EEG Phase Synchronization in Persons With Depression Subjected to Transcranial Magnetic Stimulation

Aim: The main objective of this work was to study the impact of repetitive Transcranial Magnetic Stimulation (rTMS) treatment on brain activity in 8 patients with major depressive disorder (MDD) and 10 patients with bipolar disorder (BP). Changes due to rTMS stimulation of the left dorsolateral prefrontal cortex (DLPFC) were investigated considering separately responders and non-responders to therapy in each of both groups. The aim of the research is to determine whether non-responders differ from responders suffered from both diseases, as well as if any change occurred due to rTMS across consecutive rTMS sessions.Methods: The graph-theory-based connectivity analysis of non-linearity measure of phase interdependencies—Phase Locking Value (PLV)—was examined from EEG data. The approximately 15-min EEG recordings from each of participants were recorded before and after 1st, 10th, and 20th session, respectively. PLV calculated from data was analyzed using principal graph theory indices (strength and degree) within five physiological frequency bands and in individual channels separately. The impact of rTMS on the EEG connectivity in every group of patients evaluated by PLV was assessed.Results: Each of four groups reacted differently to rTMS treatment. The strength and degree of PLV increased in gamma band in both groups of responders. Moreover, an increase of indices in beta band for BP-responders was observed. While, in MDD-non-responders the indices decreased in gamma band and increased in beta band. Moreover, the index strength was lower in alpha band for BP- non-responders. The rTMS stimulation caused topographically specific changes, i.e., the increase of the activity in the left DLPFC as well as in other brain regions such as right parieto-occipital areas.Conclusions: The analysis of PLV allowed for evaluation of the rTMS impact on the EEG activity in each group of patients. The changes of PLV under stimulation might be a good indicator of response to depression treatment permitting to improve the effectiveness of therapy

Complexity Analysis of EEG Data in Persons With Depression Subjected to Transcranial Magnetic Stimulation

Aim: The aim of this work was to study the neurophysiological effect of repetitive transcranial magnetic stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) in 8 patients with major depression disorder (MDD) and 10 patients with bipolar disorder (BP), considering separately responders and non-responders to rTMS therapy in each of both groups.Methods: The Higuchi’s Fractal Dimension (FD) was analyzed from 64-channels EEG signals in five physiological frequency bands and every channel separately. Changes of FD were analyzed before and after 1st, 10th, and 20th session of rTMS.Results: Some differences in response to the rTMS therapy was found across individual groups. In MDD responders, FD decreased in all bands after longer stimulation (20th session). Whereas, in BP non-responders, FD decreased after 1st session in all bands as well as after 10th session in lower frequencies (delta and theta). In MDD non-responders and BP responders FD increased at the beginning of the therapy (1st and 10th session, respectively), but the final FD value did not changed in comparison to the initial FD value, except the FD decrease for theta band in BP responders. Comparison between groups showed a higher FD in MDD responders than in MDD non-responders in every band before as well as after stimulation. In contrast to MDD patients, FD was lower in BP responders than in BP non-responders in higher frequency bands (alpha, beta, and gamma) in both conditions as well as in lower frequency bands (delta and theta) after stimulation. Comparing both groups of responders, FD was lower in MDD than in BP in every band, except alpha. In case of non-responders, FD was higher in BP than in MDD in all bands in both conditions.Conclusion: The results showed that FD may be useful marker for evaluation of the rTMS effectiveness and the therapy progress as well as for group differentiation between MDD and BP or between responders and non-responders. The changes of FD under the influence of rTMS allow to unambiguously conclude whether the effect of stimulation is positive or negative as well as allow to evaluate an optimal time of rTMS

Questioning surveillance

The aim of this article is to make suggestions that could empower different socio-political groups to question surveillance. It does so by formulating sets of questions that different stakeholders can ask of themselves, of the private sector, and of government, including intelligence agencies. It is divided into three main parts. The first part provides some background on resilience in surveillance societies. It defines the terms and identifies features of resilience and today’s surveillance society. The second part lays out a set of questions addressed to each of the stakeholder groups. The questions are intended to promote consideration of a proposed or existing surveillance system, technology, practice or other initiative in terms of the necessity and proportionality of the system, and of whether stakeholders are being consulted. The third part offers a list of measures that can be taken to increase resilience in a surveillance society, to restrict the scope of surveillance systems to what can be legitimately justified, and to minimise the impacts of surveillance systems on the individual, groups and society

Association between Age and the 7 Repeat Allele of the Dopamine D4 Receptor Gene

Longevity is in part (25%) inherited, and genetic studies aim to uncover allelic variants that play an important role in prolonging life span. Results to date confirm only a few gene variants associated with longevity, while others show inconsistent results. However, GWAS studies concentrate on single nucleotide polymorphisms, and there are only a handful of studies investigating variable number of tandem repeat variations related to longevity. Recently, Grady and colleagues (2013) reported a remarkable (66%) accumulation of those carrying the 7 repeat allele of the dopamine D4 receptor gene in a large population of 90-109 years old Californian centenarians, as compared to an ancestry-matched young population. In the present study we demonstrate the same association using continuous age groups in an 18-97 years old Caucasian sample (N = 1801, p = 0.007). We found a continuous pattern of increase from 18-75, however frequency of allele 7 carriers decreased in our oldest age groups. Possible role of gene-environment interaction effects driven by historical events are discussed. In accordance with previous findings, we observed association preferentially in females (p = 0.003). Our results underlie the importance of investigating non-disease related genetic variants as inherited components of longevity, and confirm, that the 7-repeat allele of the dopamine D4 receptor gene is a longevity enabling genetic factor, accumulating in the elderly female population

What Are Reasons for the Large Gender Differences in the Lethality of Suicidal Acts? An Epidemiological Analysis in Four European Countries

BackgroundIn Europe, men have lower rates of attempted suicide compared to women and at the same time a higher rate of completed suicides, indicating major gender differences in lethality of suicidal behaviour. The aim of this study was to analyse the extent to which these gender differences in lethality can be explained by factors such as choice of more lethal methods or lethality differences within the same suicide method or age. In addition, we explored gender differences in the intentionality of suicide attempts.Methods and FindingsMethods. Design: Epidemiological study using a combination of self-report and official data. Setting: Mental health care services in four European countries: Germany, Hungary, Ireland, and Portugal. Data basis: Completed suicides derived from official statistics for each country (767 acts, 74.4% male) and assessed suicide attempts excluding habitual intentional self-harm (8,175 acts, 43.2% male).Main Outcome Measures and Data Analysis. We collected data on suicidal acts in eight regions of four European countries participating in the EU-funded "OSPI-Europe"-project (www.ospi-europe.com). We calculated method-specific lethality using the number of completed suicides per method * 100 /(number of completed suicides per method + number of attempted suicides per method). We tested gender differences in the distribution of suicidal acts for significance by using the chi(2)-test for two-by-two tables. We assessed the effect sizes with phi coefficients (phi). We identified predictors of lethality with a binary logistic regression analysis. Poisson regression analysis examined the contribution of choice of methods and method-specific lethality to gender differences in the lethality of suicidal acts.Findings Main ResultsSuicidal acts (fatal and non-fatal) were 3.4 times more lethal in men than in women (lethality 13.91% (regarding 4106 suicidal acts) versus 4.05% (regarding 4836 suicidal acts)), the difference being significant for the methods hanging, jumping, moving objects, sharp objects and poisoning by substances other than drugs. Median age at time of suicidal behaviour (35-44 years) did not differ between males and females. The overall gender difference in lethality of suicidal behaviour was explained by males choosing more lethal suicide methods (odds ratio (OR) = 2.03; 95% CI = 1.65 to 2.50; p &lt;0.000001) and additionally, but to a lesser degree, by a higher lethality of suicidal acts for males even within the same method (OR = 1.64; 95% CI = 1.32 to 2.02; p = 0.000005). Results of a regression analysis revealed neither age nor country differences were significant predictors for gender differences in the lethality of suicidal acts. The proportion of serious suicide attempts among all non-fatal suicidal acts with known intentionality (NFSAi) was significantly higher in men (57.1%; 1,207 of 2,115 NFSAi) than in women (48.6%; 1,508 of 3,100 NFSAi) (chi(2) = 35.74; p &lt;0.000001).Main limitations of the studyDue to restrictive data security regulations to ensure anonymity in Ireland, specific ages could not be provided because of the relatively low absolute numbers of suicide in the Irish intervention and control region. Therefore, analyses of the interaction between gender and age could only be conducted for three of the four countries. Attempted suicides were assessed for patients presenting to emergency departments or treated in hospitals. An unknown rate of attempted suicides remained undetected. This may have caused an overestimation of the lethality of certain methods. Moreover, the detection of attempted suicides and the registration of completed suicides might have differed across the four countries. Some suicides might be hidden and misclassified as undetermined deaths.ConclusionsMen more often used highly lethal methods in suicidal behaviour, but there was also a higher method-specific lethality which together explained the large gender differences in the lethality of suicidal acts. Gender differences in the lethality of suicidal acts were fairly consistent across all four European countries examined. Males and females did not differ in age at time of suicidal behaviour. Suicide attempts by males were rated as being more serious independent of the method used, with the exceptions of attempted hanging, suggesting gender differences in intentionality associated with suicidal behaviour. These findings contribute to understanding of the spectrum of reasons for gender differences in the lethality of suicidal behaviour and should inform the development of gender specific strategies for suicide prevention.</p

Heterogeneity of circulating tumour cell-associated genomic gains in breast cancer and its association with the host immune response.

Tumor cells that preferentially enter circulation include the precursors of metastatic cancer. Previously, we characterized circulating tumor cells (CTC) from patients with breast cancer and identified a signature of genomic regions with recurrent copy-number gains. Through FISH, we now show that these CTC-associated regions are detected within the matched untreated primary tumors of these patients (21% to 69%, median 55.5%, n = 19). Furthermore, they are more prevalent in the metastases of patients who died from breast cancer after multiple rounds of treatment (70% to 100%, median 93%, samples n = 41). Diversity indices revealed that higher spatial heterogeneity for these regions within primary tumors is associated with increased dissemination and metastasis. An identified subclone with multiple regions gained (MRG clone) was enriched in a posttreatment primary breast carcinoma as well as multiple metastatic tumors and local breast recurrences obtained at autopsy, indicative of a distinct early subclone with the capability to resist multiple lines of treatment and eventually cause death. In addition, multiplex immunofluorescence revealed that tumor heterogeneity is significantly associated with the degree of infiltration of B lymphocytes in triple-negative breast cancer, a subtype with a large immune component. Collectively, these data reveal the functional potential of genetic subclones that comprise heterogeneous primary breast carcinomas and are selected for in CTCs and posttreatment breast cancer metastases. In addition, they uncover a relationship between tumor heterogeneity and host immune response in the tumor microenvironment. SIGNIFICANCE: As breast cancers progress, they become more heterogeneous for multiple regions amplified in circulating tumor cells, and intratumoral spatial heterogeneity is associated with the immune landscape