Transcranial direct current stimulation (tDCS) has been proposed for experimental and therapeutic modulation of regional brain function. Specifically, anodal tDCS of the dorsolateral prefrontal ...cortex (DLPFC) together with cathodal tDCS of the supraorbital region have been associated with improvement of cognition and mood, and have been suggested for the treatment of several neurological and psychiatric disorders. Although modeled mathematically, the distribution, direction, and extent of tDCS-mediated effects on brain physiology are not well understood. The current study investigates whether tDCS of the human prefrontal cortex modulates resting-state network (RSN) connectivity measured by functional magnetic resonance imaging (fMRI). Thirteen healthy subjects underwent real and sham tDCS in random order on separate days. tDCS was applied for 20 min at 2 mA with the anode positioned over the left DLPFC and the cathode over the right supraorbital region. Patterns of resting-state brain connectivity were assessed before and after tDCS with 3 T fMRI, and changes were analyzed for relevant networks related to the stimulation-electrode localizations. At baseline, four RSNs were detected, corresponding to the default mode network (DMN), the left and right frontal-parietal networks (FPNs) and the self-referential network. After real tDCS and compared with sham tDCS, significant changes of regional brain connectivity were found for the DMN and the FPNs both close to the primary stimulation site and in connected brain regions. These findings show that prefrontal tDCS modulates resting-state functional connectivity in distinct functional networks of the human brain.
Abstract Cognitive remediation therapy (CRT) is a non biological treatment that aims to correct cognitive deficits through repeated exercises. Its efficacy in patients with schizophrenia is well ...recognized, but little is known about its effect on cerebral activity. Our aim was to explore the impact of CRT on cerebral activation using functional magnetic resonance imaging (fMRI) in patients with schizophrenia. Seventeen patients and 15 healthy volunteers were recruited. Patients were divided into two groups: one group received CRT with Rehacom® software ( n = 8), while a control group of patients (non-CRT group) received no additional treatment ( n = 9). The three groups underwent two fMRI sessions with an interval of 3 months: they had to perform a verbal and a spatial n-back task at the same performance level. Patients were additionally clinically and cognitively assessed before and after the study. After CRT, the CRT group exhibited brain over-activations in the left inferior/middle frontal gyrus, cingulate gyrus and inferior parietal lobule for the spatial task. Similar but nonsignificant over-activations were observed in the same brain regions for the verbal task. Moreover, CRT patients significantly improved their behavioural performance in attention and reasoning capacities. We conclude that CRT leads to measurable physiological adaptation associated with improved cognitive ability. Trial name: Cognitive Remediation Theraphy and Schizophrenia. http://clinicaltrials.gov/ct2/show/NCT01078129. Registration number: NCT01078129.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cognitive remediation therapy (CRT) is a non biological treatment that aims to correct cognitive deficits through repeated exercises. Its efficacy in patients with schizophrenia is well recognized, ...but little is known about its effect on cerebral activity. Our aim was to explore the impact of CRT on cerebral activation using functional magnetic resonance imaging (fMRI) in patients with schizophrenia. Seventeen patients and 15 healthy volunteers were recruited. Patients were divided into two groups: one group received CRT with Rehacom® software (n=8), while a control group of patients (non-CRT group) received no additional treatment (n=9). The three groups underwent two fMRI sessions with an interval of 3months: they had to perform a verbal and a spatial n-back task at the same performance level. Patients were additionally clinically and cognitively assessed before and after the study. After CRT, the CRT group exhibited brain over-activations in the left inferior/middle frontal gyrus, cingulate gyrus and inferior parietal lobule for the spatial task. Similar but nonsignificant over-activations were observed in the same brain regions for the verbal task. Moreover, CRT patients significantly improved their behavioural performance in attention and reasoning capacities. We conclude that CRT leads to measurable physiological adaptation associated with improved cognitive ability. Trial name: Cognitive Remediation Theraphy and Schizophrenia. http://clinicaltrials.gov/ct2/show/NCT01078129.
NCT01078129.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract We aimed to identify and compare cerebral activations in schizophrenia patients and controls during a working memory (WM) task at the same performance level for both a verbal and a spatial ...task. Whereas the performances of the patients (n = 22) and controls (n = 15) were similar, cerebral activations were significantly increased in the patients, particularly in the thalamus/basal ganglia for the two tasks and in regions of the prefrontal cortex and the cerebellum for the spatial task only. Our results suggest that stronger activations of deep brain structures in patients may be the result from a compensating mechanism for WM difficulties.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Malgré le développement de nouvelles générations d’antipsychotiques, certains symptômes schizophréniques ne répondent pas à ces traitements. S’appuyant sur des hypothèses physiopathologiques sous ...tendant ces symptômes, de nouvelles thérapeutiques comme la thérapie de remédiation cognitive et les techniques de neurostimulation externe ont été développées. Cette approche était restée essentiellement clinique. Dans ce travail, l’étude en imagerie des mécanismes biologiques sous tendant les effets bénéfiques de ces thérapeutiques non pharmacologiques nous a permis de tester des hypothèses physiopathologiques. L’IRM fonctionnelle (IRMf) et la spectroscopie par résonance magnétique (SRM) ont été utilisées pour rechercher les effets d’une thérapie de remédiation cognitive (TRC), de la stimulation magnétique transcrânienne (TMS) et de la stimulation électrique transcrânienne en courant continu (tDCS). Nous avons mis en évidence (1) que la TRC modifie les activations cérébrales durant une tâche de mémoire de travail chez des patients schizophrènes (2) que la TMS modifie la biochimie cérébrale de la zone stimulée et de régions cérébrales profondes chez un patient schizophrène, (3) que la tDCS modifie les réseaux de connectivité fonctionnelle d’une tâche de repos chez des volontaires sains
Despite the development of new generation antipsychotic drugs, some symptoms of schizophrenia do not respond to these treatments. Based on the pathophysiological hypothesis underlying these symptoms, new therapies such as cognitive remediation therapy and neurostimulation techniques have been developed. This approach remained essentially clinical. In this work, the study of biological mechanisms tending benefits of these non-pharmacological treatment has allowed us to test these pathophysiological hypotheses. Functional MRI (fMRI) and magnetic resonance spectroscopy (MRS) were used to investigate the effects of cognitive remediation therapy (CRT), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). We demonstrated (1) that CRT modifies cerebral activations during a working memory task in patients with schizophrenia, (2) that TMS modifies brain biochemistry of the stimulated area and of deep brain regions in a patient with schizophrenia and (3) that tDCS modifies the functional connectivity in resting state networks of healthy volunteers
When determining optimal treatment regimens, patient reported outcomes including satisfaction are increasingly appreciated. It is well established that the birth experience may affect the postnatal ...attachment to the newborn and the management of subsequent pregnancies and deliveries. As we have no robust validated Danish tool to evaluate the childbirth experience exists, we aimed to perform a transcultural adaptation of the Childbirth Experience Questionnaire (CEQ) to a Danish context.
In accordance with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN), we translated the Swedish-CEQ to Danish. The Danish-CEQ was tested for content validity among 10 new mothers. In a population of women who have had their labour induced, we then assessed the electronic questionnaire for validity and reliability using factor analytical design, hypothesis testing, and internal consistency. Based on these data, we determined criterion and construct responsiveness in addition to floor and ceiling effects.
The content validation resulted in minor adjustments in two items. This improved the comprehensibility. The electronic questionnaire was completed by 377 of 495 women (76.2%). The original Swedish-CEQ was four-dimensional, however an exploratory factor analysis revealed a three-dimensional structure in our Danish population (Own capacity, Participation, and Professional support). Parous women, women who delivered vaginally, and women with a labour duration <12 hours had a higher score in each domain. The internal consistency (Cronbach's alpha) ranged between 0.75 and 0.89 and the ICC between 0.68-0.93. We found ceiling effects of 57.6% in the domain Professional support and of 25.5% in the domain Participation.
This study offers transcultural adaptation of the Swedish-CEQ to a Danish context. The 3-dimensional Danish-CEQ demonstrates construct validity and reliability. Our results revealed significant ceiling effect especially in the domain Professional support, which needs to be acknowledged when considering implementing the Danish-CEQ into trials and clinical practice.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Targeted therapies have yet to have significant impact on the survival of patients with bladder cancer. In this study, we focused on the urea cycle enzyme argininosuccinate synthetase 1 (ASS1) as a ...therapeutic target in bladder cancer, based on our discovery of the prognostic and functional import of ASS1 in this setting. ASS1 expression status in bladder tumors from 183 Caucasian and 295 Asian patients was analyzed, along with its hypothesized prognostic impact and association with clinicopathologic features, including tumor size and invasion. Furthermore, the genetics, biology, and therapeutic implications of ASS1 loss were investigated in urothelial cancer cells. We detected ASS1 negativity in 40% of bladder cancers, in which multivariate analysis indicated worse disease-specific and metastasis-free survival. ASS1 loss secondary to epigenetic silencing was accompanied by increased tumor cell proliferation and invasion, consistent with a tumor-suppressor role for ASS1. In developing a treatment approach, we identified a novel targeted antimetabolite strategy to exploit arginine deprivation with pegylated arginine deiminase (ADI-PEG20) as a therapeutic. ADI-PEG20 was synthetically lethal in ASS1-methylated bladder cells and its exposure was associated with a marked reduction in intracellular levels of thymidine, due to suppression of both uptake and de novo synthesis. We found that thymidine uptake correlated with thymidine kinase-1 protein levels and that thymidine levels were imageable with (18)F-fluoro-L-thymidine (FLT)-positron emission tomography (PET). In contrast, inhibition of de novo synthesis was linked to decreased expression of thymidylate synthase and dihydrofolate reductase. Notably, inhibition of de novo synthesis was associated with potentiation of ADI-PEG20 activity by the antifolate drug pemetrexed. Taken together, our findings argue that arginine deprivation combined with antifolates warrants clinical investigation in ASS1-negative urothelial and related cancers, using FLT-PET as an early surrogate marker of response.
Ponseti clubfoot treatment has become more popular during the last decade. We reviewed the medical records of 74 consecutive infants (117 club feet) who underwent Ponseti treatment. Minimum followup ...was 5 years (mean, 6.3 years; range, 5–9 years). We studied age at presentation, previous treatment, the initial severity score of the Pirani scoring system, number of casts, need for Achilles tenotomy or other surgical procedures, and brace use. We measured final ankle motion and parents’ perception of outcome. Late presentation and previous non-Ponseti treatment were associated with lower initial severity score, fewer casts, and less need for tenotomy. Forty-four percent of patients had poor brace use. We observed better brace use (75%) in babies who presented late for treatment. Good brace use predicted less need for extensive surgical procedures. Twenty-four (32%) babies underwent additional surgical procedures other than tenotomy, including 21% who underwent tibialis anterior tendon transfer. At followup, 89% of feet had adequate dorsiflexion (5° or greater). Parents indicated high satisfaction with the treatment results. Ankle motion was not associated with parents’ satisfaction. The Ponseti method is effective, even if treatment starts late or begins after failure at other centers. Brace use influenced the success of treatment.
Level of Evidence:
Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UL, UM, UPUK, VKSCE, ZAGLJ
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