A characterization of the oscillatory activity in the cerebral cortex of the mouse was realized under ketamine anesthesia. Bilateral recordings were obtained from deep layers of primary visual, somatosensory, motor, and medial prefrontal cortex. A slow oscillatory activity consisting of up and down states was detected, the average frequency being 0.97 Hz in all areas. Different parameters of the oscillation were estimated across cortical areas, including duration of up and down states and their variability, speed of state transitions, and population firing rate. Similar values were obtained for all areas except for prefrontal cortex, which showed significant faster down-to-up state transitions, higher firing rate during up states, and more regular cycles. The wave propagation patterns in the anteroposterior axis in motor cortex and the mediolateral axis in visual cortex were studied with multielectrode recordings, yielding speed values between 8 and 93 mm/s. The firing of single units was analyzed with respect to the population activity. The most common pattern was that of neurons firing in >90% of the up states with 1-6 spikes. Finally, fast rhythms (beta, low gamma, and high gamma) were analyzed, all of them showing significantly larger power during up states than in down states. Prefrontal cortex exhibited significantly larger power in both beta and gamma bands (up to 1 order of magnitude larger in the case of high gamma) than the rest of the cortical areas. This study allows us to carry out interareal comparisons and provides a baseline to compare against cortical emerging activity from genetically altered animals.
The dual-specificity tyrosine phosphorylation-regulated kinase DYRK1A is a serine/threonine kinase involved in neuronal differentiation and synaptic plasticity and a major candidate of Down syndrome brain alterations and cognitive deficits. DYRK1A is strongly expressed in the cerebral cortex, and its overexpression leads to defective cortical pyramidal cell morphology, synaptic plasticity deficits, and altered excitation/inhibition balance. These previous observations, however, do not allow predicting how the behavior of the prefrontal cortex (PFC) network and the resulting properties of its emergent activity are affected. Here, we integrate functional, anatomical, and computational data describing the prefrontal network alterations in transgenic mice overexpressing Dyrk1A (TgDyrk1A). Using in vivo extracellular recordings, we show decreased firing rate and gamma frequency power in the prefrontal network of anesthetized and awake TgDyrk1A mice. Immunohistochemical analysis identified a selective reduction of vesicular GABA transporter punctae on parvalbumin positive neurons, without changes in the number of cortical GABAergic neurons in the PFC of TgDyrk1A mice, which suggests that selective disinhibition of parvalbumin interneurons would result in an overinhibited functional network. Using a conductance-based computational model, we quantitatively demonstrate that this alteration could explain the observed functional deficits including decreased gamma power and firing rate. Our results suggest that dysfunction of cortical fast-spiking interneurons might be central to the pathophysiology of Down syndrome.
Background/Objective The aim of the study was to examine the factor structure and psychometric properties of the Spanish version of the Mini-Mental Adjustment to Cancer Scale (Mini-MAC) in a large sample of patients with non-metastatic, resected cancer. Methods Prospective, observational, multicenter study for which 914 patients were recruited from 15 Spanish hospitals. Exploratory and confirmatory factor analyses, validity and reliability analyses were conducted. Results Factor-analytic results indicated a 4-factor structure of the Spanish version of the Mini-MAC. Three subscales have psychometric properties similar to those of Helplessness, Anxious preoccupation, and Cognitive avoidance of the original the Mini-MAC. The Fighting spirit and the Fatalism subscales were combined on the Positive attitude scale. The four factor-derived scale scores exhibited acceptable accuracy for individual measurement purposes, as well as stability over time in test-retest assessments at 6 months. Validity assessments found meaningful relations between the derived scale scores, and Brief Symptom Inventory depression and anxiety scores and Functional Assessment of Chronic Illness Therapy spiritual well-being scores. Conclusions The Spanish version of the Mini-MAC provides reliable and valid measures for patients with non-metastatic, resected cancer, and results corroborate the instrument’s cross-cultural validity.
Background/objectiveThe impact a cancer diagnosis and its treatment are affected by psychosocial factors and how these factors interrelate among themselves. The objective of this study was to analyze the relationship between optimism and social support in spiritual wellbeing in cancer patients initiating chemotherapy. MethodsA cross-sectional, multi-center (15 sites), prospective study was conducted with 912 cancer patients who had undergone curative surgery for a stage I-III cancer and were to receive adjuvant chemotherapy. They completed the Functional Assessment of Chronic Illness-Spiritual Well-being Scale (FACIT-Sp), Life Orientation Test-Revised (LOT-R), and the Multidimensional Scale of Perceived Social Support (MSPSS).
Quality of life (QoL) is a complex, ordinal endpoint with multiple conditioning factors. A predictive model of QoL after adjuvant chemotherapy can support decision making or the communication of information about the range of treatment options available. Patients with localized breast cancer (n = 219) were prospectively recruited at 17 centers. Participants completed the EORTC QLQ-C30 questionnaire. The primary aim was to predict health status upon completion of adjuvant chemotherapy adjusted for multiple covariates. We developed a Bayesian model with six covariates (chemotherapy regimen, TNM stage, axillary lymph node dissection, perceived risk of recurrence, age, type of surgery, and baseline EORTC scores). This model allows both prediction and causal inference. The patients with mastectomy reported a discrete decline on all QoL scores. The effect of surgery depended on the interaction with age. Women with ages on either end of the range displayed worse scores, especially with mastectomy. The perceived risk of recurrence had a striking effect on health status. In conclusion, we have developed a predictive model of health status in patients with early breast cancer based on the individual’s profile.
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