. The automated analysis comprised spike-detection, clustering and source imaging at the half-rising time and at the peak of each spike-cluster, using individual head-models with six tissue-layers and a distributed source model (sLORETA). The fully automated approach presented ESI of the cluster with the highest number of spikes, at the half-rising time. In addition, a physician involved in the presurgical evaluation of the patients, evaluated the automated ESI results (up to four clusters per patient) in clinical context and selected the dominant cluster and the analysis time-point (semi-automated approach). The reference standard was location of the resected area and outcome one year after operation. RESULTS: Accuracy was 61% (95% CI: 45-76%) for the fully automated approach and 78% (95% CI: 62-89%) for the semi-automated approach. CONCLUSION: Automated ESI has an accuracy similar to previously reported neuroimaging methods. SIGNIFICANCE: Automated ESI will contribute to increased utilization of source imaging in the presurgical evaluation of patients with epilepsy.

[Epilepsy surgery].

Surgery is the only treatment option with the potential to cure epilepsy. This review is a description of the multidisciplinary and multimodal presurgical evaluation process and the outcome of the Danish epilepsy surgery programme. The outcome aligns with international results and serious complications to surgery are very rare. The annual number of operations per capita compares to neighbouring countries and is equally distributed across Denmark. In accordance with international recommendations, Danish drug-resistant patients should be referred to epilepsy surgery evaluation at an early stage of the disease.

Congenital olfactory impairment is linked to cortical changes in prefrontal and limbic brain regions.

The human sense of smell is closely associated with morphological differences of the fronto-limbic system, specifically the piriform cortex and medial orbitofrontal cortex (mOFC). Still it is unclear whether cortical volume in the core olfactory areas and connected brain regions are shaped differently in individuals who suffer from lifelong olfactory deprivation relative to healthy normosmic individuals. To address this question, we examined if regional variations in gray matter volume were associated with smell ability in seventeen individuals with isolated congenital olfactory impairment (COI) matched with sixteen normosmic controls. All subjects underwent whole-brain magnetic resonance imaging, and voxel-based morphometry was used to estimate regional variations in grey matter volume. The analyses showed that relative to controls, COI subjects had significantly larger grey matter volumes in left middle frontal gyrus and right superior frontal sulcus (SFS). COI subjects with severe olfactory impairment (anosmia) had reduced grey matter volume in the left mOFC and increased volume in right piriform cortex and SFS. Within the COI group olfactory ability, measured with the "Sniffin' Sticks" test, was positively associated with larger grey matter volume in right posterior cingulate and parahippocampal cortices whereas the opposite relationship was observed in controls. Across COI subjects and controls, better olfactory detection threshold was associated with smaller volume in right piriform cortex, while olfactory identification was negatively associated with right SFS volume. Our findings suggest that lifelong olfactory deprivation trigger changes in the cortical volume of prefrontal and limbic brain regions previously linked to olfactory memory.

Clinically silent PML and prolonged immune reconstitution inflammatory syndrome in a patient with multiple sclerosis treated with natalizumab.

We report the case of a woman with natalizumab-treated multiple sclerosis (MS) and clinically silent progressive multifocal leukoencephalopathy (PML) with an unusually long preclinical phase, followed by acute symptoms due to development of immune reconstitution inflammatory syndrome (IRIS). Furthermore, the course of the IRIS was prolonged and continued to progress even five months after natalizumab treatment was ceased. This case shows that PML and IRIS can have a considerably variable course in natalizumab-treated MS patients and underlines the need for PML screening in JC virus antibody-positive patients in order to detect clinically silent cases.

White matter hyperintensities and prepulse inhibition in a mixed elderly population.

Prepulse inhibition (PPI) of the startle response, a measure for sensorimotor gating, exhibits a relatively high inter-individual variability in elderly subjects. The aim of this study was to investigate whether white matter hyperintensities (WMH), frequently identified on cranial magnetic resonance imaging (MRI) in elderly subjects with and without cognitive impairment, may contribute to variations in PPI. A passive acoustic PPI paradigm was applied in 92 human subjects (53 healthy and 39 patients with Alzheimer's disease or mild cognitive impairment) between 60 and 85years of age. WMH were rated visually on craniel MRI FLAIR images using the Fazekas scale. WMH were identified in 70% of all subjects. The latency to peak of the startle response increased significantly with increasing WMH load, whereas the inhibition of the startle response (PPI) was neither significantly related to the degree of WMH nor to cognitive performance. We conclude that the presence of WMH in the fronto-striatal brain circuit may affect the latency of the startle response, but not information processing in elderly subjects.

Corpus callosum atrophy in patients with mild Alzheimer's disease.

BACKGROUND/OBJECTIVES: Several studies have found atrophy of the corpus callosum (CC) in patients with Alzheimer's disease (AD). However, it remains unclear whether callosal atrophy is already present in the early stages of AD, and to what extent it may be associated with other structural changes in the brain, such as age-related white matter changes (ARWMC) and progression of the disease. METHODS: Twenty-eight patients in the early stages of AD and 50 non-demented elderly subjects with varying degrees of ARWMC were investigated using MRI. The CC was assessed semi-automatically, and ARWMC were rated according to the Fazekas scale. RESULTS: A significant difference in posterior CC size could be detected between non-demented elderly subjects and early stage AD patients. The sizes of the total CC, rostral body and splenium at baseline were correlated with change from baseline MMSE score after a 1-year follow-up in AD patients. There was no association between CC size and ARWMC. CONCLUSIONS: The present findings indicate that posterior CC atrophy is present in mild AD independently of ARWMC. Furthermore, CC atrophy may be associated with cognitive deterioration.

Aortic dimensions in girls and young women with turner syndrome: a magnetic resonance imaging study.

This study aimed to determine the dimensions of the thoracic aorta and the predictors of aortic dimensions in girls and young women with Turner syndrome (TS). A cross-sectional study was performed at a secondary care center. The study compared 41 TS patients with 50 healthy age-matched control subjects. The mean age of the patients was 17 +/- 3.3 years. Magnetic resonance imaging was performed for all the patients. The thoracic aortic diameters of the patients were measured at nine positions. Adjustment for body surface area (BSA) was performed. The outcome for the patients was measured in terms of absolute and BSA-adjusted aortic dilation. In TS, both the absolute and the BSA-adjusted mean aortic diameters were smaller than or comparable with those of the control subjects. However, individual aortic dilation at one to four positions was found in four TS patients according to the uncorrected data and in five TS patients after BSA-adjustment. The aortic diameters correlated with height, weight, body mass index (BMI), and BSA at all positions (R = 0.34-0.60; all p < 0.04). The diameters of the aortic arch and the descending aorta correlated with a history of aortic coarctation (R = 0.35-0.52; p < 0.03). The presence of bicuspid aortic valves correlated at the descending part of the aorta (R = 0.38; p < 0.03). The mean thoracic aortic dimensions were not enlarged in girls or young TS patients. The BSA predicted aortic size at all positions. The prevalence of aortic dilation and aneurysm was lower in this population of girls and younger women with TS than in older TS populations.

[Magnetic Resonance Imaging in the preoperative staging of rectum cancer]. / Magnetisk resonans-skanning til praeoperativ stadieinddeling af cancer recti.

INTRODUCTION: The treatment of rectum cancer depends on the tumour stage, and until 2005 treatment included preoperative radiation therapy for the T3 and T4 cancer stages. An exact preoperative assessment of the cancer stage is therefore essential. In Denmark rectal Magnetic Resonance Imaging (MRI) is used as a standard procedure in preoperative evaluation, sometimes supplemented by transrectal ultrasound (TRUS). The purpose of this study was to determine the accuracy of preoperative MRI in tumour stage evaluation in order to correctly select the patients who will benefit from preoperative radiation therapy. MATERIAL AND METHODS: The MRI reports from 173 patients (98 male, 75 female, mean age 71 years) who underwent surgery for rectum cancer at Hvidovre Hospital, Copenhagen during the 2002-2005-period were evaluated. The T-stage of the MRI report was compared to the histological T-stage of the resected tumour. RESULTS: The overall accuracy of T-staging was 58% (n = 100) of which 41% T2 tumours (n = 18), 78% T3 tumours (n = 78) and 33% T4 tumours (n = 4) were correctly staged. In all, 29% of cancers were overstaged (n = 50) (100% of T1 tumours, 59% of T2 tumours, 7% of T3 tumours). A total of 13% of the cancers were understaged (15% of T3 tumours, 67% of T4 tumours). The selection of patients for preoperative radiation therapy had a sensitivity and specificity of 83% and 48%, respectively. CONCLUSION: The overall accuracy of 58% indicates that MR imaging in the early learning phases was not an optimal method for the preoperative T-staging of rectal cancer. In particular, the low specificity of MRI in selecting the patients who will benefit from preoperative radiation can result in overtreatment and increased morbidity.