Development of new potent agonists able to interact with two postulated subsites of the cholecystokinin CCK-B receptor

Since the biochemical and pharmacological profile of BC 197 and BC 264,two CCK₈-derived agonists with high specificity for CCK-Breceptors, suggests their potential interaction with two CCK-B receptorsubsites, it appeared essential to design new series of compounds that wouldbe able to discriminate between these two subsites. As CCK₄ isthe shortest fragment of CCK which interacts selectively with CCK-Breceptors, compounds derived from the C-terminal tetrapeptide domain of BC264, Boc-Trp-(NMe)Nle-Asp-Phe-NH₂, and of the cyclic compoundBC 197, were prepared. While RB 360(N-(cycloamido)--Me(R)Trp-[(2S)-2-amino-9-((cycloamido)carbonyl)nonanoyl]-Asp-Phe-NH₂), like BC 197, has a CCK-B₁ profilewith anxiogenic-like effects in the elevated plus-maze test, RB 400(HOOC-CH₂-CO-Trp-(NMe)Nle-Asp-Phe-NH₂), like BC264, seems to be a specific CCK-B₂ agonist, able to increaseattention and/or memory processes in the Y-maze test.     

A review on the cognitive function of information structure during language comprehension

During communication, information structure can be used to highlight the most relevant piece of information, so that sufficient amount of attention can be allocated to the most important information. This paper aims to review the cognitive function of information structure during language comprehension from a neurocognitve perspective. First, we gave a brief introduction to the concept of information structure that has been studied mostly in linguistic field. Then we introduced recent studies on information structure using electrophysiological and neuroimaging techniques. After that, we discussed the relationship between attention and language processing more generally. Finally, we discussed potential directions for future studies.     

Neurofunctional model of large-scale correlates of selective attention governed by stimulus-novelty

Multiple studies demonstrate the influence of the limbic system on the processing of sensory events and attentional guidance. But the mechanisms involved therein are yet not entirely clear. The close connection of handling incoming sensory information and memory retrieval, like in the case of habituation towards insignificant stimuli, suggests a crucial impact of the hippocampus on the direction of attention. In this paper we thus present a neurofunctional forward model of a hippocampal comparator function based on the theory of theta-regulated attention. Subsequently we integrated this comparator model into a multiscale framework for the simulation of evoked responses. The results of our simulations were compared to experimental data on electroencephalographic (EEG) correlates of habituation towards familiar stimuli using time-scale analysis. In consequence we are able to present additional evidence for limbic influences on the direction of attention driven by stimulus novelty and a systems neuroscience framework for the statements given in the theta-regulated attention hypothesis.     

Genetic factors of reaction time performance: DRD4 7‐repeat allele associated with slower responses

Twin studies indicate substantial inherited components in cognitive abilities. One of the most extensively studied candidate genes of cognitive functioning is the dopamine D4 receptor gene (DRD4), which has been suggested to be related to attentional disorders. Based on reaction time data of 245 Caucasians participating in different cognitive tasks, slower responses characterized the group with the 7‐repeat allele. This effect was present in both sexes and was not because of fatigue. To our knowledge, this is the first report on significant association (P = 0.0001) between the DRD4 variable number of tandem repeat (VNTR) polymorphism and response latencies in a non‐clinical adult sample. Other studied dopaminergic polymorphisms did not show an association with reaction time. These results illustrate that speed‐of‐performance measures derived from multiple reaction time tasks using standardization procedures could be promising tools to detect unique genetic effects in the background of cognitive abilities.     

调任通督针刺法联合感觉统合训练对注意缺陷多动障碍患儿注意力和脑动脉血流速度的影响

摘要 目的：观察感觉统合训练联合调任通督针刺法对注意缺陷多动障碍（ADHD）患儿注意力和脑动脉血流速度的影响。方法：纳入东莞市中医院2020年1月到2021年1月期间收治的ADHD患儿100例,入组患儿按门诊号单双数分为对照组（单数,感觉统合训练）和研究组（双数,调任通督针刺法联合感觉统合训练）,各为50例,两组患儿均干预3个月。观察并对比两组疗效、中医证候总积分、注意力、脑动脉血流速度、Conners父母评症状量表（PSQ）、联合型瑞文测验 (CRT) 评分。结果：研究组的临床总有效率明显高于对照组（P<0.05）。干预3个月后,两组注意力情况：错误数、漏报数较干预前减少,反应时间较干预前缩短,且研究组的变化程度大于对照组（P<0.05）。研究组患儿干预3个月后双侧中动脉（MCA）、前动脉（ACA）、后动脉（PCA）的血流速度均较干预前增快,且高于同时期的对照组患儿（P＜0.05）。干预3个月后,两组PSQ评分、中医证候总积分下降,CRT评分升高,且研究组的变化程度大于对照组（P<0.05）。结论：调任通督针刺法联合感觉统合训练可有效改善ADHD患儿注意力,促进临床症状改善,调节脑血流速度,临床应用价值较好。     

Vasopressin and vasotocin facilitate reversal of a brightness discrimination

Male albino rats received vasopressin, vasotocin, pressinoic acid or placebo and were tested on an aversively motivated brightness discrimination task. Treatment with both vasopressin and vasotocin had no effect on acquisition but facilitated the reversal of the discrimination. Pressinoic acid had an inconsistent effect. The results are interpreted to show that the C terminal of the peptides vasopressin and vasotocin influence potency of these peptides. Furthermore, the results are interpreted as showing that both vasotocin and vasopressin influence selective attention during aversively motivated tasks.     

Letter to the Editor: Seasonal Pattern of Births in Patients with Optic Neuritis

Attentional processes are fundamental to good cognitive functioning of human operators. The purpose of this study was to analyze the activity of neuronal networks involved in the orienting attention and executive control processes from the perspective of diurnal variability. Twenty-three healthy male volunteers meeting magnetic resonance (MR) inclusion criteria performed the Stroop Color-Word task (block design) in the MR scanner five times/day (06:00, 10:00, 14:00, 18:00, 22:00 h). The first scanning session was scheduled 1–1.5 h after waking. Between MR sessions, subjects performed simulated driving tasks in stable environmental conditions, with controlled physical activity and diet. Significant activation was found in brain regions related to the orienting attentional system: the parietal lobe (BA40) and frontal eye-fields (FEFs). There were also activations in areas of the executive control system: the fronto-insular cortex (FIC), dorsal anterior cingulate cortex (dACC), presupplementary motor area (preSMA), supplementary motor area (SMA), basal ganglia, middle temporal (MT; BA21), and dorsolateral prefrontal cortex (DLPFC), as a part of the central executive network. Significant deactivations were observed in the rostral anterior cingulate cortex (rACC), posterior cingulate cortex (PCC), superior frontal gyrus (SF), parietal lobe (BA39), and parahippocampal that are thought to comprise the default mode network (DMN). Additionally, the activated regions included bilaterally lingual gyrus and fusiform gyrus. The insula was bilaterally deactivated. Visual attention controlled by the goal-oriented attention system and comprising top-down and bottom-up mechanisms, activated by Stroop-like task, turned out to be prone to diurnal changes. The study results show the occurrence of time-of-day–related variations in neural activity of brain regions linked to the orienting attentional system (left parietal lobe—BA40, left and right FEFs), simultaneously providing arguments for temporal stability of the executive system and default mode network. These results also seem to suggest that the involuntary, exogenous (bottom-up) mechanism of attention is more vulnerable to circadian and fatigue factors than the voluntary (top-down) mechanism, which appear to be maintained at the same functional level during the day. The above phenomena were observed at the neural level. (Author correspondence: marek@uj.edu.pl)     

Attention-related,cross-modality modulation of somatosensory neurons in primate ventrobasal (VB) thalamus

Attention-related modulation (AM) of the somatosensory responses of single neurons has been demonstrated in the cerebral cortex and medullary dorsal horn, but not in the ventrobasal thalamus. The somatically evoked activity was recorded of single units in the ventral posterior lateral thalamus (VPL) of awake monkeys while they detected the termination of task-relevant somatic or visual stimuli. Eighteen of 56 somatically responsive VPL neurons are reported that were recorded for enough time for a complete analysis of their responses during both the visual and somatic attention tasks. All neurons were spontaneously active and responded either to innocuous cutaneous (13/18) or deep (5/18) stimuli. Seven neurons (7/18, 38.8%) showed AM of somatosensory responsiveness. Two cells (2/7, 28.6%) showed AM only during the visual task, two others (2/7, 28.6%) only during the somatosensory task, and three cells (3/7, 42.8%) showed AM during both tasks. All five cells showing AM during the somatosensory task had enhanced responses to the task-relevant somatic stimulus. In contrast, the somatosensory responses of all five cells showing AM during the visual task were reduced. It is concluded that selective attention is associated with a modality specific modulation of the somatosensory responses of a sub-population of neurons within the primate VPL nucleus.     

Event-related Potential Study of Novelty Processing Abnormalities in Autism

To better understand visual processing abnormalities in autism we studied the attention orienting related frontal event potentials (ERP) and the sustained attention related centro-parietal ERPs in a three stimulus oddball experiment. The three stimulus oddball paradigm was aimed to test the hypothesis that individuals with autism abnormally orient their attention to novel distracters as compared to controls. A dense-array 128 channel EGI electroencephalographic (EEG) system was used on 11 high-functioning children and young adults with autism spectrum disorder (ASD) and 11 age-matched, typically developing control subjects. Patients with ASD showed slower reaction times but did not differ in response accuracy. At the anterior (frontal) topography the ASD group showed significantly higher amplitudes and longer latencies of early ERP components (e.g., P100, N100) to novel distracter stimuli in both hemispheres. The ASD group also showed prolonged latencies of late ERP components (e.g., P2a, N200, P3a) to novel distracter stimuli in both hemispheres. However, differences were more profound in the right hemisphere for both early and late ERP components. Our results indicate augmented and prolonged early frontal potentials and a delayed P3a component to novel stimuli, which suggest low selectivity in pre-processing and later-stage under-activation of integrative regions in the prefrontal cortices. Also, at the posterior (centro-parietal) topography the ASD group showed significantly prolonged N100 latencies and reduced amplitudes of the N2b component to target stimuli. In addition, the latency of the P3b component was prolonged to novel distracters in the ASD group. In general, the autistic group showed prolonged latencies to novel stimuli especially in the right hemisphere. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. We propose the potential application of ERP evaluations in a novelty task as outcome measurements in the biobehavioral treatment (e.g., EEG biofeedback, TMS) of autism.