Functional parcellation of the inferior frontal and midcingulate cortices in a flanker‐stop‐change paradigm

Conflict monitoring and motor inhibition are engaged in the performance of complex tasks. The midcingulate cortex (MCC) has been suggested to detect conflicts, whereas the right inferior frontal cortex (IFC) seems to be of relevance for the inhibition process. The current experiment investigates the neural underpinnings of their interplay via a modified flanker paradigm. Conflict was manipulated by the congruency of flanking stimuli relative to a target (congruent vs. incongruent) and motor inhibition by a within‐trial response change of the initiated response (keep response vs. stop‐change). We used event‐related functional magnetic resonance imaging, decomposition with high model order ICA, and single trial analysis to derive a functional parcellation of the whole‐brain data. Results demonstrate the segmentation of the MCC into anterior and posterior subregions, and of the IFC into the pars opercularis, pars triangularis, and pars orbitalis. The pars opercularis and pars triangularis of the right IFC constituted the foundation of inhibition‐related networks. With high conflict on incongruent trials, activity in the posterior MCC network, as well as in one right IFC network was observed. Stop‐change trials modulated both the MCC as well as networks covering extended parts of the IFC. Whereas conflict processing and inhibition most often are studied separately, this study provides a synopsis of functionally coupled brain regions acting in concert to enable an optimal performance in situations involving interference and inhibition. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

The effects of background noise on dichotic listening to consonant-vowel syllables: An fMRI study

The present fMRI study attempts to identify brain areas that may underlie the effect of different background noises on functional brain asymmetry in a dichotic listening task. Previous studies have shown that the prominent right ear advantage in dichotic listening to consonant-vowel syllables is affected by background noise. To explore the underlying neuronal processes, haemodynamic brain responses using fMRI were recorded while participants performed the dichotic listening task in two different noisy backgrounds (conversational “babble” and traffic noise). The behavioural results showed a reduction of the right ear advantage in the background noise conditions, especially in the traffic noise condition. The behavioural results are discussed in terms of alertness-attentional mechanisms. The effects of background noise on brain activation involved significant activations in a speech-processing network. Specifically the changes in activations in the peri-Sylvian region of the superior temporal gyrus and in the temporo-parietal junction part in the left hemisphere, as well as in the superior temporal gyrus/sulcus area in the right hemisphere may mirror the effects of noise on behavioural performance. The effects of noise on brain activation are discussed with regard to pre-activation mechanisms.     

CD11c‐positive cells from brain,spleen, lung,and liver exhibit site‐specific immune phenotypes and plastically adapt to new environments

The brain's immune privilege has been also attributed to the lack of dendritic cells (DC) within its parenchyma and the adjacent meninges, an assumption, which implies maintenance of antigens rather than their presentation in lymphoid organs. Using mice transcribing the green fluorescent protein under the promoter of the DC marker CD11c (itgax), we identified a juxtavascular population of cells expressing this DC marker and demonstrated their origin from bone marrow and local microglia. We now phenotypically compared this population with CD11c/CD45 double‐positive cells from lung, liver, and spleen in healthy mice using seven‐color flow cytometry. We identified unique, site‐specific expression patterns of F4/80, CD80, CD86, CX3CR1, CCR2, FLT3, CD103, and MHC‐II. Furthermore, we observed the two known CD45‐positive populations (CD45^high and CD45^int) in the brain, whereas liver, lung, and spleen exhibited a homogeneous CD45^high population. CD11c‐positive microglia lacked MHC‐II expression and CD45^high/CD11c‐positive cells from the brain have a lower percentage of MHC‐II‐positive cells. To test whether phenotypical differences are fixed by origin or specifically develop due to environmental factors, we transplanted brain and spleen mononuclear cells on organotypic slice cultures from brain (OHSC) and spleen (OSSC). We demonstrate that adaption and ramification of MHC‐II‐positive splenocytes is paralleled by down‐regulation of MHC‐II, whereas brain‐derived mononuclear cells neither ramified nor up‐regulated MHC‐II in OSSCs. Thus, brain‐derived mononuclear cells maintain their MHC‐II‐negative phenotype within the environment of an immune organ. Intraparenchymal CD11c‐positive cells share immunophenotypical characteristics of DCs from other organs but remain unique for their low MHC‐II expression. GLIA 2015;63:611–625     

Risk factors for executive dysfunction after subthalamic nucleus stimulation in Parkinson's disease

A slight decline in cognitive functions and especially in executive functioning after deep brain stimulation (DBS) of the nucleus subthalamicus (STN) in patients with Parkinson's disease (PD) has been described. This study evaluated baseline parameters that contribute to a deterioration of cognitive functioning after DBS. We analyzed data from the neuropsychological protocol in a randomized controlled study comparing DBS with best medical treatment (BMT). Change scores were calculated for the cognitive domains “global cognitive functioning,” “memory,” “working memory,” “attention,” and “executive function.” These domain‐specific change scores were correlated with previously defined preoperative parameters. Compared with the BMT group (63 patients), the STN‐DBS group (60 patients) showed a significant decline only in the domain executive function 6 months after DBS, which was significantly correlated with age, levodopa‐equivalence dosage (LED) and axial subscore of the UPDRS in the off‐medication state at baseline. Multiple regression analysis showed that these three factors explained, however, only about 23% of the variance. Patients with higher age, higher baseline LED, and/or higher axial subscore of the UPDRS at baseline have an increased risk for worsening of executive function after STN‐DBS. High scores of these factors might reflect an advanced stage of disease progression. As these baseline factors explained the variance of the change score executive function only to a minor proportion, other factors including the surgical procedure, the exact placement of the electrode or postsurgical management might be more relevant for a decline in executive functioning after STN‐DBS. © 2010 Movement Disorder Society     

The facial expression of pain in patients with dementia

The facial expression of pain has emerged as an important pain indicator in demented patients, who have difficulties in providing self-report ratings. In a few clinical studies an increase of facial responses to pain was observed in demented patients compared to healthy controls. However, it had to be shown that this increase can be verified when using experimental methods, which also allows for testing whether the facial responses in demented patients are still typical for pain. We investigated facial responses in 42 demented patients and 54 aged-matched healthy controls to mechanically induced pain of various intensities. The face of the subject was videotaped during pressure stimulation and was later analysed using the Facial Action Coding System. Besides facial responses we also assessed self-report ratings. Comparable to previous findings, we found that facial responses to noxious stimulation were significantly increased in demented patients compared to healthy controls. This increase was mainly due to an increase of pain-indicative facial responses in demented patients. Moreover, facial responses were closely related to the intensity of stimulation, especially in demented patients. Regarding self-report ratings, we found no significant group differences; however, the capacity to provide these self-report ratings was diminished in demented patients. The preserved pain typicalness of facial responses to noxious stimulation suggests that pain is reflected as validly in the facial responses of demented patients as it is in healthy individuals. Therefore, the facial expression of pain has the potential to serve as an alternative pain assessment tool in demented patients, even in patients who are verbally compromised.     

Inclusion of CYP3A5 genotyping in a nonparametric population model improves dosing of tacrolimus early after transplantation

Following organ engraftment, initial dosing of tacrolimus is based on recipient weight and adjusted by measured C₀ concentrations. The bioavailability and elimination of tacrolimus are affected by the patients CYP3A5 genotype. Prospective data of the clinical advantage of knowing patient's CYP3A5 genotype prior to transplantation are lacking. A nonparametric population model was developed for tacrolimus in renal transplant recipients. Data from 99 patients were used for model development and validation. A three‐compartment model with first‐order absorption and lag time from the dosing compartment described the data well. Clearances and volumes of distribution were allometrically scaled to body size. The final model included fat‐free mass, body mass index, hematocrit, time after transplantation, and CYP3A5 genotype as covariates. The bias and imprecision were 0.35 and 1.38, respectively, in the external data set. Patients with functional CYP3A5 had 26% higher clearance and 37% lower bioavailability. Knowledge of CYP3A5 genotype provided an initial advantage, but only until 3‐4 tacrolimus concentrations were known. After this, a model without CYP3A5 genotype predicted just as well. The present models seem applicable for clinical individual dose predictions but need a prospective evaluation.