Jacobus F.A. Jansen

Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures.

Introduction Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but lack epileptiform brain activity. Instead, the cause is assumed to be psychogenic. An abnormal coping strategy may be exhibited by PNES patients, as indicated by their increased tendency to dissociate. Investigation of resting-state networks may reveal altered routes of information and emotion processing in PNES patients. The authors therefore investigated whether PNES patients differ from healthy controls in their resting-state functional connectivity characteristics and whether these connections are associated with the tendency to dissociate. Methods 11 PNES patients without psychiatric comorbidity and 12 healthy controls underwent task-related paradigms (picture-encoding and Stroop paradigms) and resting-state functional MRI (rsfMRI). Global cognitive performance was tested using the Ravens Matrices test and participants completed questionnaires for evaluating dissociation. Functional connectivity analysis on rsfMRI was based on seed regions extracted from task-related fMRI activation maps. Results The patients displayed a significantly lower cognitive performance and significantly higher dissociation scores. No significant differences were found between the picture-encoding and Stroop colour-naming activation maps between controls and patients with PNES. However, functional connectivity maps from the rsfMRI were statistically different. For PNES patients, stronger connectivity values between areas involved in emotion (insula), executive control (inferior frontal gyrus and parietal cortex) and movement (precentral sulcus) were observed, which were significantly associated with dissociation scores. Conclusion The abnormal, strong functional connectivity in PNES patients provides a neurophysiological correlate for the underlying psychoform and somatoform dissociation mechanism where emotion can influence executive control, resulting in altered motor function (eg, seizure-like episodes).

Loss of network efficiency associated with cognitive decline in chronic epilepsy.

Objective: To study the relation between possibly altered whole brain topology and intellectual decline in chronic epilepsy, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI was performed. Methods: Forty-one adult patients with cryptogenic localization-related epilepsy and 23 healthy controls underwent an intelligence test and fMRI with a silent-word generation paradigm. A set of undirected graphs was constructed by cross-correlating the signal time series of 893 cortical and subcortical regions. Possible changes in cerebral network efficiency were assessed by performing graph theoretical network analysis. Results: Healthy subjects displayed efficient small world properties, characterized by high clustering and short path lengths. On the contrary, in patients with epilepsy a disruption of both local segregation and global integration was found. An association of more pronounced intellectual decline with more disturbed local segregation was observed in the patient group. The effect of antiepileptic drug use on cognitive decline was mediated by decreased clustering. Conclusions: These findings support the hypothesis that chronic localization-related epilepsy causes cognitive deficits by inducing global cerebral network changes instead of a localized disruption only. Whether this is the result of epilepsy per se or the use of antiepileptic drugs remains to be elucidated. For application in clinical practice, future studies should address the relevance of altered cerebral network topology in prediction of cognitive deficits and monitoring of therapeutic interventions.

The effect and reproducibility of different clinical DTI gradient sets on small world brain connectivity measures

Advances in computational network analysis have enabled the characterization of topological properties in large scale networks including the human brain. Information on structural networks in the brain can be obtained in-vivo by performing tractography on diffusion tensor imaging (DTI) data. However, little is known about the reproducibility of network properties derived from whole brain tractography data, which has important consequences for minimally detectable abnormalities or changes over time. Moreover, acquisition parameters, such as the number of gradient directions and gradient strength, possibly influence network metrics and the corresponding reproducibility derived from tractography data. The aim of the present study is twofold: (i) to determine the effect of several clinically available DTI sampling schemes, differing in number of gradient directions and gradient amplitude, on small world metrics and (ii) to evaluate the interscan reproducibility of small world metrics. DTI experiments were conducted on six healthy volunteers scanned twice. Probabilistic tractography was performed to reconstruct structural connections between regions defined from an anatomical atlas. The observed reproducibility of the network measures was high, reflected by low values for the coefficient of variation (<3.8%), advocating the use of graph theoretical measurements to study neurological diseases. Small world metrics were dependent on the choice of DTI gradient scheme and showed stronger connectivity with increasing directional resolution. The interscan reproducibility was not dependent on the gradient scheme. These findings should be considered when comparing results across studies using different gradient schemes or designing new studies.

White Matter Network Abnormalities Are Associated with Cognitive Decline in Chronic Epilepsy

Patients with chronic epilepsy frequently display cognitive comorbidity and might have widespread network abnormalities outside the epileptic zone, which might affect a variety of cognitive functions and global intelligence. We aimed to study the role of white matter connectivity in cognitive comorbidity. Thirty-nine patients with nonsymptomatic localization-related epilepsy and varying degrees of cognitive impairment and 23 age-matched healthy controls were included. Whole brain white matter networks were constructed from fiber tractography. Weighted graph theoretical analysis was performed to study white matter network abnormalities associated with epilepsy and cognition. Patients with severe cognitive impairment showed lower clustering (a measure of brain network segregation) and higher path length (a measure of brain network integration) compared with the healthy controls and patients with little or no cognitive impairment, whereas whole brain white matter volume did not differ. Correlation analyses revealed that IQ and cognitive impairment were strongly associated with clustering and path lengths. This study revealed impaired white matter connectivity, associated with cognitive comorbidity in patients with chronic epilepsy. As whole brain white matter volumes were preserved in the patient group, our results suggest an important role for the network topology rather than volumetric changes, in epilepsy with cognitive decline.

Noninvasive Assessment of Tumor Microenvironment Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging and 18F-Fluoromisonidazole Positron Emission Tomography Imaging in Neck Nodal Metastases

PURPOSE To assess noninvasively the tumor microenvironment of neck nodal metastases in patients with head-and-neck cancer by investigating the relationship between tumor perfusion measured using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and hypoxia measured by (18)F-fluoromisonidazole ((18)F-FMISO) positron emission tomography (PET). METHODS AND MATERIALS Thirteen newly diagnosed head-and-neck cancer patients with metastatic neck nodes underwent DCE-MRI and (18)F-FMISO PET imaging before chemotherapy and radiotherapy. The matched regions of interests from both modalities were analyzed. To examine the correlations between DCE-MRI parameters and standard uptake value (SUV) measurements from (18)F-FMISO PET, the nonparametric Spearman correlation coefficient was calculated. Furthermore, DCE-MRI parameters were compared between nodes with (18)F-FMISO uptake and nodes with no (18)F-FMISO uptake using Mann-Whitney U tests. RESULTS For the 13 patients, a total of 18 nodes were analyzed. The nodal size strongly correlated with the (18)F-FMISO SUV (rho = 0.74, p < 0.001). There was a strong negative correlation between the median k(ep) (redistribution rate constant) value (rho = -0.58, p = 0.042) and the (18)F-FMISO SUV. Hypoxic nodes (moderate to severe (18)F-FMISO uptake) had significantly lower median K(trans) (volume transfer constant) (p = 0.049) and median k(ep) (p = 0.027) values than did nonhypoxic nodes (no (18)F-FMISO uptake). CONCLUSION This initial evaluation of the preliminary results support the hypothesis that in metastatic neck lymph nodes, hypoxic nodes are poorly perfused (i.e., have significantly lower K(trans) and k(ep) values) compared with nonhypoxic nodes.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Predictor of Outcome in Head-and-Neck Squamous Cell Carcinoma Patients With Nodal Metastases

PURPOSE Dynamic contrast-enhanced MRI (DCE-MRI) can provide information regarding tumor perfusion and permeability and has shown prognostic value in certain tumors types. The goal of this study was to assess the prognostic value of pretreatment DCE-MRI in head and neck squamous cell carcinoma (HNSCC) patients with nodal disease undergoing chemoradiation therapy or surgery. METHODS AND MATERIALS Seventy-four patients with histologically proven squamous cell carcinoma and neck nodal metastases were eligible for the study. Pretreatment DCE-MRI was performed on a 1.5T MRI. Clinical follow-up was a minimum of 12 months. DCE-MRI data were analyzed using the Tofts model. DCE-MRI parameters were related to treatment outcome (progression-free survival [PFS] and overall survival [OS]). Patients were grouped as no evidence of disease (NED), alive with disease (AWD), dead with disease (DOD), or dead of other causes (DOC). Prognostic significance was assessed using the log-rank test for single variables and Cox proportional hazards regression for combinations of variables. RESULTS At last clinical follow-up, for Stage III, all 12 patients were NED. For Stage IV, 43 patients were NED, 4 were AWD, 11 were DOD, and 4 were DOC. K(trans) is volume transfer constant. In a stepwise Cox regression, skewness of K(trans) (volume transfer constant) was the strongest predictor for Stage IV patients (PFS and OS: p <0.001). CONCLUSION Our study shows that skewness of K(trans) was the strongest predictor of PFS and OS in Stage IV HNSCC patients with nodal disease. This study suggests an important role for pretreatment DCE-MRI parameter K(trans) as a predictor of outcome in these patients.

Working memory deficits in high-functioning adolescents with autism spectrum disorders: neuropsychological and neuroimaging correlates

Working memory is a temporary storage system under attentional control. It is believed to play a central role in online processing of complex cognitive information and may also play a role in social cognition and interpersonal interactions. Adolescents with a disorder on the autism spectrum display problems in precisely these domains. Social impairments, communication difficulties, and repetitive interests and activities are core domains of autism spectrum disorders (ASD), and executive function problems are often seen throughout the spectrum. As the main cognitive theories of ASD, including the theory of mind deficit hypotheses, weak central coherence account, and the executive dysfunction theory, still fail to explain the broad spectrum of symptoms, a new perspective on the etiology of ASD is needed. Deficits in working memory are central to many theories of psychopathology, and are generally linked to frontal-lobe dysfunction. This article will review neuropsychological and (functional) brain imaging studies on working memory in adolescents with ASD. Although still disputed, it is concluded that within the working memory system specific problems of spatial working memory are often seen in adolescents with ASD. These problems increase when information is more complex and greater demands on working memory are made. Neuroimaging studies indicate a more global working memory processing or connectivity deficiency, rather than a focused deficit in the prefrontal cortex. More research is needed to relate these working memory difficulties and neuroimaging results in ASD to the behavioral difficulties as seen in individuals with a disorder on the autism spectrum.

Non-gaussian analysis of diffusion-weighted MR imaging in head and neck squamous cell carcinoma: A feasibility study.

BACKGROUND AND PURPOSE: Water in biological structures often displays non-Gaussian diffusion behavior. The objective of this study was to test the feasibility of non-Gaussian fitting by using the kurtosis model of the signal intensity decay curves obtained from DWI by using an extended range of b-values in studies of phantoms and HNSCC. MATERIALS AND METHODS: Seventeen patients with HNSCC underwent DWI by using 6 b-factors (0, 50–1500 s/mm2) at 1.5T. Monoexponential (yielding ADCmono) and non-Gaussian kurtosis (yielding apparent diffusion coefficient Dapp and apparent kurtosis coefficient Kapp) fits were performed on a voxel-by-voxel basis in selected regions of interest (primary tumors, metastatic lymph nodes, and spinal cord). DWI studies were also performed on phantoms containing either water or homogenized asparagus. To determine whether the kurtosis model provided a significantly better fit than did the monoexponential model, an F test was performed. Spearman correlation coefficients were calculated to assess correlations between Kapp and Dapp. RESULTS: The kurtosis model fit the experimental data points significantly better than did the monoexponential model (P < .05). Dapp was approximately twice the value of ADCmono (eg, in neck nodal metastases Dapp was 1.54 and ADCmono was 0.84). Kapp showed a weak Spearman correlation with Dapp in a homogenized asparagus phantom and for 44% of tumor lesions. CONCLUSIONS: The use of kurtosis modeling to fit DWI data acquired by using an extended b-value range in HNSCC is feasible and yields a significantly better fit of the data than does monoexponential modeling. It also provides an additional parameter, Kapp, potentially with added value.

Percutaneous pulsed radiofrequency treatment of the cervical dorsal root ganglion in the treatment of chronic cervical pain syndromes: a clinical audit.

Cervicogenic headache and cervicobrachialgia are frequent diagnoses of chronic cervical pain. After failure of conservative treatment, an interventional approach may be indicated in the absence of any indication for causal surgical treatment. The pulsed radiofrequency (PRF) technique exposes the nerve to a high‐frequency electric field while the temperature of the electrode tip does not exceed 42°C. This method is thought to be nondestructive and almost free of neurologic side effects and complications. Our extended pilot study was performed to confirm the perceived efficacy of PRF for short‐ and long‐term relief of chronic cervical pain. We carried out a clinical audit of the first 18 patients treated with PRF at the cervical dorsal root ganglion. An independent evaluator reviewed the medical records. Patients with good clinical results at 8 weeks were evaluated for long‐term effect (> 6 months), based on a 7‐point Likert scale. Thirteen patients (72%) showed short‐term clinical success (≥ 50% pain relief). Mean follow‐up was 19.4 months (SD 8.9 months), maximum 2.5 years. The duration of satisfactory pain relief (6 or 7 on the Likert scale) varied between 2 and over 30 months, with a mean duration of 9.2 months (SD 11.2 months). Kaplan‐Meier analysis illustrated that 50% of patients experienced success 3 months after treatment. We could not identify predictive variables for clinical outcome. None of the patients reported post‐treatment neuritis or other adverse events. To our knowledge, this is the first documented series of chronic cervical pain syndromes treated with PRF. Satisfactory pain relief of at least 50% was achieved in 13 of 18 (72%) patients at 8 weeks. More than one year after treatment, six patients (33%) continue to rate treatment outcome as good or very good. No side effects were reported. j

Tumor Metabolism and Perfusion in Head and Neck Squamous Cell Carcinoma: Pretreatment Multimodality Imaging with 1H-Magnetic Resonance Spectroscopy, Dynamic Contrast-Enhanced MRI and 18F-FDG PET

PURPOSE To correlate proton magnetic resonance spectroscopy ((1)H-MRS), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and (18)F-labeled fluorodeoxyglucose positron emission tomography ([(18)F]FDG PET) of nodal metastases in patients with head and neck squamous cell carcinoma (HNSCC) for assessment of tumor biology. Additionally, pretreatment multimodality imaging was evaluated for its efficacy in predicting short-term response to treatment. METHODS AND MATERIALS Metastatic neck nodes were imaged with (1)H-MRS, DCE-MRI, and [(18)F]FDG PET in 16 patients with newly diagnosed HNSCC, before treatment. Short-term patient radiological response was evaluated at 3 to 4 months. Correlations among (1)H-MRS (choline concentration relative to water [Cho/W]), DCE-MRI (volume transfer constant [K(trans)]; volume fraction of the extravascular extracellular space [v(e)]; and redistribution rate constant [k(ep)]), and [(18)F]FDG PET (standard uptake value [SUV] and total lesion glycolysis [TLG]) were calculated using nonparametric Spearman rank correlation. To predict short-term responses, logistic regression analysis was performed. RESULTS A significant positive correlation was found between Cho/W and TLG (ρ = 0.599; p = 0.031). Cho/W correlated negatively with heterogeneity measures of standard deviation std(v(e)) (ρ = -0.691; p = 0.004) and std(k(ep)) (ρ = -0.704; p = 0.003). Maximum SUV (SUVmax) values correlated strongly with MRI tumor volume (ρ = 0.643; p = 0.007). Logistic regression indicated that std(K(trans)) and SUVmean were significant predictors of short-term response (p < 0.07). CONCLUSION Pretreatment multimodality imaging using (1)H-MRS, DCE-MRI, and [(18)F]FDG PET is feasible in HNSCC patients with nodal metastases. Additionally, combined DCE-MRI and [(18)F]FDG PET parameters were predictive of short-term response to treatment.