Stimulation in the Dorsolateral Prefrontal Cortex Changes Subjective Evaluation of Percepts

<div><p>Nelson and Narens have proposed a metacognition model that dissociates the objective processing of information (object-level) and the subjective evaluation of the performance (i.e., the metalevel). Neurophysiological evidence also indicates that the prefrontal cortices (PFC) are the brain areas which perform the metalevel function <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106943#pone.0106943-FernandezDuque1" target="_blank">[1]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106943#pone.0106943-Stuss1" target="_blank">[3]</a>. A corresponding neural mechanism of Nelson and Narens’s model, called dynamic filtering theory <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106943#pone.0106943-Shimamura1" target="_blank">[4]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106943#pone.0106943-Shimamura2" target="_blank">[5]</a>, indicates that object-level processing is distributed in the posterior cortices and regulated by the prefrontal cortices with a filtering or gating mechanism to select appropriate signals and suppress inappropriate signals and noise. Based on this model, a hypothesis can be developed that, in the case of uncertainty or overloading of object-level processing, the prefrontal cortices will become more active in order to modulate signals and noise. This hypothesis is supported by a recent fMRI study <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106943#pone.0106943-Chiang1" target="_blank">[6]</a> showing that the PFC (Brodmann area 9, BA9) was activated when subjects were overloaded in a bimodal attentional task, compared to a unimodal task. Here, we report a study showing that applying repetitive transmagnetic stimulation (rTMS) over the BA9 in order to interfere with its functional activity resulted in significant increas in guessed responses, compared to three other control conditions (i.e., no-TMS, sham TMS on BA9, and rTMS on Cz). The results are compatible with the dynamic filtering theory and suggest that a malfunction of the PFC would weaken the quality of meta-cognitive percepts and increase the number of guessed responses.</p></div

Response categories.

<p>Responses were categorized according to the subjects’ assessment of their confidence in their ability to bind features and correctness in binding. Confident responses were represented as the combination of Cell A and Cell C, while guessing responses were represented as the combination of Cell B and Cell D.</p><p>Response categories.</p

The number of confident and guessed responses in the rTMS experiment, grouped by stimulation site.

<p>The total number of trials for each subject was 32. The number of guessed trials significantly increased only while rTMS was over BA9 and not for the sham TMS or Cz stimulation, compared with the no-TMS condition (the non-linear mixed effect model was adopted, t₄ = 11.31, p = 0.0003). Cz is the top of the head, according to the 10–20 EEG system.</p

The distribution of accuracy in the rTMS experiment, grouped both by the factor of confident or guessed responses and by stimulation site.

<p>The error bar of each column indicates the standard error of the data. The accuracies of the guessed trials among the four stimulation sites were similar, all at the chance level (the non-linear mixed effect model was adopted, rTMS on BA9 versus no-TMS, t₄ = 1.64, p = 0.1768; sham TMS on BA9 versus no-TMS, t₄ = 0.57, p = 0.5980; rTMS on Cz versus no-TMS, t₄ = 0.67, p = 0.5378).</p

The aldehyde dehydrogenase 2 polymorphisms on neuropsychological performance in bipolar II disorder with or without comorbid anxiety disorder

<div><p>Anxiety disorders (ADs), the most common comorbid illnesses with bipolar disorder (BP) has been reported to associate with dopamine system. Dopamine, metabolized to 3,4-dihydroxyphenylacetic acid (DOPAC) by aldehyde dehydrogenase 2 (ALDH2), and the distribution of the <i>ALDH2*1/*1</i>, and <i>ALDH2*1/*2+ALDH*2/*2</i> alleles in the Han Chinese general population is relatively equal. The association between dopamine metabolic enzymes and cognitive performance in patients with bipolar II disorder (BP-II) comorbid with AD is unclear. This study proposed to explore the role of <i>ALDH2</i> polymorphisms on neuropsychological performance between BP-II comorbid with or without AD. One hundred ninety-seven BP-II patients with and without a comorbid AD were recruited and compared with 130 healthy controls (HCs). A polymerase chain reaction and a restriction fragment length polymorphism analysis were used to determine genotypes for <i>ALDH2</i>, and study participants underwent neuropsychological tests. An interaction between AD comorbidity and the <i>ALDH2</i> polymorphisms was found in different domain of cognitive dysfunction in the BP-II patients. The <i>ALDH2</i> polymorphisms might have different effects on the neuropsychological performance of BP-II patients with and without comorbid AD.</p></div

Neuropsychological performance in memory between patient groups and healthy controls.

<p>Neuropsychological performance in memory between patient groups and healthy controls.</p

Demographic data comparisons between patient groups and healthy controls.

<p>Demographic data comparisons between patient groups and healthy controls.</p

Neuropsychological performance in attention and executive function between patient groups and healthy controls.

<p>Neuropsychological performance in attention and executive function between patient groups and healthy controls.</p

The <i>SLC6A3</i> gene possibly affects susceptibility to late-onset alcohol dependence but not specific personality traits in a Han Chinese population

<div><p>Dopaminergic dysfunction has an important role in the pathoetiology of alcohol dependence (AD). The purpose of this study was to determine whether the solute carrier family 6 member 3 (<i>SLC6A3</i>) gene (also known as the dopamine transporter <i>DAT</i> gene) was associated with AD, and whether variants in the <i>SLC6A3</i> locus were associated with specific personality traits in patients with AD. Sixteen polymorphisms in <i>SLC6A3</i> were analyzed using 637 patients with AD and 523 healthy controls. To reduce clinical heterogeneity, patients were classified into two subgroups: early-onset AD (EOAD) and late-onset AD (LOAD). The Tridimensional Personality Questionnaire was used to assess the personality traits novelty seeking (NS) and harm avoidance (HA) in the patients with AD. Using allele frequency and genotype distribution comparisons and logistic regression analysis, we found evidence of association between rs6350 and AD (<i>P</i> < 0.05). Following subgroup analysis, we confirmed evidence of an association in patients with LOAD (<i>P</i> = 0.003), but not in patients with EOAD. Heterozygous carriers of the A allele have a nearly 3 times greater risk to develop LOAD compared to individuals who do not have an A allele. Although we found that patients with AD had higher NS and HA scores compared to controls (<i>P</i> < 0.001), we did not find evidence of association between <i>SLC6A3</i> polymorphisms and either NS or HA in patients with AD using linear regression analysis. The findings from our study indicate that the <i>SLC6A3</i> gene may have a role in susceptibility to late-onset AD in the Han Chinese population.</p></div

Summaries of multifactor dimension reduction gene-gene interaction results in sample I.

<p>Training Bal. Acc.: training-balanced accuracy</p><p>Testing Bal. Acc.: testing-balanced accuracy</p><p>SNP: single-nucleotide polymorphism</p><p>Summaries of multifactor dimension reduction gene-gene interaction results in sample I.</p