Finasteride as a model for personalized medicine

The side effects of Finasteride are currently a subject of controversy. Some studies report minor or acceptable adverse effects, which decrease after a variable period of time so that they do not necessitate terminating Finasteride administration. However, several clinical and neuro-endocrine studies show that some adverse effects persist indefinitely in the form of post-Finasteride syndrome, even after the drug cessation. This paper presents a possible explanation for these inconsistent findings. First, the study design of either informing or not informing patients prior therapy about possible adverse effects can influence the incidence and magnitude of reported adverse effects. Second, structural and information dichotomies of the brain generate four distinct neuronal networks, which are activated through specific cerebral neuromodulators and that are able to support four distinct minds within an individual body. As a conclusion, the “mind psychophysiology” and the corresponding mental impairments differ across individuals, such that not only the prediction of adverse effects should be addressed from a more individualized medical perspective, but also the therapeutic strategies could be tailored to the four distinct mental profiles described. It is a personalized approach that would be applicable to several interrelated domains of neuroscience, like psychology, psychiatry and sexuality. Finally, this perspective may represent a starting point for a more individualized understanding of mental events, perhaps even a step forward in the understanding of the mind-body problem

Brain Dynamics across levels of Organization

After presenting evidence that the electrical activity recorded from the brain surface can reflect metastable state transitions of neuronal configurations at the mesoscopic level, I will suggest that their patterns may correspond to the distinctive spatio-temporal activity in the Dynamic Core (DC) and the Global Neuronal Workspace (GNW), respectively, in the models of the Edelman group on the one hand, and of Dehaene-Changeux, on the other. In both cases, the recursively reentrant activity flow in intra-cortical and cortical-subcortical neuron loops plays an essential and distinct role. Reasons will be given for viewing the temporal characteristics of this activity flow as signature of Self-Organized Criticality (SOC), notably in reference to the dynamics of neuronal avalanches. This point of view enables the use of statistical Physics approaches for exploring phase transitions, scaling and universality properties of DC and GNW, with relevance to the macroscopic electrical activity in EEG and EMG

Cognitive performance is related to central sensitization and health-related quality of life in patients with chronic whiplash-associated disorders and fibromyalgia

Background: A growing body of research has demonstrated that impaired central pain modulation or central sensitization (CS) is a crucial mechanism for the development of persistent pain in chronic whiplash-associated disorders (WAD) and fibromyalgia (FM) patients. Furthermore, there is increasing evidence for cognitive dysfunctions among these patients. In addition, chronic WAD and FM patients often report problems with health-related quality of life (QoL). Yet, there is limited research concerning the interrelations between cognitive performance, indices of CS, and health-related QoL in these patients. Objectives: (1) Examining the presence of cognitive impairment, CS, and limitations on health-related QoL in patients with chronic WAD and FM compared to healthy controls. (2) Examining interrelations between performance-based cognitive functioning, CS, and self-reported health-related QoL in these 3 study groups. Study Design: A case-control study was conducted. Setting: The present study took place at the University Hospital Brussels, the University of Brussels, and the University of Antwerp. Methods: Fifty-nine patients (16 chronic WAD patients, 21 FM patients, and 22 pain-free volunteers) filled out the Short Form 36 item Health Survey (SF-36), a self-reported psychosocial questionnaire, to assess health-related QoL. Next, they were subjected to various pain measurements (pressure hyperalgesia, deep-tissue hyperalgesia, temporal summation [TS], and conditioned pain modulation [CPM]). Finally, participants completed a battery of performance-based cognitive tests (Stroop task, psychomotor vigilance task [PVT], and operation span task [OSPAN]). Results: Significant cognitive impairment, bottom-up sensitization, and decreased health-related QoL were demonstrated in patients with chronic WAD and FM compared to healthy controls (P < 0.017). CPM was comparable between the 3 groups. Cognitive performance was significantly related to central pain modulation (deep-tissue hyperalgesia, TS, CPM) as well as to self-reported health-related QoL (P < 0.05). Decreased cognitive performance was related to deficient central pain modulation in healthy controls. Further, significant correlations between decreased cognitive performance and reduced health-related QoL were revealed among all study groups. Additionally, FM patients showed correlations between cognitive impairment and increased health-related QoL. Remarkably, impaired selective attention and working memory were related to less TS, whereas impaired sustained attention was correlated with dysfunctional CPM in FM patients. Limitations: Based on the current cross-sectional study no firm conclusions can be drawn on the causality of the relations. Conclusion: In conclusion, this paper has demonstrated significant cognitive deficits, signs of CS, and reduced health-related QoL in chronic WAD and FM patients compared to healthy individuals. Significant relations between cognitive performance and CS as well as health-related QoL were demonstrated. These results provide preliminary evidence for the clinical importance of objectively measured cognitive deficits in patients with chronic WAD and FM

Indices of Coherence of EEG Rhythms in the Course of Cognitive Activity as Markers of Creative Thinking: Gender Specificity

According to the results of psychological testing, persons aged 18 to 21 years were divided into four groups, women and men with low and high productivity of divergent (creative, nonroutine) thinking (n = = 18 to 23). Results of EEG recording (19 leads) were used for calculation of the coherence coefficients for oscillations of the delta, theta, alpha1, alpha2, alpha3, beta, and gamma frequencies in lead pairs and estimation of integral indices of coherence within the anterior and posterior cortical regions and between these zones (interaction coefficients, IC1-IC3, respectively). EEG was recorded in the resting state and in the course of resolving convergent- and divergent-type cognitive test tasks. It was found that, during the performance of tests of both types, men with a higher productivity of divergent thinking demonstrated significantly higher values of IC1 (that characterizes the coherence in associative linkages within the anterior cortex) for oscillations of all EEG frequency ranges compared with the respective estimates for “low-creative” men. Similar increments were typical of the IC2 values for low- and mid- frequency EEG rhythms (delta, theta, and alpha). At the same time, values of the “interregional” IC3 for theta, beta, and gamma activity in “high-creativity” men were significantly lower. In women of both groups (low and high creativity), such specificity of the IC1-IC3 patterns was practically not observed, i.e., the respective aspect demonstrated clear gender specificity. The sex of the subjects and type of the performed cognitive tests could not be considered factors significantly affecting the calculated absolute IC values. The observed specificities of integral coherence indices are probably associated with different strategies of the performance of cognitive tasks in men and women. Our findings allow us to believe that the above interrelations between integrated coherence indices can be used as EEG markers of high productivity of divergent thinking in men. The more flexible strategies of thinking in women are probably related to more variable neurophysiological cortical mechanisms (compared with those in men), and this type of organization is not clearly reflected in the pattern of intracortical interactions estimated by coherence indices

Molecular implications of prolonged aggression experience: Th, Dat1, Snca and Bdnf gene expression in the ventral tegmental area of the victorious male mice

Th, Dat1, Snca and Bdnf were the genes whose mRNA levels in the ventral tegmental area of the midbrain were measured in male mice that were victorious in 20 daily agonistic interactions and in a group of such victorious mice that had later not been allowed to fight for 14 days. This experiment demonstrated increased Th, Dat1 and Snca but not Bdnf mRNA levels in the former group as compared to the controls. In the latter group, the expression of the Th and Dat1 genes was still enhanced, while the level of Snca mRNA did not differ from that in the controls. These findings suggest that positive fighting experience enhances the expression of the genes concerned with dopaminergic systems and this enhanced expression is preserved for a long time afterwards. Significant positive correlations were found between the level of aggression and Th and Snca mRNA levels in the winners

Consciousness, cognition, and the hierarchy of context: extending the global neuronal workspace model

We adapt an information theory analysis of interacting cognitive biological and social modules to the problem of the global neuronal workspace, the new standard neuroscience paradigm for consciousness. Tunable punctuation emerges in a natural way, suggesting the possibility of fitting appropriate phase transition power law, and away from transition, generalized Onsager relation expressions, to observational data on conscious reaction. The development can be extended in a straightforward manner to include psychosocial stress, culture, or other cognitive modules which constitute a structured, embedding hierarchy of contextual constraints acting at a slower rate than neuronal function itself. This produces a 'biopsychosociocultural' model of individual consciousness that, while otherwise quite close to the standard treatment, meets compelling philosophical and other objections to brain-only descriptions

Neuronal avalanches differ from wakefulness to deep sleep - evidence from intracranial depth recordings in humans

Neuronal activity differs between wakefulness and sleep states. In contrast, an attractor state, called self-organized critical (SOC), was proposed to govern brain dynamics because it allows for optimal information coding. But is the human brain SOC for each vigilance state despite the variations in neuronal dynamics? We characterized neuronal avalanches – spatiotemporal waves of enhanced activity - from dense intracranial depth recordings in humans. We showed that avalanche distributions closely follow a power law – the hallmark feature of SOC - for each vigilance state. However, avalanches clearly differ with vigilance states: slow wave sleep (SWS) shows large avalanches, wakefulness intermediate, and rapid eye movement (REM) sleep small ones. Our SOC model, together with the data, suggested first that the differences are mediated by global but tiny changes in synaptic strength, and second, that the changes with vigilance states reflect small deviations from criticality to the subcritical regime, implying that the human brain does not operate at criticality proper but close to SOC. Independent of criticality, the analysis confirms that SWS shows increased correlations between cortical areas, and reveals that REM sleep shows more fragmented cortical dynamics

Olig2/Plp-positive progenitor cells give rise to Bergmann glia in the cerebellum.

NG2 (nerve/glial antigen2)-expressing cells represent the largest population of postnatal progenitors in the central nervous system and have been classified as oligodendroglial progenitor cells, but the fate and function of these cells remain incompletely characterized. Previous studies have focused on characterizing these progenitors in the postnatal and adult subventricular zone and on analyzing the cellular and physiological properties of these cells in white and gray matter regions in the forebrain. In the present study, we examine the types of neural progeny generated by NG2 progenitors in the cerebellum by employing genetic fate mapping techniques using inducible Cre-Lox systems in vivo with two different mouse lines, the Plp-Cre-ER(T2)/Rosa26-EYFP and Olig2-Cre-ER(T2)/Rosa26-EYFP double-transgenic mice. Our data indicate that Olig2/Plp-positive NG2 cells display multipotential properties, primarily give rise to oligodendroglia but, surprisingly, also generate Bergmann glia, which are specialized glial cells in the cerebellum. The NG2+ cells also give rise to astrocytes, but not neurons. In addition, we show that glutamate signaling is involved in distinct NG2+ cell-fate/differentiation pathways and plays a role in the normal development of Bergmann glia. We also show an increase of cerebellar oligodendroglial lineage cells in response to hypoxic-ischemic injury, but the ability of NG2+ cells to give rise to Bergmann glia and astrocytes remains unchanged. Overall, our study reveals a novel Bergmann glia fate of Olig2/Plp-positive NG2 progenitors, demonstrates the differentiation of these progenitors into various functional glial cell types, and provides significant insights into the fate and function of Olig2/Plp-positive progenitor cells in health and disease