Complete in vitro DNA replication of SV40 chromatin in digitonin-treated permeable cells.

A permeable cell system has been developed by treatment with digitonin for studying in vitro DNA replication of chromatin. DNA replication of simian virus 40 nucleoprotein complexes (SV40 chromatin) in digitonin-treated permeable cells was analyzed by electrophoresis in agarose-gel. Autoradiography of the agarose-gel revealed that [32P]dCTP was incorporated in SV40 DNA I, II and replicating intermediates. The time course of the incorporation indicated the complete replication of SV40 DNA and chromatin with a full number of nucleosomes. The digitonin-treated permeable cell system will serve as a useful system for studying in vitro DNA replication of chromatin.</p

A computational model based on corticospinal functional MRI revealed asymmetrically organized motor corticospinal networks in humans

新規MRI技術で利き手の神経制御メカニズムを解明 --手指運動中の脳・脊髄機能結合パターンの左右差を世界で初めて計測--. 京都大学プレスリリース. 2022-08-08.Evolution of the direct, monosynaptic connection from the primary motor cortex to the spinal cord parallels acquisition of hand dexterity and lateralization of hand preference. In non-human mammals, the indirect, multi-synaptic connections between the bilateral primary motor cortices and the spinal cord also participates in controlling dexterous hand movement. However, it remains unknown how the direct and indirect corticospinal pathways work in concert to control unilateral hand movement with lateralized preference in humans. Here we demonstrated the asymmetric functional organization of the two corticospinal networks, by combining network modelling and simultaneous functional magnetic resonance imaging techniques of the brain and the spinal cord. Moreover, we also found that the degree of the involvement of the two corticospinal networks paralleled lateralization of hand preference. The present results pointed to the functionally lateralized motor nervous system that underlies the behavioral asymmetry of handedness in humans

Basal ganglia-cortical connectivity underlies self-regulation of brain oscillations in humans

Brain-Computer Interface操作の得手不得手に関わる脳回路を発見 --操作を「考える」か「感じる」か、個人差に合わせた技術開発へ期待--. 京都大学プレスリリース. 2022-08-10.Brain-computer interfaces provide an artificial link by which the brain can directly interact with the environment. To achieve fine brain-computer interface control, participants must modulate the patterns of the cortical oscillations generated from the motor and somatosensory cortices. However, it remains unclear how humans regulate cortical oscillations, the controllability of which substantially varies across individuals. Here, we performed simultaneous electroencephalography (to assess brain-computer interface control) and functional magnetic resonance imaging (to measure brain activity) in healthy participants. Self-regulation of cortical oscillations induced activity in the basal ganglia-cortical network and the neurofeedback control network. Successful self-regulation correlated with striatal activity in the basal ganglia-cortical network, through which patterns of cortical oscillations were likely modulated. Moreover, basal ganglia-cortical network and neurofeedback control network connectivity correlated with strong and weak self-regulation, respectively. The findings indicate that the basal ganglia-cortical network is important for self-regulation, the understanding of which should help advance brain-computer interface technology

Interactions across emotional, cognitive and subcortical motor networks underlying freezing of gait

Freezing of gait (FOG) is a gait disorder affecting patients with Parkinson's disease (PD) and related disorders. The pathophysiology of FOG is unclear because of its phenomenological complexity involving motor, cognitive, and emotional aspects of behavior. Here we used resting-state functional MRI to retrieve functional connectivity (FC) correlated with the New FOG questionnaire (NFOGQ) reflecting severity of FOG in 67 patients with PD. NFOGQ scores were correlated with FCs in the extended basal ganglia network (BGN) involving the striatum and amygdala, and in the extra-cerebellum network (CBLN) involving the frontoparietal network (FPN). These FCs represented interactions across the emotional (amygdala), subcortical motor (BGN and CBLN), and cognitive networks (FPN). Using these FCs as features, we constructed statistical models that explained 40% of the inter-individual variances of FOG severity and that discriminated between PD patients with and without FOG. The amygdala, which connects to the subcortical motor (BGN and CBLN) and cognitive (FPN) networks, may have a pivotal role in interactions across the emotional, cognitive, and subcortical motor networks. Future refinement of the machine learning-based classifier using FCs may clarify the complex pathophysiology of FOG further and help diagnose and evaluate FOG in clinical settings

Simulating developmental diversity: Impact of neural stochasticity on atypical flexibility and hierarchy

Introduction: Investigating the pathological mechanisms of developmental disorders is a challenge because the symptoms are a result of complex and dynamic factors such as neural networks, cognitive behavior, environment, and developmental learning. Recently, computational methods have started to provide a unified framework for understanding developmental disorders, enabling us to describe the interactions among those multiple factors underlying symptoms. However, this approach is still limited because most studies to date have focused on cross-sectional task performance and lacked the perspectives of developmental learning. Here, we proposed a new research method for understanding the mechanisms of the acquisition and its failures in hierarchical Bayesian representations using a state-of-the-art computational model, referred to as in silico neurodevelopment framework for atypical representation learning. Methods: Simple simulation experiments were conducted using the proposed framework to examine whether manipulating the neural stochasticity and noise levels in external environments during the learning process can lead to the altered acquisition of hierarchical Bayesian representation and reduced flexibility. Results: Networks with normal neural stochasticity acquired hierarchical representations that reflected the underlying probabilistic structures in the environment, including higher-order representation, and exhibited good behavioral and cognitive flexibility. When the neural stochasticity was high during learning, top-down generation using higher-order representation became atypical, although the flexibility did not differ from that of the normal stochasticity settings. However, when the neural stochasticity was low in the learning process, the networks demonstrated reduced flexibility and altered hierarchical representation. Notably, this altered acquisition of higher-order representation and flexibility was ameliorated by increasing the level of noises in external stimuli. Discussion: These results demonstrated that the proposed method assists in modeling developmental disorders by bridging between multiple factors, such as the inherent characteristics of neural dynamics, acquisitions of hierarchical representation, flexible behavior, and external environment.journal articl

Topographic representation of an occluded object and the effects of spatiotemporal context in human early visual areas.

モノの背後を見る脳の仕組みを解明 -視対象の部分像から全体像を復元する第1次視覚野の活動をfMRIで観察-. 京都大学プレスリリース. 2013-10-23.Occlusion is a primary challenge facing the visual system in perceiving object shapes in intricate natural scenes. Although behavior, neurophysiological, and modeling studies have shown that occluded portions of objects may be completed at the early stage of visual processing, we have little knowledge on how and where in the human brain the completion is realized. Here, we provide functional magnetic resonance imaging (fMRI) evidence that the occluded portion of an object is indeed represented topographically in human V1 and V2. Specifically, we find the topographic cortical responses corresponding to the invisible object rotation in V1 and V2. Furthermore, by investigating neural responses for the occluded target rotation within precisely defined cortical subregions, we could dissociate the topographic neural representation of the occluded portion from other types of neural processing such as object edge processing. We further demonstrate that the early topographic representation in V1 can be modulated by prior knowledge of a whole appearance of an object obtained before partial occlusion. These findings suggest that primary "visual" area V1 has the ability to process not only visible or virtually (illusorily) perceived objects but also "invisible" portions of objects without concurrent visual sensation such as luminance enhancement to these portions. The results also suggest that low-level image features and higher preceding cognitive context are integrated into a unified topographic representation of occluded portion in early areas

Neural mechanisms underlying deafferentation pain: a hypothesis from a neuroimaging perspective

Deafferentation pain following nerve injury annoys patients, and its management is a challenge in clinical practice. Although the mechanisms underlying deafferentation pain remain poorly understood, progress in the development of multidimensional neuroimaging techniques is casting some light on these issues. Deafferentation pain likely results from reorganization of the nervous system after nerve injury via processes that interact with the substrates for pain perception (the pain matrix). Therapeutic effects of motor cortex stimulation on deafferentation pain suggest that the core mechanisms underlying deafferentation pain also interact with the motor system. Therefore, simultaneous neuroimaging and brain stimulation, an emerging neuroimaging technique, was developed to investigate complicated interactions among motor, somatosensory, and pain systems. In healthy participants, parts of the pain matrix (the anterior cingulate cortex, parietal operculum, and thalamus) show activity during both somatosensory stimulation and brain stimulation to the motor cortex. This finding indicates that motor, somatosensory, and pain systems communicate among each other via the neural network. A better understanding of the plastic mechanisms influencing such cross-talk among these systems will help develop therapeutic interventions using brain stimulation and neurofeedback

Blunted diurnal interleukin-6 rhythm is associated with amygdala emotional hyporeactivity and depression: a modulating role of gene-stressor interactions

BackgroundThe immune system has major roles in the brain and related psychopathology. Disrupted interleukin-6 secretion and aberrant amygdala emotional reactivity are well-documented in stress-related mental disorders. The amygdala regulates psychosocial stress-related interleukin-6 affected by related genes. These led us to comprehensively examine the relationship between interleukin-6, amygdala activity, and stress-related mental symptoms under gene-stressor interactions.MethodsOne hundred eight nonclinical participants with various levels of anxiety/depression underwent magnetic resonance imaging scans during an emotional face task for amygdala activity and saliva collection (at 10-time points across 2 days) for the total output and diurnal patterns of interleukin-6. Gene-stressor interactions between rs1800796 (C/G) and rs2228145 (C/A) and stressful life events for the biobehavioral measures were explored.ResultsThe blunting of interleukin-6 diurnal pattern was associated with hypoactivation of the basolateral amygdala in response to fearful (vs. neutral) faces (t = 3.67, FWE-corrected p = 0.003), and was predominantly observed in individuals with rs1800796 C-allele homozygotes and negative life changes in the past year (F = 19.71, p &lt; 0.001). When considered in a comprehensive model, the diminished diurnal pattern predicted greater depressive symptoms (β = −0.40), modulated by the amygdala hypoactivity (β = 0.36) and rs1800796-stressor interactions (β = −0.41; all p &lt; 0.001).ConclusionHere we show that the blunted interleukin-6 diurnal rhythm predicts depressive symptoms, modulated by amygdala emotional hyporeactivity and gene-stressor interactions. These findings indicate a potential mechanism underlying vulnerability to depressive disorders, suggesting their early detection, prevention, and treatment through the understanding of immune system dysregulation

Effective Augmentation of Creativity-Involving Productivity Consequent to Spontaneous Selectivity in Knowledge Acquisition

The results of many studies have suggested that we actively select information from the environment. However, the functional consequences of such selectivity in knowledge acquisition remain unclear, even though it is a vital factor in determining the characteristics of our future knowledge and cognition. We hypothesized that spontaneous selectivity in knowledge acquisition results in effective augmentation of productivity, especially in creativity-demanding task. To test this, we conducted experiments in which subjects acquired novel compositional words during their rapid presentation, evaluated memory confidence rates for the acquired words, and then produced essays based on these words. First, in experiment 1, we showed that the level of confidence in the recognition memory for the words positively related with the length of the essays (a measure of creativity-involving productivity in quantity). Additionally, we found that the semantic distance from the essay to the components of the compositional word (a measure of creative-productivity in quality) was farther for the word with higher memory confidence than for the word with lower memory confidence, suggesting creative leaps when writing the former. While this result supported our hypothesis, it might also reflect better memory that was independent of spontaneous selection. Thus, in a different subject group, we conducted a similar experiment (experiment 2) in which two of the 20 compositional words were presented more often (five times per block) to force memorization. Again, consistent with our hypothesis, essays based on spontaneously memorized words (presented once per block) were significantly longer than those produced using the forcedly memorized words. Therefore, better memory per se did not explain the higher productivity. Instead, these results suggested that the higher creativity-involving productivity was consequent to spontaneous selectivity in the knowledge acquisition. Additionally, we propose a possible mechanism for the observed results based on the results of a neural network simulation. In this simulation, we found that novel information that was assigned to locations more easily accessible to the entire network was better assimilated and therefore selectively acquired. Based on this simulation, we moderately suggest that spontaneously acquired knowledge effectively confers productivity because it effectively activates large parts of the neural networks