Cholinergic Pairing with Visual Activation Results in Long-Term Enhancement of Visual Evoked Potentials

Acetylcholine (ACh) contributes to learning processes by modulating cortical plasticity in terms of intensity of neuronal activity and selectivity properties of cortical neurons. However, it is not known if ACh induces long term effects within the primary visual cortex (V1) that could sustain visual learning mechanisms. In the present study we analyzed visual evoked potentials (VEPs) in V1 of rats during a 4–8 h period after coupling visual stimulation to an intracortical injection of ACh analog carbachol or stimulation of basal forebrain. To clarify the action of ACh on VEP activity in V1, we individually pre-injected muscarinic (scopolamine), nicotinic (mecamylamine), α7 (methyllycaconitine), and NMDA (CPP) receptor antagonists before carbachol infusion. Stimulation of the cholinergic system paired with visual stimulation significantly increased VEP amplitude (56%) during a 6 h period. Pre-treatment with scopolamine, mecamylamine and CPP completely abolished this long-term enhancement, while α7 inhibition induced an instant increase of VEP amplitude. This suggests a role of ACh in facilitating visual stimuli responsiveness through mechanisms comparable to LTP which involve nicotinic and muscarinic receptors with an interaction of NMDA transmission in the visual cortex.     

Reflection of the Emotional Significance of Visual Stimuli in the Characteristics of Evoked EEG Potentials

Healthy subjects (n = 88) were asked to passively visualize positive and passive emotiogenic visual stimuli and also stimuli with a neutral emotional content. Images of the International Affective Picture System (IAPS) were used. Amplitude/time characteristics of the components of evoked EEG potentials (EPs), P1, N1, P2, N2, and P3 and topographic distribution of the latter components were analyzed. The latencies, amplitudes, and topography of the EP waves induced by presentation of positive and negative stimuli were found to be different from the respective values for the EPs induced by neutral stimuli. The level and pattern of these differences typical of different EP components were dissimilar and depended on the sign of the emotions. Specificities related to the valency of an identified stimulus were observed within nearly all stages of processing of visual signals, for the negative stimuli, beginning from an early stage of sensory analysis corresponding to the development of wave Р1. The latencies of components Р1 in the case of presentation of emotiogenic negative stimuli and those of components N1, N2, and Р3 in the case of presentation of the stimuli of both valencies were shorter than the latencies observed at neutral stimuli. The amplitude of component N2 at perception of positive stimuli was, on average, lower, while the Р3 amplitude at perception of all emotiogenic stimuli was higher than in the case of presentation of neutral stimuli. The time dynamics of topographic peculiarities of processing of emotiogenic information were complicated. Activation of the left hemisphere was observed during the earliest stages of perception, while the right hemisphere was activated within the intermediate stages. Generalized activation of the cortex after the action of negative signals and dominance of the left hemisphere under conditions of presentation of positive stimuli were observed only within the final stages. As is supposed, emotiogenic stimuli possess a greater biological significance than neutral ones, and this is why the former attract visual attention first; they more intensely activate the respective cortical zones, and the corresponding visual information is processed more rapidly. The observed effects were more clearly expressed in the case of action of negative stimuli; these effects involved more extensive cortical zones. These facts are indicative of the higher intensity of activating influences of negative emotiogenic stimuli on neutral systems of the higher CNS structures.     

Role of the Frontal Cortical Areas in the Analysis of Visual Stimuli at Conscious and Unconscious Levels

Event-related potentials (ERP) in response to complex target stimuli, which consisted of a central recognizable picture and a lateral masked image (analyzed at the unconscious level) were recorded in adult subjects and seven-year-old children. ERP components N200, N300, and P400/N400 had different topography and were differently pronounced in adults and children. In adult subjects, the N200 component that reflects the processing of a sensory stimulus was recorded in the temporo-parieto-occipital and occipital areas. In children, N200 was recorded in the caudal regions and the frontal areas of the cortex. Analysis of different waveforms obtained by subtraction of the ERP to the central stimulus from the ERP to the complex stimulus showed that unconscious stimulus processing in adult subjects is not reflected in the ERP structure. In children, an unconsciously processed image incorporated into a complex stimulus evokes processing negativity in the occipital and frontal cortical areas. Comparison of ERP in groups of children divided by their reflectivity/impulsivity showed that, predominantly, the left frontal area is involved in image analysis at the unconscious level in reflective children and, predominantly, the right frontal area participates in unconscious image analysis in impulsive children. It is suggested that the perfection of the visual recognition of a target stimulus, which contains additional unconsciously processed information, consists in growth of the involvement of the left-hemispheric mechanisms (with respective growth of significance of the left-hemispheric mechanisms) and in a decrease in the role of the frontal areas in analysis of sensory information.     

Visual Evoked Potentials and Disorders of Visual Function in Children Suffering from Cerebral Palsy

Using recording of visual evoked potentials (VEP), we examined 126 children (from 1 to 14 years old) suffering from spastic forms of cerebral palsy. In the overwhelming majority of cases (84.1%), we found in these patients significant modifications of the VEP related to dysfunctions of the visual analyzer system at different levels of the latter. We analyzed correlation of clinical manifestations of the disease with deviations of the VEP characteristics from the age norm. We conclude that an EEG examination, including VEP recording, allows one to obtain objective estimates of disorders of the visual function in the studied population of patients.     

Interictal Neurocognitive Processing of Visual Stimuli in Migraine: Evidence from Event-Related Potentials

Research has established decreased sensory habituation as a defining feature in migraine, while decreased cognitive habituation has only been found with regard to cognitive assessment of the relative probability of the occurrence of a stimulus event. Our study extended the investigation of interictal habituation in migraine to include cognitive processing when viewing of a series of visually-complex images, similar to those we encounter on the internet everyday. We examined interictal neurocognitive function in migraine from a habituation perspective, using a novel paradigm designed to assess how the response to a series of images changes over time. Two groups of participants--migraineurs (N = 25) and non-migraine controls (N = 25)--were asked to view a set of 232 unfamiliar logos in the context of a target identification task as their brain electrical responses were recorded via event-related potentials (ERPs). The set of logos was viewed serially in each of 10 separate trial blocks, with data analysis focusing on how the ERP responses to the logos in frontal electrodes from 200-600 ms changed across time within each group. For the controls, we found that the amplitude of the late positive potential (LPP) ERP component elicited by the logos had no significant change across trial blocks. In contrast, in migraineurs we found that the LPP significantly increased in amplitude across trial blocks, an effect consistent with a lack of habituation to visual stimuli seen in previous research. Our findings provide empirical support abnormal cognitive processing of complex visual images across time in migraineurs that goes beyond the sensory-level habituation found in previous research.     

Integration of Motion Responses Underlying Directional Motion Anisotropy in Human Early Visual Cortical Areas

Recent imaging studies have reported directional motion biases in human visual cortex when perceiving moving random dot patterns. It has been hypothesized that these biases occur as a result of the integration of motion detector activation along the path of motion in visual cortex. In this study we investigate the nature of such motion integration with functional MRI (fMRI) using different motion stimuli. Three types of moving random dot stimuli were presented, showing either coherent motion, motion with spatial decorrelations or motion with temporal decorrelations. The results from the coherent motion stimulus reproduced the centripetal and centrifugal directional motion biases in V1, V2 and V3 as previously reported. The temporally decorrelated motion stimulus resulted in both centripetal and centrifugal biases similar to coherent motion. In contrast, the spatially decorrelated motion stimulus resulted in small directional motion biases that were only present in parts of visual cortex coding for higher eccentricities of the visual field. In combination with previous results, these findings indicate that biased motion responses in early visual cortical areas most likely depend on the spatial integration of a simultaneously activated motion detector chain.     

Mechanisms of Selective Attention during Competitive Discrimination of Visual and Auditory Verbal Information: Positron Emission Tomography and Cortical Evoked Potential Studies

The mechanisms of selective verbal attention were studied under conditions of simultaneous delivery of speech signals via the visual and auditory channels. The investigation was based on the comparison and synthesis of data obtained by two methods: positron emission tomography (PET) and brain evoked potentials (EPs). A new approach was developed: complementary tasks were constructed in such a way that, despite principal methodological problems, the same phenomenon could be investigated in one paradigm in EP and PET studies. The results obtained by the two methods are in rather good agreement with respect to topography: the secondary and tertiary areas, as well as the associative brain areas, are involved in attention concentration, that is, selection of verbal information occurs at the level of cognitive processes. The combination of two complementary methods, PET and EP, allowed the processes of processing of sensory information and brain mechanisms of selective attention to be investigated much more completely. The PET studies contributed to further understanding of brain mechanisms evidencing where processing occurs and the EP method provided insight into the mechanism of how this information is processed inside the corresponding cortical areas. The finding that the activation of primary areas of the visual cortex is accompanied by the inhibition of visual information deserves attention. This conclusion can be considered highly significant because of the concordance of the two independent methods. How to interpret it is not yet clear. It is possible that, in the case of primary importance of verbal information and priority of the visual channel for the repression from consciousness of artificially irrelevant information, a safety mechanism is activated: the amplified signal enters the brain cortex, where it is retained in the short-term iconic memory. This enables a reaction to this stimulus (if necessary), in the presence of any additional sign involving selective attention.     

Reorganization of Receptive Fields of Cortical Field 21a Neurons and Formation of Responses to Moving Visual Stimuli

Using extracellular recording of spike activity from single neurons of field 21a of the cat neocortex, we examined in detail the spatial organization of receptive fields (RFs) of such cells after conditions of presentation of an immobile blinking light spot (a static RF) and moving visual stimuli (dynamic RFs). As was shown, the excitability of different RF subfields of a group of neurons possessing homogeneous on–off organization of the static RF changes significantly depended on the contrast, shape, dimension, orientation, and direction of movement of the applied mobile visual stimulus. This is manifested in changes in the number of discharge centers and shifts of their spatial localization. A hypothesis on the possible role of synchronous activation of the neurons neighboring the cell under study in the formation of an additional neuronal mechanism providing specialization of neuronal responses is proposed.     

Correspondences in the Behavior of the Electroretinogram and of the Potentials Evoked at the Visual Cortex

Electrical potentials from the eye (ERG) and from the contralateral visual cortex were recorded in response to flashes of white and of colored light of various intensities and durations. The evoked potentials were found to parallel the behavior of the ERG in several significant respects. Selective changes in the ERG brought about by increasing the light intensity and by light adaptation led to parallel selective changes in the cortical responses. The dual waves (b₁, b₂) of the ERG were found to have counterparts in two cortical waves (c₁, c₂) which, in respect to changes in light intensity and to light adaptation, behaved analogously to the two retinal components. The responses evoked at high intensity showed only the diphasic c₁-potential. As stimulus intensity was lowered the c₁-wave decreased in magnitude and a delayed c₂-component appeared. The c₂-potential increased in amplitude as light intensity of the flash was further reduced. Eventually the c₂-wave, too, decreased as stimulus reduction continued. There was no wave length specificity in regard to either the duplex b-waves or duplex cortical waves. Both appeared at all wave lengths from 454 mµ to 630 mµ. The two cortical waves evoked by brief flashes of colored light showed all the behavior to changes in stimulus intensity and to light adaptation that occurred with white light.     

Natural Selection and Functional Potentials of Human Noncoding Elements Revealed by Analysis of Next Generation Sequencing Data

Noncoding DNA sequences (NCS) have attracted much attention recently due to their functional potentials. Here we attempted to reveal the functional roles of noncoding sequences from the point of view of natural selection that typically indicates the functional potentials of certain genomic elements. We analyzed nearly 37 million single nucleotide polymorphisms (SNPs) of Phase I data of the 1000 Genomes Project. We estimated a series of key parameters of population genetics and molecular evolution to characterize sequence variations of the noncoding genome within and between populations, and identified the natural selection footprints in NCS in worldwide human populations. Our results showed that purifying selection is prevalent and there is substantial constraint of variations in NCS, while positive selectionis more likely to be specific to some particular genomic regions and regional populations. Intriguingly, we observed larger fraction of non-conserved NCS variants with lower derived allele frequency in the genome, indicating possible functional gain of non-conserved NCS. Notably, NCS elements are enriched for potentially functional markers such as eQTLs, TF motif, and DNase I footprints in the genome. More interestingly, some NCS variants associated with diseases such as Alzheimer''s disease, Type 1 diabetes, and immune-related bowel disorder (IBD) showed signatures of positive selection, although the majority of NCS variants, reported as risk alleles by genome-wide association studies, showed signatures of negative selection. Our analyses provided compelling evidence of natural selection forces on noncoding sequences in the human genome and advanced our understanding of their functional potentials that play important roles in disease etiology and human evolution.     

Neural Responses in Parietal and Occipital Areas in Response to Visual Events Are Modulated by Prior Multisensory Stimuli

The effect of multi-modal vs uni-modal prior stimuli on the subsequent processing of a simple flash stimulus was studied in the context of the audio-visual ‘flash-beep’ illusion, in which the number of flashes a person sees is influenced by accompanying beep stimuli. EEG recordings were made while combinations of simple visual and audio-visual stimuli were presented. The experiments found that the electric field strength related to a flash stimulus was stronger when it was preceded by a multi-modal flash/beep stimulus, compared to when it was preceded by another uni-modal flash stimulus. This difference was found to be significant in two distinct timeframes – an early timeframe, from 130–160 ms, and a late timeframe, from 300–320 ms. Source localisation analysis found that the increased activity in the early interval was localised to an area centred on the inferior and superior parietal lobes, whereas the later increase was associated with stronger activity in an area centred on primary and secondary visual cortex, in the occipital lobe. The results suggest that processing of a visual stimulus can be affected by the presence of an immediately prior multisensory event. Relatively long-lasting interactions generated by the initial auditory and visual stimuli altered the processing of a subsequent visual stimulus.     

Women with a History of Childhood Maltreatment Exhibit more Activation in Association Areas Following Non-Traumatic Olfactory Stimuli: A fMRI Study

Background

The aim of this study was investigating how women with a history of childhood maltreatment (CM) process non-threatening and non-trauma related olfactory stimuli. The focus on olfactory perception is based on the overlap of brain areas often proposed to be affected in CM patients and the projection areas of the olfactory system, including the amygdala, orbitofrontal cortex, insula and hippocampus.

Methods

Twelve women with CM and 10 controls participated in the study. All participants were, or have been, patients in a psychosomatic clinic. Participants underwent a fMRI investigation during olfactory stimulation with a neutral (coffee) and a pleasant (peach) odor. Furthermore, odor threshold and odor identification (Sniffin'' Sticks) were tested.

Principal Findings

Both groups showed normal activation in the olfactory projection areas. However, in the CM-group we found additionally enhanced activation in multiple, mainly neocortical, areas that are part of those involved in associative networks. These include the precentral frontal lobe, inferior and middle frontal structures, posterior parietal lobe, occipital lobe, and the posterior cingulate cortex.

Conclusions

The results indicate that in this group of patients, CM was associated with an altered processing of olfactory stimuli, but not development of a functional olfactory deficit. This complements other studies on CM insofar as we found the observed pattern of enhanced activation in associative and emotional regions even following non-traumatic olfactory cues.     

Changes in the Threshold of Generation of Action Potentials by Spinal Motoneurons under Conditions of Their Natural Activation

We estimated the peculiarities of changes in the threshold of generation of action potentials (APs) by spinal motoneurons (MNs) related to increases in the frequency of discharges evoked by adequate somatosensory stimulation. In experiments on decerebrated cats, we intracellularly recorded the membrane potential (MP) from MNs of the mm. gastrocnemius + soleus. Natural activation of MNs was provided by controlled stretching of the homonymous muscles; AP thresholds were measured using the first derivative of changes in the MP and statistical limits of variations of this derivative. In different cases, the threshold could either increase or decrease with a rise in the frequency; moreover, oppositely directed changes in the threshold could be observed in some MNs within different phases of stretch-evoked activities of these cells. Dissimilarities of the dependences of the thresholds on the AP frequency were clearly manifested in the case of short-lasting increases in the excitability of the MNs, which were usually observed at the beginning of microelectrode recording. We conclude that, under conditions of natural activation of spinal MNs, the pattern of modulation of the AP threshold upon different intensities of excitation is not strictly determined.     

Cortical Shape and Curvedness Analysis of Structural Deficits in Remitting and Non-Remitting Depression

In morphometric neuroimaging studies, the relationship between brain structural changes and the antidepressant treatment response in patients with major depressive disorder has been explored to search depression-trait biomarkers. Although patients were treated with serotonin-related drugs, whether the same treatment resulted in remission and non-remission in depressed patients is currently under investigation. We recruited 25 depressed patients and 25 healthy controls and acquired volumetric magnetic resonance imaging of each participant. We used the shape index and curvedness to classify cortical shapes and quantify shape complexities, respectively, in studying the pharmacological effect on brain morphology. The results showed that different regions of structural abnormalities emerged between remitting and non-remitting patients when contrasted with healthy controls. In addition to comparing structural metrics in each cortical parcellation, similar to the traditional voxel-based morphometric method, we highlighted the importance of structural integrity along the serotonin pathway in response to medication treatment. We discovered that disrupted serotonin-related cortical regions might cause non-remission to antidepressant treatment from a pharmacological perspective. The anomalous areas manifested in non-remitting patients were mainly in the frontolimbic areas, which can be used to differentiate remitting from non-remitting participants before medication treatment. Because non-remission is the failure to respond to treatment with serotonin-related drugs, our method may help clinicians choose appropriate medications for non-remitting patients.     

Effect of Sahaja Yoga Meditation on Auditory Evoked Potentials (AEP) and Visual Contrast Sensitivity (VCS) in Epileptics

The effect of Sahaja yoga meditation on 32 patients with primary idiopathic epilepsy on regular and maintained antiepileptic medication was studied. The patients were randomly divided into 3 groups: group I practiced Sahaja Yoga meditation twice daily for 6 months under proper guidance; group II practiced postural exercises mimicking the meditation for the same duration; and group III was the control group. Visual Contrast Sensitivity (VCS), Auditory Evoked Potentials (AEP), Brainstem Auditory Evoked Potentials (BAEP), and Mid Latency Responses (MLR) were recorded initially (0 month) and at 3 and 6 months for each group. There was a significant improvement in VCS following meditation practice in group I participants. Na, the first prominent negative peak of MLR and Pa, the positive peak following Na did not register changes in latency. The Na-Pa amplitude of MLR also showed a significant increase. There were no significant changes in the absolute and interpeak latencies of BAEP. The reduced level of stress following meditation practice may make patients more responsive to specific stimuli. Sahaja Yoga meditation appears to bring about changes in some of the electrophysiological responses studied in epileptic patients.     

The Orientation and Localization of Cortical Microtubules in Differentiating Conifer Tracheids during Cell Expansion

Arrays of cortical microtubules (MTs) on radial walls in differentiatingtracheids of Taxus cuspidata were randomly oriented when primarywalls formed. The orientation of MTs changed progressively fromlongitudinal to transverse as cells expanded. During formationof primary walls, MTs in differentiating tracheids disappearedlocally at sites of future intertracheal bordered pits. In furtherdifferentiated tracheids, circular bands of MTs were observedaround the edges of developing bordered pits. (Received July 17, 1996; Accepted November 11, 1996)     

Pain Modulation in Waking and Hypnosis in Women: Event-Related Potentials and Sources of Cortical Activity

Using a strict subject selection procedure, we tested in High and Low Hypnotizable subjects (HHs and LHs) whether treatments of hypoalgesia and hyperalgesia, as compared to a relaxation-control, differentially affected subjective pain ratings and somatosensory event-related potentials (SERPs) during painful electric stimulation. Treatments were administered in waking and hypnosis conditions. LHs showed little differentiation in pain and distress ratings between hypoalgesia and hyperalgesia treatments, whereas HHs showed a greater spread in the instructed direction. HHs had larger prefrontal N140 and P200 waves of the SERPs during hypnotic hyperalgesia as compared to relaxation-control treatment. Importantly, HHs showed significant smaller frontocentral N140 and frontotemporal P200 waves during hypnotic hypoalgesia. LHs did not show significant differences for these SERP waves among treatments in both waking and hypnosis conditions. Source localization (sLORETA) method revealed significant activations of the bilateral primary somatosensory (BA3), middle frontal gyrus (BA6) and anterior cingulate cortices (BA24). Activity of these contralateral regions significantly correlated with subjective numerical pain scores for control treatment in waking condition. Moreover, multivariate regression analyses distinguished the contralateral BA3 as the only region reflecting a stable pattern of pain coding changes across all treatments in waking and hypnosis conditions. More direct testing showed that hypnosis reduced the strength of the association of pain modulation and brain activity changes at BA3. sLORETA in HHs revealed, for the N140 wave, that during hypnotic hyperalgesia, there was an increased activity within medial, supramarginal and superior frontal gyri, and cingulated gyrus (BA32), while for the P200 wave, activity was increased in the superior (BA22), middle (BA37), inferior temporal (BA19) gyri and superior parietal lobule (BA7). Hypnotic hypoalgesia in HHs, for N140 wave, showed reduced activity within medial and superior frontal gyri (BA9,8), paraippocampal gyrus (BA34), and postcentral gyrus (BA1), while for the P200, activity was reduced within middle and superior frontal gyri (BA9 and BA10), anterior cingulate (BA33), cuneus (BA19) and sub-lobar insula (BA13). These findings demonstrate that hypnotic suggestions can exert a top-down modulatory effect on attention/preconscious brain processes involved in pain perception.