Causal hierarchy within the thalamo-cortical network in spike and wave discharges

Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al

Doubling time of circulating cea and its relation to survival of patients with recurrent colorectal cancer.

In a retrospective study the postoperative time courses of CEA in colorectal cancer patients with recurrent disease were analysed. In 87/114 cases with increasing concentrations of circulating CEA under close follow-up a linear relationship between log CEA and time could be established during disease recurrence. The individual doubling times of the serum CEA concentration in the log CEA period were calculated and found to cover distinct ranges dependent on the diagnosis of disease recurrence. The CEA doubling times concomitant with local recurrence or second primary carcinomas ranged from 142 to 868 days, visceral metastasis other than liver metastasis from 47 to 231 days and liver metastasis from 10 to 102 days. Patients with bone metastases exhibited CEA doubling times of 54-60 days and a patient with brain metastasis had a CEA doubling time of 598 days. The CEA doubling times of patients with liver metastasis and no further treatment, correlated well with the time of survival after the initial CEA increase of the log CEA phase (r = 0.870, n = 33). The mean survival expressed in multiples of the individual CEA doubling times was 7.0 +/- 1.8. Patients with liver metastasis who underwent various treatments of recurrent disease had a distinctly longer mean survival of 17.4 +/- 9.4 CEA doubling times (P less than 0.001). CEA doubling times can be used as a potential method to assess the efficacy of various treatments

When a photograph can be heard: Vision activates the auditory cortex within 110 ms

As the makers of silent movies knew well, it is not necessary to provide an actual auditory stimulus to activate the sensation of sounds typically associated with what we are viewing. Thus, you could almost hear the neigh of Rodolfo Valentino's horse, even though the film was mute. Evidence is provided that the mere sight of a photograph associated with a sound can activate the associative auditory cortex. High-density ERPs were recorded in 15 participants while they viewed hundreds of perceptually matched images that were associated (or not) with a given sound. Sound stimuli were discriminated from non-sound stimuli as early as 110 ms. SwLORETA reconstructions showed common activation of ventral stream areas for both types of stimuli and of the associative temporal cortex, at the earliest stage, only for sound stimuli. The primary auditory cortex (BA41) was also activated by sound images after ∼ 200 ms

The influence of age on the female/male ratio of treated incidence rates in depression

BACKGROUND: Poor data exist on the influence of psychosocial variables on the female/male ratio of depression because of the small number of cases and the resulting limited numbers of variables available for investigation. For this investigation a large number of first admitted depressed patients (N = 2599) was available which offered the unique opportunity to calculate age specific sex ratios for different marital and employment status categories. METHODS: Age and sex specific population based depression rates were calculated for first ever admissions for single year intervals. Moving averages with interpolated corrections for marginal values in the age distribution were employed. RESULTS: For the total group the female/male ratio of depression showed an inverted U-shape over the life-cycle. This pattern was influenced by the group of married persons, which showed a sex-ratio of 3:1 between the age of 30–50, but ratios of around 1:1 at younger and older ages. For not married persons the female/male ratio was already around 2:1 at the age of 18 and rose to 2.5:1 in mid-life and declined to 1 at around 55. The almost parallel decline of depression rates in employed men and women resulted in a female/male ratio of about 2:1 from age 18 to age 50 and became 1 after the age of 60. The female/male ratio among the not employed was about 1, in mid-life it became negative. CONCLUSIONS: Our analyses show that the gender-gap in first admitted depressed patients is age dependent and that psychosocial factors modify the sex ratio

Brain function assessment in different conscious states

Background: The study of brain functioning is a major challenge in neuroscience fields as human brain has a dynamic and ever changing information processing. Case is worsened with conditions where brain undergoes major changes in so-called different conscious states. Even though the exact definition of consciousness is a hard one, there are certain conditions where the descriptions have reached a consensus. The sleep and the anesthesia are different conditions which are separable from each other and also from wakefulness. The aim of our group has been to tackle the issue of brain functioning with setting up similar research conditions for these three conscious states.Methods: In order to achieve this goal we have designed an auditory stimulation battery with changing conditions to be recorded during a 40 channel EEG polygraph (Nuamps) session. The stimuli (modified mismatch, auditory evoked etc.) have been administered both in the operation room and the sleep lab via Embedded Interactive Stimulus Unit which was developed in our lab. The overall study has provided some results for three domains of consciousness. In order to be able to monitor the changes we have incorporated Bispectral Index Monitoring to both sleep and anesthesia conditions.Results: The first stage results have provided a basic understanding in these altered states such that auditory stimuli have been successfully processed in both light and deep sleep stages. The anesthesia provides a sudden change in brain responsiveness; therefore a dosage dependent anesthetic administration has proved to be useful. The auditory processing was exemplified targeting N1 wave, with a thorough analysis from spectrogram to sLORETA. The frequency components were observed to be shifting throughout the stages. The propofol administration and the deeper sleep stages both resulted in the decreasing of N1 component. The sLORETA revealed similar activity at BA7 in sleep (BIS 70) and target propofol concentration of 1.2 μg/mL.Conclusions: The current study utilized similar stimulation and recording system and incorporated BIS dependent values to validate a common approach to sleep and anesthesia. Accordingly the brain has a complex behavior pattern, dynamically changing its responsiveness in accordance with stimulations and states. © 2010 Ozgoren et al; licensee BioMed Central Ltd