精神分裂症记忆障碍研究进展

目的探讨精神分裂症患者的记忆障碍的现状及其病因,并介绍了某些记忆测验,为精神分裂症的研究和治疗提供科学依据。方法以最近10年国外有关精神分裂症研究的成果为基础,采用文献研究法分析总结了40余篇有关的研究成果。结果精神分裂症的记忆障碍涉及工作记忆、情节记忆、言语记忆、视觉记忆、空间记忆等等。神经生理方面的ERPs及神经影像学方面的fMRI显示精神分裂症存在记忆损伤。结论精神分裂症患者存在记忆障碍。     

Different slopes for different folks: Alpha and delta EEG power predict subsequent video game learning rate and improvements in cognitive control tasks

We hypothesized that control processes, as measured using electrophysiological (EEG) variables, influence the rate of learning of complex tasks. Specifically, we measured alpha power, event‐related spectral perturbations (ERSPs), and event‐related brain potentials during early training of the Space Fortress task, and correlated these measures with subsequent learning rate and performance in transfer tasks. Once initial score was partialled out, the best predictors were frontal alpha power and alpha and delta ERSPs, but not P300. By combining these predictors, we could explain about 50% of the learning rate variance and 10%–20% of the variance in transfer to other tasks using only pretraining EEG measures. Thus, control processes, as indexed by alpha and delta EEG oscillations, can predict learning and skill improvements. The results are of potential use to optimize training regimes.     

人脑不同计算思维方式的功能定位研究

本研究的目的是标定大脑在进行计算时其相应功能区域的解剖位置 ,并比较和探讨在执行连续默算减法和重复默读乘法表过程中在大脑中的激活模式。实验采用 14个右手习惯志愿者 ,在进行上述两种思考过程中 ,通过多断层回波技术 T2加权功能磁共振成像观察中枢激活反应。处理连续默算减法和重复默读乘法表这两种问题时的脑反应模式的截然不同证明 :大脑在处理连续默算减法和重复默读乘法表这两种任务时采用了完全不同的处理途径。连续默算减法的 (P<0 .0 1,T=5 .4 1)功能定位在额叶上、中回后部和顶叶后部小叶 ,证明了在计算和暂存记忆操作中 ,这些功能区域起着重要的作用 ;重复默读乘法表的 (P<0 .0 1,T=4 .77)功能定位仅在侧枕回两侧的一组激活簇。     

健康人大脑和小脑空间记忆认知功能的fMRI研究

本研究应用功能磁共振成像(functional magnetic resonance imaging,fMRI)技术,检测了健康人大脑和小脑参与空间记忆的认知过程。通过对10名右利手健康志愿者进行一项短时空间记忆任务作业的同时进行脑功能磁共振扫描,实验采用组块设计,任务与对照任务交替进行,数据采用SPM99软件进行数据分析和脑功能区定位。结果显示:当统计阈值设定为P<0.0001时,大脑皮层和右侧小脑一起被显著激活;大脑皮层所激活的脑区有双侧顶叶的楔前叶、顶上小叶、缘上回(BA7/40,BA:Brodma-nn Area),双侧前额上、中、下回(BA6/9/47),双侧枕叶和枕颞交界处(BA18/19/37),右侧海马回;左侧中脑黑质及被盖部也被激活。上述结果提示:小脑和大脑皮层一起参与了空间记忆的认知过程。     

Object‐substitution masking modulates spatial attention deployment and the encoding of information in visual short‐term memory: Insights from occipito‐parietal ERP components

If object‐substitution masking (OSM) arises from mask representations replacing target representations, OSM should impede the formation of representations in visual short‐term memory (VSTM). We utilized event‐related potentials to examine the effect of OSM on target processing. An N2pc was observed on trials with delayed‐offset masks, indicating that focused attention was directed to the target. The sustained posterior contralateral negativity (SPCN), an index of VSTM storage, was observed in delayed‐offset trials only on trials with correct responses. This supports the hypothesis that inaccurate performance on delayed‐offset trials arises from a failure to encode the target in VSTM. On co‐termination trials, accuracy was high and neither the N2pc nor SPCN was observed. This indicates that, in the absence of masking, the task was accomplished by maintaining a diffuse attentional state that enabled the joint encoding of the potential target items.     

Cognitive performance and electrophysiological indices of cognitive control: a validation study of conflict adaptation

Psychiatric and neurologic disorders are associated with deficits in the postconflict recruitment of cognitive control. The primary aim of this study was to validate the relationship between cognitive functioning and indices of conflict adaptation. Event-related potentials were obtained from 89 healthy individuals who completed an Eriksen flanker task. Neuropsychological domains tested included memory, verbal fluency, and attention/executive functioning. Behavioral measures and N2 amplitudes showed significant conflict adaptation (i.e., previous-trial congruencies influenced current-trial measures). Higher scores on the attention/executive functioning and verbal fluency domains were associated with larger incongruent-trial N2 conflict adaptation; measures of cognitive functioning were not related to behavioral indices. This study provides initial validation of N2 conflict adaptation effects as cognitive function-related aspects of cognitive control.     

Electrophysiological correlates of the maintenance of the representation of pitch objects in acoustic short-term memory

We studied the neuronal mechanisms that implement acoustic short-term memory (ASTM) for pitch using event-related potentials (ERP). Experiment 1 isolated an ERP component, the sustained anterior negativity (SAN), that increased in amplitude with increasing memory load in ASTM using stimuli with equal duration at all memory loads. The SAN load effect found in Experiment 1, when pitch had to be remembered to perform the task, was absent in Experiment 2 using the same sounds when memory was not required. In Experiment 3, the memory task was performed without or with concurrent articulatory suppression during the retention interval to prevent rehearsal via an articulatory loop. Load-related effects observed in Experiment 1 were found again, whether participants engaged in concurrent suppression or not. The results suggest that the SAN reflects activity required to maintain pitch objects in an ASTM system that is distinct from articulatory rehearsal.     

Spatial layout of letters in nonwords affects visual short‐term memory load: Evidence from human electrophysiology

The sustained posterior contralateral negativity (SPCN) was used to investigate the effect of spatial layout on the maintenance of letters in VSTM. SPCN amplitude was measured for words, nonwords, and scrambled nonwords. We reexamined the effects of spatial layout of letters on SPCN amplitude in a design that equated the mean frequency of use of each position. Scrambled letters that did not form words elicited a larger SPCN than either words or nonwords, indicating lower VSTM load for nonwords presented in a typical horizontal array than the load observed for the same letters presented in spatially scrambled locations. In contrast, prior research has shown that the spatial extent of arrays of simple stimuli did not influence the amplitude of the SPCN. Thus, the present results indicate the existence of encoding and VSTM maintenance mechanisms specific to letter and word processing.     

Echo train shifted multi-echo FLASH for functional MRI of the human brain at ultra-high spatial resolution

This paper describes the development of a novel technique for functional MRI of the human brain at 0.135 microL resolution for a whole brain section. In comparison with conventional studies at 3 mm isotropic resolution or 27 microL voxel size, the method yields an improvement by a factor of 200. To achieve optimum image quality, the approach is based on a multi-echo fast low-angle shot (FLASH) sequence with unipolar traversals of k-space in the frequency-encoding dimension and echo train shifting to avoid amplitude discontinuities in the phase-encoding dimension. These strategies ensure a smooth point-spread function and eliminate image ghosting artifacts without the need for any phase correction or other post-processing. Signal-to-noise losses due to the considerably reduced voxel sizes are compensated for by single slice acquisitions, optimized bandwidths and an experimental four-channel shoulder coil matched to the posterior portion of the head. Multi-echo FLASH studies of the human brain (2.9 T, seven echoes, 200 Hz/pixel bandwidth, effective echo time 36 ms, acquisition time 6 s) at 300 microm resolution (no interpolation) and 1.5 mm slice thickness revealed robust activations in primary visual areas in response to binocular stimulation. The new method holds promise for refined studies of the columnar organization of specific brain systems and for functional assessments of the gray matter at laminar resolution.     

Revisiting the incremental effects of context on word processing: Evidence from single‐word event‐related brain potentials

The amplitude of the N400—an event‐related potential (ERP) component linked to meaning processing and initial access to semantic memory—is inversely related to the incremental buildup of semantic context over the course of a sentence. We revisited the nature and scope of this incremental context effect, adopting a word‐level linear mixed‐effects modeling approach, with the goal of probing the continuous and incremental effects of semantic and syntactic context on multiple aspects of lexical processing during sentence comprehension (i.e., effects of word frequency and orthographic neighborhood). First, we replicated the classic word‐position effect at the single‐word level: Open‐class words showed reductions in N400 amplitude with increasing word position in semantically congruent sentences only. Importantly, we found that accruing sentence context had separable influences on the effects of frequency and neighborhood on the N400. Word frequency effects were reduced with accumulating semantic context. However, orthographic neighborhood was unaffected by accumulating context, showing robust effects on the N400 across all words, even within congruent sentences. Additionally, we found that N400 amplitudes to closed‐class words were reduced with incrementally constraining syntactic context in sentences that provided only syntactic constraints. Taken together, our findings indicate that modeling word‐level variability in ERPs reveals mechanisms by which different sources of information simultaneously contribute to the unfolding neural dynamics of comprehension.     

The pain matrix reloaded: a salience detection system for the body

Neuroimaging and neurophysiological studies have shown that nociceptive stimuli elicit responses in an extensive cortical network including somatosensory, insular and cingulate areas, as well as frontal and parietal areas. This network, often referred to as the "pain matrix", is viewed as representing the activity by which the intensity and unpleasantness of the perception elicited by a nociceptive stimulus are represented. However, recent experiments have reported (i) that pain intensity can be dissociated from the magnitude of responses in the "pain matrix", (ii) that the responses in the "pain matrix" are strongly influenced by the context within which the nociceptive stimuli appear, and (iii) that non-nociceptive stimuli can elicit cortical responses with a spatial configuration similar to that of the "pain matrix". For these reasons, we propose an alternative view of the functional significance of this cortical network, in which it reflects a system involved in detecting, orienting attention towards, and reacting to the occurrence of salient sensory events. This cortical network might represent a basic mechanism through which significant events for the body's integrity are detected, regardless of the sensory channel through which these events are conveyed. This function would involve the construction of a multimodal cortical representation of the body and nearby space. Under the assumption that this network acts as a defensive system signaling potentially damaging threats for the body, emphasis is no longer on the quality of the sensation elicited by noxious stimuli but on the action prompted by the occurrence of potential threats.     

The cognitive functions of the caudate nucleus

The basal ganglia as a whole are broadly responsible for sensorimotor coordination, including response selection and initiation. However, it has become increasingly clear that regions of the basal ganglia are functionally delineated along corticostriatal lines, and that a modular conception of the respective functions of various nuclei is useful. Here we examine the specific role of the caudate nucleus, and in particular, how this differs from that of the putamen. This review considers converging evidence from multiple domains including anatomical studies of corticostriatal circuitry, neuroimaging studies of healthy volunteers, patient studies of performance deficits on a variety of cognitive tests, and animal studies of behavioural control. We conclude that the caudate nucleus contributes to behaviour through the excitation of correct action schemas and the selection of appropriate sub-goals based on an evaluation of action-outcomes; both processes fundamental to successful goal-directed action. This is in contrast to the putamen, which appears to subserve cognitive functions more limited to stimulus-response, or habit, learning. This modular conception of the striatum is consistent with hierarchical models of cortico-striatal function through which adaptive behaviour towards significant goals can be identified (motivation; ventral striatum), planned (cognition; caudate) and implemented (sensorimotor coordination; putamen) effectively.     

Fundamental mechanisms of visual motion detection: models,cells and functions

Taking a comparative approach, data from a range of visual species are discussed in the context of ideas about mechanisms of motion detection. The cellular basis of motion detection in the vertebrate retina, sub-cortical structures and visual cortex is reviewed alongside that of the insect optic lobes. Special care is taken to relate concepts from theoretical models to the neural circuitry in biological systems. Motion detection involves spatiotemporal pre-filters, temporal delay filters and non-linear interactions. A number of different types of non-linear mechanism such as facilitation, inhibition and division have been proposed to underlie direction selectivity. The resulting direction-selective mechanisms can be combined to produce speed-tuned motion detectors. Motion detection is a dynamic process with adaptation as a fundamental property. The behavior of adaptive mechanisms in motion detection is discussed, focusing on the informational basis of motion adaptation, its phenomenology in human vision, and its cellular basis. The question of whether motion adaptation serves a function or is simply the result of neural fatigue is critically addressed.     

Seeing the invisible: the scope and limits of unconscious processing in binocular rivalry

When an image is presented to one eye and a very different image is presented to the corresponding location of the other eye, the two images compete for conscious representations, such that only one image is visible at a time while the other is suppressed. Called binocular rivalry, this phenomenon and its deviants have been extensively exploited to study the mechanism and neural correlates of consciousness. In this paper, we propose a framework - the unconscious binding hypothesis - to distinguish unconscious processing from conscious processing. According to this framework, the unconscious mind not only encodes individual features but also temporally binds distributed features to give rise to cortical representations; unlike conscious binding, however, unconscious binding is fragile. Under this framework, we review evidence from psychophysical and neuroimaging studies and come to two important conclusions. First, processing of invisible features depends on the "level" of the features as defined by their neural mechanisms. For low-level simple features, prolonged exposure to visual patterns (e.g. tilt) and simple translational motion can alter the appearance of subsequent visible features (i.e. adaptation). For invisible high-level features, complex spiral motion cannot produce adaptation, nor can objects/words enhance subsequent processing of related stimuli (i.e. priming). Yet images of tools can activate the dorsal pathway. Second, processing of invisible features has functional significance. Although invisible central cues cannot orient attention, invisible erotic pictures in the periphery can nevertheless guide attention, likely through emotional arousal; reciprocally, the processing of invisible information can be modulated by attention.     

Astrocytes and human cognition: Modeling information integration and modulation of neuronal activity

Recent research focusing on the participation of astrocytes in glutamatergic tripartite synapses has revealed mechanisms that support cognitive functions common to human and other mammalian species, such as learning, perception, conscious integration, memory formation/retrieval and the control of voluntary behavior. Astrocytes can modulate neuronal activity by means of release of glutamate, d-serine, adenosine triphosphate and other signaling molecules, contributing to sustain, reinforce or depress pre- and post-synaptic membranes. We review molecular mechanisms present in tripartite synapses and model the cognitive role of astrocytes. Single protoplasmic astrocytes operate as a “Local Hub”, integrating information patterns from neuronal and glial populations. Two mechanisms, here modeled as the “domino” and “carousel” effects, contribute to the formation of intercellular calcium waves. As waves propagate through gap junctions and reach other types of astrocytes (interlaminar, polarized, fibrous and varicose projection), the active astroglial network functions as a “Master Hub” that integrates results of distributed processing from several brain areas and supports conscious states. Response of this network would define the effect exerted on neuronal plasticity (membrane potentiation or depression), behavior and psychosomatic processes. Theoretical results of our modeling can contribute to the development of new experimental research programs to test cognitive functions of astrocytes.     

Ammonia metabolism,the brain and fatigue; revisiting the link

This review addresses the ammonia fatigue theory in light of new evidence from exercise and disease studies and aims to provide a view of the role of ammonia during exercise. Hyperammonemia is a condition common to pathological liver disorders and intense or exhausting exercise. In pathology, hyperammonemia is linked to impairment of normal brain function and the onset of the neurological condition, hepatic encephalopathy. Elevated blood ammonia concentrations arise due to a diminished capacity for removal via the liver and lead to increased exposure of organs, such as the brain, to the toxic effects of ammonia. High levels of brain ammonia can lead to deleterious alterations in astrocyte morphology, cerebral energy metabolism and neurotransmission, which may in turn impact on the functioning of important signalling pathways within the neuron. Such changes are believed to contribute to the disturbances in neuropsychological function, in particular the learning, memory, and motor control deficits observed in animal models of liver disease and also patients with cirrhosis. Hyperammonemia in exercise occurs as a result of an increased production by contracting muscle, through adenosine monophosphate (AMP) deamination (the purine nucleotide cycle) and branched chain amino acid (BCAA) deamination prior to oxidation. Plasma concentrations of ammonia during exercise often achieve or exceed those measured in liver disease patients, resulting in increased cerebral uptake. In this article we propose that exercise-induced hyperammonemia may lead to concomitant disturbances in brain function, potentially through similar mechanisms underpinning pathology, which may impact on performance as fatigue or reduced function, especially during extreme exercise.     

Modulation of cortical excitability induced by repetitive transcranial magnetic stimulation: influence of timing and geometrical parameters and underlying mechanisms

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that activates neurons via generation of brief pulses of high-intensity magnetic field. If these pulses are applied in a repetitive fashion (rTMS), persistent modulation of neural excitability can be achieved. The technique has proved beneficial in the treatment of a number of neurological and psychiatric conditions. However, the effect of rTMS on excitability and the other performance indicators shows a considerable degree of variability across different sessions and subjects. The frequency of stimulation has always been considered as the main determinant of the direction of excitability modulation. However, interactions exist between frequency and several other stimulation parameters that also influence the degree of modulation. In addition, the spatial interaction of the transient electric field induced by the TMS pulse with the cortical neurons is another contributor to variability. Consideration of all of these factors is necessary in order to improve the consistency of the conditioning effect and to better understand the outcomes of investigations with rTMS. These user-controlled sources of variability are discussed against the background of the mechanisms that are believed to drive the excitability changes. The mechanism behind synaptic plasticity is commonly accepted as the driver of sustained excitability modulation for rTMS and indeed, plasticity and rTMS share many characteristics, but definitive evidence is lacking for this. It is more likely that there is a multiplicity of mechanisms behind the action of rTMS. The different mechanisms interact with each other and this will contribute to the variability of rTMS-induced excitability changes. This review investigates the links between rTMS and synaptic plasticity, describes their similarities and differences, and highlights a neglected contribution of the membrane potential. In summary, the principal aims of this review are (i) to discuss the different experimental and subject-related factors that contribute to the variability of excitability modulation induced by rTMS, and (ii) to discuss a generalized underlying mechanism for the excitability modulation.