ACTH 4-9 effects on the human visual event-related potential

Three oral doses (5, 10 and 20 mg) of an analog of ACTH 4-9 were compared with a vehicle control and d-amphetamine (10 mg). In a double-blind procedure, five men and five women were tested at weekly intervals with each treatment. In each session, four visual event-related potentials (ERPs) were recorded at hourly intervals. Visual ERPs were averaged from the electroencephalogram recorded from the left and right hemisphere. Dosage, time after administration, hemisphere of the brain and sex of the subject influenced the ERP. The ACTH 4-9 analog decreased amplitude of P100 but increased integrated activity of the ERP. This effect peaked at 60 minutes then "recovered." The effects of the peptide were more pronounced with doses of 5 and 10 mg, in the right hemisphere of men and in the left hemisphere of women. The findings indicated that the ACTH 4-9 analog influenced components of ERP commonly related to the perceptual/attentional state of the organism in a sexually dimorphic manner.     

Altered processing of sensorimotor feedback in schizophrenia

Schizophrenia is characterized by an altered sense of the reality, associated with hallucinations and delusions. Some theories suggest that schizophrenia is related to a deficiency of the system that generates information about the sensory consequences of the actions realized by the subject. This system monitors the reafferent information resulting from an action and allows its anticipation. In the present study, we examined visual-event-related potentials (ERPs) generated by a sensorimotor task in 15 patients with schizophrenia and 15 normal controls. The visual feedback from hand movements performed by the subjects was experimentally distorted. Behavioral results showed that patients were impaired in recognizing their own movements. The ERP signal in patients also differed from those of control subjects. In patients, the ERP waveform was affected during the early part of the response (200 ms). This early effect in schizophrenic patients reveals a modified processing of the visual consequence of their actions.     

Laterality of the olfactory event-related potential response

In experimental practice, odors are commonly applied to only one nostril for recordings of olfactory event-related potentials (OERPs), but the lateralization aspect of the OERP response is unclear regarding both stimulated nostril and cortical topography. The purpose of the present study was to investigate whether stimulated-nostril side affects OERP amplitudes and latencies and whether these potentials indicate lateralization of brain response in healthy, right-handed, young adults. OERPs were recorded from nine electrode sites in response to monorhinal stimulation with amyl acetate in 28 participants. The results showed a general increase in amplitude from frontal to parietal electrode sites (in particular for N1/P3) and generally larger amplitudes on the left hemisphere and midline than on the right hemisphere. There was no main effect of stimulated-nostril side on amplitude. Interactions indicated that N1/P2 amplitude was larger for left- than right-nostril stimulation and larger on the left hemisphere and midline than on the right hemisphere in left-nostril stimulation. No main effect or interactions of stimulated-nostril side over latencies were found and no effects on latencies of sagittal or coronal sites. These findings suggest a general parietal, left-hemisphere predominance in response amplitude to odorous stimulation and imply that either the left or the right nostril may be sufficient for accurate assessment of OERP latency in right-handed, young adults.     

Age-related changes in event-related potentials in visual discrimination tasks

Visual event-related potentials and reaction times in physical and semantic discrimination tasks were studied in 29 normal subjects between the ages of 21 and 74 years. The NA, N2 and P3 components of the evoked potential, and simple and GO/NOGO reaction times were observed in both kinds of discrimination. Significant age-related slowing of the GO/NOGO reaction time was observed only in the semantic discrimination task. The N2 and P3 latencies elicited by both the physical and semantic stimuli were significantly and positively correlated with age, although there was no significant correlation between the NA latency and age. The interpeak latency between N2 and P3 showed no age-related changes. The decline of cognitive information processing with advancing age was evident from the classification of a perceived event as reflected by the N2 component.     

Altered velocity processing in schizophrenia during pursuit eye tracking

Smooth pursuit eye movements (SPEM) are needed to keep the retinal image of slowly moving objects within the fovea. Depending on the task, about 50%-80% of patients with schizophrenia have difficulties in maintaining SPEM. We designed a study that comprised different target velocities as well as testing for internal (extraretinal) guidance of SPEM in the absence of a visual target. We applied event-related fMRI by presenting four velocities (5, 10, 15, 20°/s) both with and without intervals of target blanking. 17 patients and 16 healthy participants were included. Eye movements were registered during scanning sessions. Statistical analysis included mixed ANOVAs and regression analyses of the target velocity on the Blood Oxygen Level Dependency (BOLD) signal. The main effect group and the interaction of velocity×group revealed reduced activation in V5 and putamen but increased activation of cerebellar regions in patients. Regression analysis showed that activation in supplementary eye field, putamen, and cerebellum was not correlated to target velocity in patients in contrast to controls. Furthermore, activation in V5 and in intraparietal sulcus (putative LIP) bilaterally was less strongly correlated to target velocity in patients than controls. Altered correlation of target velocity and neural activation in the cortical network supporting SPEM (V5, SEF, LIP, putamen) implies impaired transformation of the visual motion signal into an adequate motor command in patients. Cerebellar regions seem to be involved in compensatory mechanisms although cerebellar activity in patients was not related to target velocity.     

Altered platelet serotonin uptake kinetics in schizophrenia and depression

Platelet uptake of serotonin (5-HT) was studied in drug-free groups of normal controls, depressives and schizophrenics. The Michaelis constant was significantly higher in both the schizophrenics and the depressives than in the controls. The V_max did not differ significantly between the three groups. Uptake velocity at low substrate concentrations was significantly lower in the schizophrenic group and showed a similar trend in the depressives. There were no significant differences in K_m or V_max when depressives were subclassified as unipolar and bipolar. There were no significant correlations between 5-HT uptake kinetics and severity of illness. These findings raise the possibility of a structural defect in the 5-HT reuptake system in the major psychoses that reduces the affinity of the carrier for the amine. This alteration, if present in central serotonergic neurons, may play a role in the etiology and pathogenesis of depression and schizophrenia.     

Topography of visual event-related potentials during geometric and phonetic discriminations

Event-related potentials (ERPs) were obtained to letters during 3 tasks that involved a SIMPLE RESPONSE (SR) to each letter presentation, a FORM discrimination of the letters that formed a closed loop, and a RHYME discrimination of the letters that rhymed with the letter ‘v’. The first task only required detection of the letters, the FORM task required a visual-spatial analysis. and the RHYME task, a grapheme-phoneme conversion of the letters followed by a determination of rhyming characteristics. The SR ERPs were morphologically different from the discriminative ERPs, notably by the absence of N2 and P3. The difference wave forms between the discrimination and SR conditions and between the targets and non-targets indicated differential topographies of components associated with the FORM and RHYME tasks in the 300 msec latency region. In both of these tasks, components exhibited distributions localized primarily in the occipital regions, whereas in the RHYME task they extended more anteriorly and encompassed temporo-parietal regions. Thus, although the stimulus presentation was visual, the requirement of a visual-auditory conversion in the RHYME task resulted in activity that was more proximal to auditory regions than when only a FORM analysis of the letters was required.     

Diurnal variation in the P300 component of human cognitive event-related potential

Diurnal variation in the P300 component of the human cognitive event-related potential (ERP) was examined. The P300 component is considered to be a measure of neuroelectric activity related to cognitive functions such as attention allocation and information processing. Nine diurnally active healthy male subjects whose sleep-wake rhythms were synchronized prior to the experiment were studied. The P300 components oral temperature, heart rate, left- and right-hand grip strength, reaction time, subjectively rated sleepiness, attention level, and fatigue were measured at 08:00, 11:00, 14:00, 17:00, and 20:00. Significant diurnal variations in P300 latency, P300 amplitude, oral temperature, heart rate, left- and right-hand grip strength, subjectively rated sleepiness, and attention level were observed. The P300 latency at 08:00 was significantly longer than at 11:00, 17:00, and 20:00, while the P300 amplitude at 08:00 was significantly greater than at 17:00 and 20:00. The P300 latency was correlated positively with subjectively rated sleepiness and negatively correlated with subjectively rated attention level. These results suggest the existence of diurnal variation in human cognitive functions.     

Broad characterization of endogenous peptides in the tree shrew visual system

Endogenous neuropeptides, acting as neurotransmitters or hormones in the brain, carry out important functions including neural plasticity, metabolism and angiogenesis. Previous neuropeptide studies have focused on peptide-rich brain regions such as the striatum or hypothalamus. Here we present an investigation of peptides in the visual system, composed of brain regions that are generally less rich in peptides, with the aim of providing the first broad overview of peptides involved in mammalian visual functions. We target three important parts of the visual system: the primary visual cortex (V1), lateral geniculate nucleus (LGN) and superior colliculus (SC). Our study is performed in the tree shrew, a close relative of primates. Using a combination of data dependent acquisition and targeted LC-MS/MS based neuropeptidomics; we identified a total of 52 peptides from the tree shrew visual system. A total of 26 peptides, for example GAV and neuropeptide K were identified in the visual system for the first time. Out of the total 52 peptides, 27 peptides with high signal-to-noise-ratio (>10) in extracted ion chromatograms (EIC) were subjected to label-free quantitation. We observed generally lower abundance of peptides in the LGN compared to V1 and SC. Consistently, a number of individual peptides showed high abundance in V1 (such as neuropeptide Y or somatostatin 28) and in SC (such as somatostatin 28 AA1-12). This study provides the first in-depth characterization of peptides in the mammalian visual system. These findings now permit the investigation of neuropeptide-regulated mechanisms of visual perception.     

Auditory and visual event-related potentials in a controlled investigation of HIV infection

Auditory and visual event-related brain potentials (ERPs) were used to complement neuropsychological and medical assessment in neurologically healthy subjects with asymptomatic and symptomatic human immunodeficiency virus type 1 (HIV-1) infection. Auditory and visual ERPs, recorded using standard oddball paradigms, disclosed delays in late waves (N2 and P3) in symptomatic subjects (CDC stage IV) when compared with matched controls. Abnormally delayed P3 waves in at least one modality were recorded in 41% of symptomatics and this was associated with deficits in neuropsychological performance, particularly psychomotor slowing. However, no differences in late wave latencies between asymptomatic and control subjects were found, though asymptomatics showed delays in auditory N1 and P2 latencies. The number of morphological abnormalities, such as indiscernible late waves as well as topographical variability of the P3 wave, was increased in both HIV seropositive groups and possibly indicates a distinct mechanism of impairment, different from latency delay. Whilst P3 delay in symptomatics was not associated with changes in immune function (T4 cells) there was, however, a link with anaemia and subclinical hepatic dysfunction.     

Analysis of event-related potentials to verbal stimuli in healthy subjects and schizophrenia patients

In 30 healthy subjects and 32 patients after the first episode of schizophrenia 19 channel-EEG was recorded during visual presentation of a random sequence of words and pseudo-words. In the first series of the experiments, subjects had to read the presented verbal stimuli, in the second series they had to press a button when seeing a word, and in the third series they were instructed to press the button when seeing a pseudo-word. We studied components N170, P300 and N400. In the group of healthy subjects, the amplitude of N170 increased to words in the situation of their relevance, which corresponds to the "recognition potential", whereas in the group of patients, the amplitude of N170 increased to pseudo-words when they were relevant. So it was a paradoxical response. The amplitude of the ERP later waves (P300 and N400) in the group of schizophrenic patients was smaller and the relevance effect was impaired when the target stimuli were pseudo-words. However, the incongruity effect consisting in an increase in N400 amplitude to a non-target stimulus remained intact in patients.     

人脸感知中的事件相关电位早期成份反映了顺序性神经活动

事件相关电位(event.related potential,ERa)的研究证实了ERP的早期成份正电位P120、负电位N170和顶正波(vertexpositive potential,VPP)都与人脸感知活动有关.还有研究进一步表明,VPP是N170的正性配对成份,它们由同一大脑源活动产生.然而,P120是否也拥有...     

A visual metaphor describing neural dynamics in schizophrenia

Background

In many scientific disciplines the use of a metaphor as an heuristic aid is not uncommon. A well known example in somatic medicine is the ‘defense army metaphor’ used to characterize the immune system. In fact, probably a large part of the everyday work of doctors consists of ‘translating’ scientific and clinical information (i.e. causes of disease, percentage of succes versus risk of side-effects) into information tailored to the needs and capacities of the individual patient. The ability to do so in an effective way is at least partly what makes a clinician a good communicator. Schizophrenia is a severe psychiatric disorder which affects approximately 1% of the population. Over the last two decades a large amount of molecular-biological, imaging and genetic data have been accumulated regarding the biological underpinnings of schizophrenia. However, it remains difficult to understand how the characteristic symptoms of schizophrenia such as hallucinations and delusions are related to disturbances on the molecular-biological level. In general, psychiatry seems to lack a conceptual framework with sufficient explanatory power to link the mental- and molecular-biological domains.

Methodology/Principal Findings

Here, we present an essay-like study in which we propose to use visualized concepts stemming from the theory on dynamical complex systems as a ‘visual metaphor’ to bridge the mental- and molecular-biological domains in schizophrenia. We first describe a computer model of neural information processing; we show how the information processing in this model can be visualized, using concepts from the theory on complex systems. We then describe two computer models which have been used to investigate the primary theory on schizophrenia, the neurodevelopmental model, and show how disturbed information processing in these two computer models can be presented in terms of the visual metaphor previously described. Finally, we describe the effects of dopamine neuromodulation, of which disturbances have been frequently described in schizophrenia, in terms of the same visualized metaphor.

Conclusions/Significance

The conceptual framework and metaphor described offers a heuristic tool to understand the relationship between the mental- and molecular-biological domains in an intuitive way. The concepts we present may serve to facilitate communication between researchers, clinicians and patients.     

Visual cognitive dysfunction in depression: an event-related potential study

The P3(00) event-related potentials (ERPs) elicited by visual stimuli in two visual tasks were assessed in depressed patients (12 patients with major depression and 11 patients with bipolar disorder) and compared with those of 20 age-matched normal controls. At remission, the ERPs from 18 of the depressed patients were again recorded. The visual oddball (VO) paradigm presented both target and standard visual stimuli and the simple visual (SV) paradigm presented a target but no standard visual stimulus. Subjects performed the VO task significantly less accurately than the SV task, as reflected by the behavioral measures (reaction-time and task accuracy). Depressed patients of the bipolar group showed longer P3 peak latency for the VO task and no change in P3 amplitude. No significant differences were found in any other ERP component between the groups. During remission, slowing RTs and reduced P3 peak latencies were observed for both major depression and bipolar disorder groups. Thus, the P3 ERP may be an index of the contribution of the slowed central processing to psychomotor retardation in clinically homogenous samples of depressive patients performing an appropriately demanding task.     

Diurnal changes in the rabbit's visual evoked potential

Rabbits that have been exposed to the natural cycles of day and night exhibit marked diurnal changes in the shape of their Visual Evoked Potential in constant environmental conditions. The results of exposure to artificial 24 hr light-dark cycles strongly suggest that it is the regular alternation of daylight and darkness which acts as the synchronizing "Zeitgeber" for the V.E.P. rhythm which exists after exposure to the natural cycles of day and night. It would seem further that the V.E.P. changes reflect a square-wave like rhythm in the sensitivity of the visual system to photic stimuli, in which the sensitivity is much higher at night than in the day-time. The probable importance of the diurnal V.E.P. rhythm for the occurrence of daily fluctuations in behaviour is discussed.     

Altered small-world brain networks in schizophrenia patients during working memory performance

Impairment of working memory (WM) performance in schizophrenia patients (SZ) is well-established. Compared to healthy controls (HC), SZ patients show aberrant blood oxygen level dependent (BOLD) activations and disrupted functional connectivity during WM performance. In this study, we examined the small-world network metrics computed from functional magnetic resonance imaging (fMRI) data collected as 35 HC and 35 SZ performed a Sternberg Item Recognition Paradigm (SIRP) at three WM load levels. Functional connectivity networks were built by calculating the partial correlation on preprocessed time courses of BOLD signal between task-related brain regions of interest (ROIs) defined by group independent component analysis (ICA). The networks were then thresholded within the small-world regime, resulting in undirected binarized small-world networks at different working memory loads. Our results showed: 1) at the medium WM load level, the networks in SZ showed a lower clustering coefficient and less local efficiency compared with HC; 2) in SZ, most network measures altered significantly as the WM load level increased from low to medium and from medium to high, while the network metrics were relatively stable in HC at different WM loads; and 3) the altered structure at medium WM load in SZ was related to their performance during the task, with longer reaction time related to lower clustering coefficient and lower local efficiency. These findings suggest brain connectivity in patients with SZ was more diffuse and less strongly linked locally in functional network at intermediate level of WM when compared to HC. SZ show distinctly inefficient and variable network structures in response to WM load increase, comparing to stable highly clustered network topologies in HC.     

Discriminant analysis of event-related potential curves using smoothed principal components

Principal component analysis enhanced by the use of smoothing is used in conjunction with discriminant analysis techniques to devise a statistical classification method for the analysis of event-related potential data. A training set of premedication potentials collected from adolescents with attention-deficit hyperactive disorder (ADHD) is used to predict whether adolescents from an independent subject group will respond to long-term medication. Comparison of outcome prediction rates demonstrates that this method, which uses information from the whole ERP curve, is superior to the classification technique currently used by clinicians, which is based on a single ERP curve feature. The need to administer an initial dose of medication to classify patients is also eliminated.     

Functionally independent components of early event-related potentials in a visual spatial attention task.

Spatial visual attention modulates the first negative-going deflection in the human averaged event-related potential (ERP) in response to visual target and non-target stimuli (the N1 complex). Here we demonstrate a decomposition of N1 into functionally independent subcomponents with functionally distinct relations to task and stimulus conditions. ERPs were collected from 20 subjects in response to visual target and non-target stimuli presented at five attended and non-attended screen locations. Independent component analysis, a new method for blind source separation, was trained simultaneously on 500 ms grand average responses from all 25 stimulus-attention conditions and decomposed the non-target N1 complexes into five spatially fixed, temporally independent and physiologically plausible components. Activity of an early, laterally symmetrical component pair (N1aR and N1aL) was evoked by the left and right visual field stimuli, respectively. Component N1aR peaked ca. 9 ms earlier than N1aL. Central stimuli evoked both components with the same peak latency difference, producing a bilateral scalp distribution. The amplitudes of these components were no reliably augmented by spatial attention. Stimuli in the right visual field evoked activity in a spatio-temporally overlapping bilateral component (N1b) that peaked at ca. 180 ms and was strongly enhanced by attention. Stimuli presented at unattended locations evoked a fourth component (P2a) peaking near 240 ms. A fifth component (P3f) was evoked only by targets presented in either visual field. The distinct response patterns of these components across the array of stimulus and attention conditions suggest that they reflect activity in functionally independent brain systems involved in processing attended and unattended visuospatial events.     

High frequency components in the spectrum of the visual evoked potential

The occurrence of short term high frequency components in the spectra of the VEP is usually overshadowed by larger amplitude slow waves which occur simultaneously with the high frequency waves. The high frequency components become evident when the time varying power spectra of short duration (250 ms) segments of the VEP are examined. Two types of short duration time varying power spectra are considered: one is obtained directly from overlapping time segments of the average VEP; and, the other is obtained by computing the spectra from the average autocorrelation functions of overlapping time segments of the data following each stimulus. The first yields the time varying properties for the spectra of the stimulus-synchronized data while, the latter shows the time varying properties of both the synchronized and unsynchronized data present.