Review. Parallel studies of cocaine-related neural and cognitive impairment in humans and monkeys

Cocaine users display profound impairments in executive function. Of all the components of executive function, inhibition, or the ability to withhold responding, has been studied the most extensively and may be most impaired. Consistent with these deficits, evidence from imaging studies points to dysregulation in medial and ventromedial prefrontal cortices, areas activated during performance of inhibition tasks. Other aspects of executive function including updating, shifting and decision making are also deficient in cocaine users, and these deficits are paralleled by abnormalities in patterns of prefrontal cortical activation. The extent to which cocaine plays a role in these effects, however, is not certain, and cannot be determined solely on the basis of human studies. Investigations using a non-human primate model of increasing durations of cocaine exposure revealed that initially the effects of cocaine were restricted to ventromedial and orbital prefrontal cortices, but as exposure was extended the intensity and spatial extent of the effects on functional activity also expanded rostrally and laterally. Given the spatial overlap in prefrontal pathology between human and monkey studies, these longitudinal mapping studies in non-human primates provide a unique window of understanding into the dynamic neural changes that are occurring early in human cocaine abuse.     

正常人长时数字记忆信息提取的神经基础的功能磁共振研究

本文旨在通过功能磁共振成像(functional magnetic resonance imaging,fMRI)技术研究正常人进行长时数字记忆信息提取的神经基础。选取22名右利手志愿者进行长时数字记忆任务实验,采用组块设计,记忆任务与对照任务交替进行,同时利用Siemens 1.5T超导型磁共振仪进行fMRI成像,采用SPM99软件进行数据分析,脑功能区定位在Talairach坐标中显示。结果显示被试者在进行长时数字记忆提取任务时,激活最显著的皮层是左侧额中回(Brodmann分区9区,BA9区),另外左额叶内侧回、左额下回、右额下回、扣带回、左顶下小叶、左顶上小叶、右顶上小叶、右颞中回、左枕舌回、左枕中回、右中脑、小脑、右尾状核尾部等结构也有激活,各大脑皮层的激活均呈现明显的左侧半球优势。根据上述结果推论,长时数字记忆由以左侧大脑半球为优势的各脑区共同参与完成,其中左侧额叶外侧面可能是信息提取的重要结构,而其它脑叶及其之间的广泛联系可能在数字信息的加工、处理和存储中起重要作用。     

A beneficial effect of estrogen on working memory in postmenopausal women taking hormone replacement therapy

Recent neurophysiological data suggest that the prefrontal cortex (PFC) may be susceptible to modulation by estrogen. In humans, the PFC mediates a number of cognitive processes that contribute to memory function, particularly working memory. The present study examined whether memory tasks that recruit PFC-dependent information processing might exhibit estrogen sensitivity in women. Performance on several memory tasks, including measures of working memory, was evaluated in three groups of postmenopausal women: (1) women who were tested when taking estrogen only (n = 38, M(age) = 55.1 years), (2) women who were tested when taking estrogen and a progestin concurrently (n = 23, M(age) = 55.9 years), and (3) women who were not taking hormone replacement therapy (n = 35, M(age) = 56.0 years). Estrogen users exhibited significantly better performance on a verbal task and on a spatial task, each with a prominent working memory component, but did not differ from nonusers on control tasks involving simple passive recall. These findings are consistent with the hypothesis that estrogen is active within PFC and is capable of influencing functions dependent on this region. The results of this study raise the possibility that estrogen may play a role in maintaining certain frontal lobe functions in women.     

Interhemispheric transfer of working memories

1. Download : Download high-res image (125KB)
2. Download : Download full-size image

     

The effects of centrally administered fluorocitrate via inhibiting glial cells on working memory in rats

Although prefrontal and hippocampal neurons are critical for spatial working memory, the function of glial cells in spatial working memory remains uncertain. In this study we investigated the function of glial cells in rats’ working memory. The glial cells of rat brain were inhibited by intracerebroventricular (icv) injection of fluorocitrate (FC). The effects of FC on the glial cells were examined by using elec-troencephalogram (EEG) recordings and delayed spatial alternation tasks. After icv injection of 10 μL of 0.5 nmol/L or 5 nmol/L FC, the EEG power spectrum recorded from the hippocampus increased, but the power spectrum for the prefrontal cortex did not change, and working memory was unaffected. Fol-lowing an icv injection of 10 μL of 20 nmol/L FC, the EEG power spectra in both the prefrontal cortex and the hippocampus increased, and working memory improved. The icv injection of 10 μL of 50 nmol/L FC, the EEG power spectra in both the prefrontal cortex and in the hippocampus decreased, and working memory was impaired. These results suggest that spatial working memory is affected by cen-trally administered FC, but only if there are changes in the EEG power spectrum in the prefrontal cortex. Presumably, the prefrontal glial cells relate to the working memory.     

Circadian rhythms in phonological and visuospatial storage components of working memory

Working memory is a basic cognitive process that temporarily maintains the information necessary for the performance of many complex tasks such as reading comprehension, learning and reasoning. Working memory includes two storage components: phonological and visuospatial, and a central executive control. The objective of this study was to identify possible circadian rhythms in phonological and visuospatial storage components of working memory using a constant routine protocol. Participants were eight female undergraduate students, aged 17.5±0.93, range = 16 - 19 years old. They were recorded in the laboratory in a constant routine protocol during 30 h. Rectal temperature was recorded every minute; subjective sleepiness and tiredness, as well as phonological and visuospatial working memory tasks, were assessed each hour. There were circadian variations in correct responses in phonological and visuospatial working memory tasks. Cross-correlation analysis showed a 1-h phase delay of the phonological storage component and a 3-h phase delay of the visuospatial storage component with respect to rectal temperature. This result may explain the changes in the performance of many complex tasks during the day.     

Effects of neuromodulation in a cortical network model of object working memory dominated by recurrent inhibition

Experimental evidence suggests that the maintenance of an item in working memory is achieved through persistent activity in selective neural assemblies of the cortex. To understand the mechanisms underlying this phenomenon, it is essential to investigate how persistent activity is affected by external inputs or neuromodulation. We have addressed these questions using a recurrent network model of object working memory. Recurrence is dominated by inhibition, although persistent activity is generated through recurrent excitation in small subsets of excitatory neurons.Our main findings are as follows. (1) Because of the strong feedback inhibition, persistent activity shows an inverted U shape as a function of increased external drive to the network. (2) A transient external excitation can switch off a network from a selective persistent state to its spontaneous state. (3) The maintenance of the sample stimulus in working memory is not affected by intervening stimuli (distractors) during the delay period, provided the stimulation intensity is not large. On the other hand, if stimulation intensity is large enough, distractors disrupt sample-related persistent activity, and the network is able to maintain a memory only of the last shown stimulus. (4) A concerted modulation of GABA _A and NMDA conductances leads to a decrease of spontaneous activity but an increase of persistent activity; the enhanced signal-to-noise ratio is shown to increase the resistance of the network to distractors. (5) Two mechanisms are identified that produce an inverted U shaped dependence of persistent activity on modulation. The present study therefore points to several mechanisms that enhance the signal-to-noise ratio in working memory states. These mechanisms could be implemented in the prefrontal cortex by dopaminergic projections from the midbrain.     

Homeostatic and circadian regulation of cognitive performance

Cognitive processes are crucial for human performance. Basic cognitive processes, such as attention, working memory, and executive functions, show homeostatic (time awake, sleep deprivation) and circadian (time of day) variations. Each of these cognitive processes includes several components, which contribute sequentially to the homeostatic and circadian modulation of performance. Sudden (lapses) and gradual changes in cognitive performance occur with sleep deprivation or with time of day. The time course of human cognitive processes throughout the day is relevant to the programming of different human activities. The lowest level of cognitive performance occurs during nighttime and early in the morning, a better level occurs around noon, and even higher levels occur during afternoon and evening hours. However, this time course can be modulated by conditions such as chronotype, sleep deprivation, sleep disorders or medication that affects the central nervous system.     

Unexpected Rule-Changes in a Working Memory Task Shape the Firing of Histologically Identified Delay-Tuned Neurons in the Prefrontal Cortex

1. Download : Download high-res image (125KB)
2. Download : Download full-size image

     

A transient developmental increase in prefrontal activity alters network maturation and causes cognitive dysfunction in adult mice

1. Download : Download high-res image (155KB)
2. Download : Download full-size image

     

The relationship between visual working memory and attention: retention of precise colour information in the absence of effects on perceptual selection

We examined the conditions under which a feature value in visual working memory (VWM) recruits visual attention to matching stimuli. Previous work has suggested that VWM supports two qualitatively different states of representation: an active state that interacts with perceptual selection and a passive (or accessory) state that does not. An alternative hypothesis is that VWM supports a single form of representation, with the precision of feature memory controlling whether or not the representation interacts with perceptual selection. The results of three experiments supported the dual-state hypothesis. We established conditions under which participants retained a relatively precise representation of a parcticular colour. If the colour was immediately task relevant, it reliably recruited attention to matching stimuli. However, if the colour was not immediately task relevant, it failed to interact with perceptual selection. Feature maintenance in VWM is not necessarily equivalent with feature-based attentional selection.     

CDH13 is associated with working memory performance in attention deficit/hyperactivity disorder

Different analytic strategies, including linkage, association and meta-analysis support a role of CDH13 in the susceptibility to attention deficit/hyperactivity disorder (ADHD). CDH13 codes for cadherin 13 (or H-cadherin), which is a member of a family of calcium-dependent cell-cell adhesion proteins and a regulator of neural cell growth. We tested the association between CDH13 on three executive functioning tasks that are promising endophenotypes of ADHD. An adjusted linear regression analysis was performed in 190 ADHD-affected Dutch probands of the IMAGE project. Three executive functions were examined: inhibition, verbal and visuo-spatial working memory (WM). We tested 2632 single nucleotide polymorphisms (SNPs) within CDH13 and 20 kb up- and downstream of the gene (capturing regulatory sequences). To adjust for multiple testing within the gene, we applied stringent permutation steps. Intronic SNP rs11150556 is associated with performance on the Verbal WM task. No other SNP showed gene-wide significance with any of the analyzed traits, but a 72-kb SNP block located 446 kb upstream of SNP rs111500556 showed suggestive evidence for association (P-value range 1.20E-03 to 1.73E-04) with performance in the same Verbal WM task. This study is the first to examine CDH13 and neurocognitive functioning. The mechanisms underlying the associations between CDH13 and the clinical phenotype of ADHD and verbal WM are still unknown. As such, our study may be viewed as exploratory, with the results presented providing interesting hypotheses for further testing.     

Recognition memory for vibrotactile rhythms: An fMRI study in blind and sighted individuals

Calcarine sulcal cortex possibly contributes to semantic recognition memory in early blind (EB). We assessed a recognition memory role using vibrotactile rhythms and a retrieval success paradigm involving learned “old” and “new” rhythms in EB and sighted. EB showed no activation differences in occipital cortex indicating retrieval success but replicated findings of somatosensory processing. Both groups showed retrieval success in primary somatosensory, precuneus, and orbitofrontal cortex. The S1 activity might indicate generic sensory memory processes.     

Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome

1. Download : Download high-res image (170KB)
2. Download : Download full-size image