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In order to detect the two splice variant forms of type-IVB cyclic AMP phosphodiesterase (PDE) activity, DPD (type-IVB1) and PDE-4 (type-IVB2), anti-peptide antisera were generated. One set (‘DPD/PDE-4-common’), generated against a peptide sequence found at the common C-terminus of these two PDEs, detected both PDEs. A second set was PDE-4 specific, being directed against a peptide sequence found within the unique N-terminal region of PDE-4. In brain, DPD was found exclusively in the cytosol and PDE-4 exclusively associated with membranes. Both brain DPD and PDE-4 activities, isolated by immunoprecipitation, were cyclic AMP-specific (KmcyclicAMP: approximately 5 microM for DPD; approximately 4 microM for PDE-4) and were inhibited by low rolipram concentrations (K1rolipram approximately 1 microM for both). Transient expression of DPD in COS-1 cells allowed identification of an approx. 64 kDa species which co-migrated on SDS/PAGE with the immunoreactive species identified in both brain cytosol and membrane fractions using the DPD/PDE-4-common antisera. The subunit size observed for PDE-4 (approx. 64 kDa) in brain membranes was similar to that predicted from the cDNA sequence, but that observed for DPD was approx. 4 kDa greater. Type-IV, rolipram-inhibited PDE activity was found in all brain regions except the pituitary, where it formed between 30 and 70% of the PDE activity in membrane and cytosolic fractions when assayed with 1 microM cyclic AMP, PDE-4 formed 40-50% of the membrane type-IV activity in all brain regions save the midbrain (approx. 20%). DPD distribution was highly restricted to certain regions, providing approx. 35% of the type-IV cytosolic activity in hippocampus and 13-21% in cortex, hypothalamus and striatum with no presence in brain stem, cerebellum, midbrain and pituitary. The combined type-IVB PDE activities of DPD and PDE-4 contributed approx. 10% of the total PDE activity in most brain regions except for the pituitary (zero) and the mid-brain (approx. 3%. The isolated cDNAs for DPD and PDE-4 appear to reflect transcription products which are expressed in vivo in brain. The unique N-terminal domain of PDE-4 is suggested to target this PDE to membranes in brain. Type-IVB PDEs are differentially expressed in various brain regions, indicating that there are tissue-specific controls on both the expression of the gene and the splicing of its products.

Speech and language-related functions tend to depend on the left hemisphere more than the right in most right-handed (dextral) participants. This relationship is less clear in non-right handed (adextral) people, resulting in surprisingly polarised opinion on whether or not they are as lateralised as right handers. The present analysis investigates this issue by largely ignoring methodological differences between the different neuroscientific approaches to language lateralization, as well as discrepancies in how dextral and adextral participants were recruited or defined. Here we evaluate the tendency for dextrals to be more left hemisphere dominant than adextrals, using random effects meta analyses. In spite of several limitations, including sample size (in the adextrals in particular), missing details on proportions of groups who show directional effects in many experiments, and so on, the different paradigms all point to proportionally increased left hemispheric dominance in the dextrals. These results are analysed in light of the theoretical importance of these subtle differences for understanding the cognitive neuroscience of language, as well as the unusual asymmetry in most adextrals.

The insula is a multimodal sensory integration structure that, in addition to serving as a gateway between somatosensory areas and limbic structures, plays a crucial role in autonomic nervous system function. While anatomical studies following the development of the insula have been conducted, currently, no studies have been published in human fetuses tracking the development of neuronal migration or of white matter tracts in the cortex. In this study, we aimed to follow the neuronal migration and subsequent maturation of axons in and around the insula in human fetal ages. Using high-angular resolution diffusion magnetic resonance imaging tractography, major white matter pathways to/from the insula and its surrounding operculum were identified at a number of time points during human gestation. Pathways likely linked to neuronal migration from the ventricular zone to the inferior frontal gyrus, superior temporal region, and the insular cortex were detected in the earliest gestational age studied (15 GW). Tractography reveals neuronal migration to areas surrounding the insula occurred at different time points. These results, in addition to demonstrating key time points for neuronal migration, suggest that neurons and axonal fiber pathways underlying the insula and its surrounding gyri mature differentially despite their relationship during cortical folding.

The lack of multivariate methods for decoding the representational content of interregional neural communication has left it difficult to know what information is represented in distributed brain circuit interactions. Here we present Multi-Connection Pattern Analysis (MCPA), which works by learning mappings between the activity patterns of the populations as a factor of the information being processed. These maps are used to predict the activity from one neural population based on the activity from the other population. Successful MCPA-based decoding indicates the involvement of distributed computational processing and provides a framework for probing the representational structure of the interaction. Simulations demonstrate the efficacy of MCPA in realistic circumstances. In addition, we demonstrate that MCPA can be applied to different signal modalities to evaluate a variety of hypothesis associated with information coding in neural communications. We apply MCPA to fMRI and human intracranial electrophysiological data to provide a proof-of-concept of the utility of this method for decoding individual natural images and faces in functional connectivity data. We further use a MCPA-based representational similarity analysis to illustrate how MCPA may be used to test computational models of information transfer among regions of the visual processing stream. Thus, MCPA can be used to assess the information represented in the coupled activity of interacting neural circuits and probe the underlying principles of information transformation between regions.

Reply to the article: Zou K, Maeda T, Michikawa M, Komano H. New amyloid plaques or a game of hide-and-seek? Int J Biol Sci 2008; 4:200-201. We appreciate, but disagree with, Zou et al's comments regarding potential technical issues in the in vivo imaging. Our control experiments, including explicit criteria for inclusion and exclusion of new plaques, the presence of other plaques in the field that are observed by the dyes, the use of different freely diffusible well characterized dyes (both topical application and intraperitoneal application for a dye that that we have previously formally demonstrated to readily cross the blood brain barrier) and concurrent imaging of neurites and blood vessels to ensure quality of imaging per se all, in our opinion, argue against their concerns.

Jiong Tao,1,2 Xianglan Wang,2 Zhiyong Zhong,1,2 Hongying Han,2 Sha Liu,3 Shenglin Wen,4 Nianhong Guan,2 Lingjiang Li1 1Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, 2Department of Psychiatry, The Third Affiliated Hospital of Sun Yat-sen University, 3Department of Radiology, Guangzhou Huiai Hospital, Guangzhou, 4Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China Background: Abnormalities in white matter (WM) have previously been reported in patients with obsessive–compulsive disorder (OCD). However, there was some inconsistency in the results obtained for altered regions of WM. The aim of this study was to investigate fractional anisotropy (FA) in the WM of the whole brain in patients with OCD by using diffusion tensor imaging (DTI).Methods: In total, 28 unmedicated patients with OCD and 28 healthy volunteers underwent DTI scan. A voxel-based analysis was used to compare FA values in WM of the two groups at a voxel threshold of P<0.005 with an extent threshold of k>72 voxels (P<0.05; Alphasim correction). Subsequently, correlation analysis was conducted in order to find the correlation between the mean FA values in significantly altered brain regions and Yale–Brown Obsessive Compulsive Scale (Y-BOCS) scores of the OCD patients.Results: Compared with healthy volunteers, the OCD patients had lower FA value in the left lingual gyrus, right midbrain, and right precuneus. There were no regions with significantly higher FA values in OCD patients compared with healthy volunteers. The mean FA values in the above regions (left lingual, r=0.019, P=0.923; right midbrain, r=-0.208, P=0.289; and right precuneus, r=-0.273, P=0.161) had no significant correlation with the Y-BOCS scores of the OCD patients.Conclusion: The findings of this study suggest that alterations in WM of the left lingual gyrus, right midbrain, and right precuneus are associated with the pathophysiology mechanism of OCD, and these microstructural alterations do not correlate with symptom severity of OCD. Keywords: white matter, diffusion tensor imaging, fractional anisotropy, obsessive–compulsive disorder

Familial risk for attention‐deficit hyperactivity disorder (ADHD) has been associated with changes in brain activity related to cognitive control. However, it is not clear whether changes in activation are the primary deficit or whether they are related to impaired communication between regions involved in this ability. We investigated whether (1) functional connectivity between regions involved in cognitive control was affected by familial risk and (2) changes were specific to these regions. Correlational seed analyses were used to investigate temporal covariance between cognitive control and motor regions in two independent samples of typically developing controls, subjects with ADHD and their unaffected siblings. In both samples, correlation coefficients between cognitive control regions were greater for typically developing controls than for subjects with ADHD, with intermediate values for unaffected siblings. Within the motor network, unaffected siblings showed correlations similar to typically developing children. There were no differences in activity between the brain regions involved. These data show that functional connectivity between cognitive control regions is sensitive to familial risk for ADHD. Results suggest that changes in connectivity associated with cognitive control may be suitable as an intermediate phenotype for future studies. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.

© 2020, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. Purpose of Review: This paper aims to review novel trends in cholinergic neuroimaging in Alzheimer and Lewy body parkinsonian disorders. Recent Findings: The spectrum of cholinergic imaging is expanding with the availability of spatially more precise radioligands that allow assessment of previously less recognized subcortical and cortical structures with more dense cholinergic innervation. In addition, advances in MRI techniques now allow quantitative structural or functional assessment of both the cholinergic forebrain and the pedunculopontine nucleus, which may serve as non-invasive prognostic predictors. Multimodal imaging approaches, such as PET-MRI or multiligand PET, offer new insights into the dynamic and interactive roles of the cholinergic system at both local and larger-scale neural network levels. Summary: Our understanding of the heterogeneous roles of the cholinergic system in age-related diseases is evolving. Multimodal imaging approaches that provide complimentary views of the cholinergic system will be necessary to shed light on the impact of cholinergic degeneration on regional and large-scale neural networks that underpin clinical symptom manifestation in neurodegeneration.