Alterations in Regional Homogeneity of Spontaneous Brain Activity in Late-Life Subthreshold Depression

The early detection of major depression in elderly individuals who are at risk of developing the disease is of prime importance when it comes to the prevention of geriatric depression. We used resting-state functional magnetic resonance imaging (fMRI) to examine changes in regional homogeneity (ReHo) of spontaneous activity in late-life subthreshold depression (StD), and we evaluated the sensitivity/specificity performance of these changes. Nineteen elderly individuals with StD and 18 elderly controls underwent a resting-state fMRI scan. The ReHo approach was employed to examine whether StD was related to alterations in resting-state neural activity, in the form of abnormal regional synchronization. Receiver operating characteristic curve analysis and the Fisher stepwise discriminant analysis were used to evaluate the sensitivity/specificity characteristics of the ReHo index in discriminating between the StD subjects and normal controls. The results demonstrated that, compared to controls, StD subjects display lower ReHo in the right orbitofrontal cortex (OFC), left dorsolateral prefrontal cortex (DLPFC), left postcentral gyrus (PCG), and left middle frontal and inferior temporal gyri, as well as higher ReHo in the bilateral insula and right DLPFC. The left PCG and the right DLPFC, OFC, and posterior insula, together reported a predictive accuracy of 91.9%. These results suggest that the regional activity coherence was changed in the resting brain of StD subjects, and that these alterations may serve as potential markers for the early detection of StD in late-life depression.     

Neurobiological approach to brain functional asymmetry in depression

The modern literature data were observed, which dedicated to the study of neurobiological mechanisms of depressive states of different origin. The results of the investigations of structurally functional features of depression in healthy volunteers in experiments and in patients with the neurological diseases were viewed. The data cited confirm the modern concepts of R. Davidson concerning to the role of brain functional asymmetry in depression: i.e., the associations between depression and a decrease of the functional activation of the left prefrontal lobe, and also the involving of amygdale in the processes of the forming of negative emotions and depression. The literature data observed and findings of our investigations allow us to conclude that depressive states are characterized not only by the decrease of the functional activity of the left hemisphere, especially, its prefrontal area, but also reciprocal increase of the physiological activity of the prefrontal area of the right hemisphere combined with right-hemispheric functional insufficiency, especially, of its posterior (parieto-temporal) areas.     

Correlation of EEG asymmetry and hypnotic susceptibility

Hypnosis research of the last decades confirmed that some cortical regions show characteristic modification of spontaneous brain electrical activity as a function of hypnotic responsiveness. Using FFT spectrum of 16 channel EEG recording, it was demonstrated that in highly susceptible subjects the right parieto-temporal region show more electric power than the left one while the low susceptibles have left side predominance or equilibrated power in all derivations. If a specific (Ericksonian) indirect hypnosis induction was administered, the same right side preponderance could be recorded in low susceptibles, too. On the basis of these results we can confirm the importance of the right parieto-temporal associative area in the alteration of consciousness characterizing hypnotic state.     

Murine GRPR and stathmin control in opposite directions both cued fear extinction and neural activities of the amygdala and prefrontal cortex

Extinction is an integral part of normal healthy fear responses, while it is compromised in several fear-related mental conditions in humans, such as post-traumatic stress disorder (PTSD). Although much research has recently been focused on fear extinction, its molecular and cellular underpinnings are still unclear. The development of animal models for extinction will greatly enhance our approaches to studying its neural circuits and the mechanisms involved. Here, we describe two gene-knockout mouse lines, one with impaired and another with enhanced extinction of learned fear. These mutant mice are based on fear memory-related genes, stathmin and gastrin-releasing peptide receptor (GRPR). Remarkably, both mutant lines showed changes in fear extinction to the cue but not to the context. We performed indirect imaging of neuronal activity on the second day of cued extinction, using immediate-early gene c-Fos. GRPR knockout mice extinguished slower (impaired extinction) than wildtype mice, which was accompanied by an increase in c-Fos activity in the basolateral amygdala and a decrease in the prefrontal cortex. By contrast, stathmin knockout mice extinguished faster (enhanced extinction) and showed a decrease in c-Fos activity in the basolateral amygdala and an increase in the prefrontal cortex. At the same time, c-Fos activity in the dentate gyrus was increased in both mutant lines. These experiments provide genetic evidence that the balance between neuronal activities of the amygdala and prefrontal cortex defines an impairment or facilitation of extinction to the cue while the hippocampus is involved in the context-specificity of extinction.     

Variable place-cell coupling to a continuously viewed stimulus: evidence that the hippocampus acts as a perceptual system.

A key feature of perception is that the interpretation of a single, continuously available stimulus can change from time to time. This aspect of perception is well illustrated by the use of ambiguous figures that can be seen in two different ways. When people view such a stimulus they almost universally describe what they are seeing as jumping between two states. If it is agreed that this perceptual phenomenon is causally linked to the activity of nerve cells, the state jumps would have to occur in conjunction with changes in neural activity somewhere in the nervous system. Our experiments suggest that hippocampal place cells are part of a perceptual system. We conducted variations of a ''cue-card rotation'' experiment on rats in which the angular position of a prominent visual stimulus on the wall of cylinder is changed in the rat''s presence. The three main results are that (i) place-cell firing fields remain stationary if the cue is rotated by 180 degrees, so the relation between the cue and the field is altered; (ii) firing fields rotate by 45 degrees when the cue is rotated by 45 degrees, so the relation between the field and the card is maintained; and (iii) if the cue is first rotated by 180 degrees and then rotated in a series of 45 degrees steps, the field winds up at a different angular position relative to the card when the card is back in its original position. Thus, place cells can fire in two different ways in response to a continuously viewed stimulus. We conclude that place cells reveal that the hippocampal mapping system also has properties expected of a perceptual system.     

猕猴前额叶皮层神经元在视觉延缓分辨活动中的放电活动

在已学会颜色延缓分辨的3只猕猴上,用钨丝微电极记录前额叶背外侧部皮层神经元的放电活动,着重分析神经元放电活动与颜色延缓分辨活动的各个时期之间的相互关系。延缓分辨任务开始时,同时把红色光和绿色光分别投射在测试板上的两个显示窗上,约持续1.2s(暗示期)。颜色光熄灭后2—4s(此为延缓期),各自位于每一显示窗下的两个反应键同时向猴方推出。自此,反应期开始,动物应马上有选择地作出按键反应。如果动物作出正确选择按红色光下的反应键,则给少量桔子汁作奖励。共记录了155个前额皮层单位。其中40个单位的放电频率在动物完成视觉延缓分辨作业过程中没有明显变化,另外115个单位与该任务的某些时期有关。大多数单位(n=99)在反应键推出时,或者在按反应键的前后有放电频率变化。这99个单位中,15个在暗示期和反应期内放电活动有变化(CR 型单位),13个在延缓期和反应期内放电活动有变化(DR 型单位),42个只在反应期内或反应期后放电频率出现变化(R 型单位),其余29个单位则在分辨任务的各个时期都显示出放电活动变化(CDR 型单位)。上述这些单位中,有少数单位在动物作出正确反应时的放电型式与动物作出错误反应时的放电型式有明显不同。此外,即使动物对任务测试不作出按键反应时,也观察到16个单位的放电活动在任     

Origins of spatial working memory deficits in schizophrenia: an event-related FMRI and near-infrared spectroscopy study

Abnormal prefrontal functioning plays a central role in the working memory (WM) deficits of schizophrenic patients, but the nature of the relationship between WM and prefrontal activation remains undetermined. Using two functional neuroimaging methods, we investigated the neural correlates of remembering and forgetting in schizophrenic and healthy participants. We focused on the brain activation during WM maintenance phase with event-related functional magnetic resonance imaging (fMRI). We also examined oxygenated hemoglobin changes in relation to memory performance with the near-infrared spectroscopy (NIRS) using the same spatial WM task. Distinct types of correct and error trials were segregated for analysis. fMRI data indicated that prefrontal activation was increased during WM maintenance on correct trials in both schizophrenic and healthy subjects. However, a significant difference was observed in the functional asymmetry of frontal activation pattern. Healthy subjects showed increased activation in the right frontal, temporal and cingulate regions. Schizophrenic patients showed greater activation compared with control subjects in left frontal, temporal and parietal regions as well as in right frontal regions. We also observed increased 'false memory' errors in schizophrenic patients, associated with increased prefrontal activation and resembling the activation pattern observed on the correct trials. NIRS data replicated the fMRI results. Thus, increased frontal activity was correlated with the accuracy of WM in both healthy control and schizophrenic participants. The major difference between the two groups concerned functional asymmetry; healthy subjects recruited right frontal regions during spatial WM maintenance whereas schizophrenic subjects recruited a wider network in both hemispheres to achieve the same level of memory performance. Increased "false memory" errors and accompanying bilateral prefrontal activation in schizophrenia suggest that the etiology of memory errors must be considered when comparing group performances. Finally, the concordance of fMRI and NIRS data supports NIRS as an alternative functional neuroimaging method for psychiatric research.     

On the Quantification of SSVEP Frequency Responses in Human EEG in Realistic BCI Conditions

This article concerns one of the most important problems of brain-computer interfaces (BCI) based on Steady State Visual Evoked Potentials (SSVEP), that is the selection of the a-priori most suitable frequencies for stimulation. Previous works related to this problem were done either with measuring systems that have little in common with actual BCI systems (e.g., single flashing LED) or were presented on a small number of subjects, or the tested frequency range did not cover a broad spectrum. Their results indicate a strong SSVEP response around 10 Hz, in the range 13–25 Hz, and at high frequencies in the band of 40–60 Hz. In the case of BCI interfaces, stimulation with frequencies from various ranges are used. The frequencies are often adapted for each user separately. The selection of these frequencies, however, was not yet justified in quantitative group-level study with proper statistical account for inter-subject variability. The aim of this study is to determine the SSVEP response curve, that is, the magnitude of the evoked signal as a function of frequency. The SSVEP response was induced in conditions as close as possible to the actual BCI system, using a wide range of frequencies (5–30 Hz, in step of 1 Hz). The data were obtained for 10 subjects. SSVEP curves for individual subjects and the population curve was determined. Statistical analysis were conducted both on the level of individual subjects and for the group. The main result of the study is the identification of the optimal range of frequencies, which is 12–18 Hz, for the registration of SSVEP phenomena. The applied criterion of optimality was: to find the largest contiguous range of frequencies yielding the strong and constant-level SSVEP response.     

Contributions of the amygdala to reward expectancy and choice signals in human prefrontal cortex

The prefrontal cortex (PFC) receives substantial anatomical input from the amygdala, and these two structures have long been implicated in reward-related learning and decision making. Yet little is known about how these regions interact, especially in humans. We investigated the contribution of the amygdala to reward-related signals in PFC by scanning two rare subjects with focal bilateral amygdala lesions using fMRI. The subjects performed a reversal learning task in which they first had to learn which of two choices was the more rewarding, and then flexibly switch their choices when contingencies changed. Compared with healthy controls, both amygdala lesion subjects showed a profound change in ventromedial prefrontal cortex (vmPFC) activity associated with reward expectation and behavioral choice. These findings support a critical role for the human amygdala in establishing expected reward representations in PFC, which in turn may be used to guide behavioral choice.     

Altered Regional Homogeneity with Short-term Simulated Microgravity and Its Relationship with Changed Performance in Mental Transformation

In order to further the insight into the explanation of changed performance in mental transformation under microgravity, we discuss the change of performance in mental transformation and its relationship with altered regional homogeneity (ReHo) in resting-state brain by using simulated weightlessness model. Twelve male subjects with age between 24 and 31 received resting-state fMRI scan and mental transformation test both in normal condition and immediately after 72 hours −6° head down tilt (HDT). A paired sample t-test was used to test the difference of behavior performance and brain activity between these two conditions. Compare with normal condition, subjects showed a changed performance in mental transformation with short term simulated microgravity and appeared to be falling. Meanwhile, decreased ReHo were found in right inferior frontal gyrus (IFG) and left inferior parietal lobule (IPL) after 72 hours −6° HDT, while increased ReHo were found in bilateral medial frontal gyrus (MFG) and left superior frontal gyrus (SFG) (P<0.05, corrected). Particularly, there was a significant correlation between ReHo values in left IPL and velocity index of mental transformation. Our findings indicate that gravity change may disrupt the function of right IFG and left IPL in the resting-state, among of which functional change in left IPL may contribute to changed abilities of mental transformation. In addition, the enhanced activity of the bilateral MFG and decreased activity of right IFG found in the current study maybe reflect a complementation effect on inhibitory control process.     

What Happens in Between? Human Oscillatory Brain Activity Related to Crossmodal Spatial Cueing

Previous studies investigated the effects of crossmodal spatial attention by comparing the responses to validly versus invalidly cued target stimuli. Dynamics of cortical rhythms in the time interval between cue and target might contribute to cue effects on performance. Here, we studied the influence of spatial attention on ongoing oscillatory brain activity in the interval between cue and target onset. In a first experiment, subjects underwent periods of tactile stimulation (cue) followed by visual stimulation (target) in a spatial cueing task as well as tactile stimulation as a control. In a second experiment, cue validity was modified to be 50%, 75%, or else 25%, to separate effects of exogenous shifts of attention caused by tactile stimuli from that of endogenous shifts. Tactile stimuli produced: 1) a stronger lateralization of the sensorimotor beta-rhythm rebound (15-22 Hz) after tactile stimuli serving as cues versus not serving as cues; 2) a suppression of the occipital alpha-rhythm (7-13 Hz) appearing only in the cueing task (this suppression was stronger contralateral to the endogenously attended side and was predictive of behavioral success); 3) an increase of prefrontal gamma-activity (25-35 Hz) specifically in the cueing task. We measured cue-related modulations of cortical rhythms which may accompany crossmodal spatial attention, expectation or decision, and therefore contribute to cue validity effects. The clearly lateralized alpha suppression after tactile cues in our data indicates its dependence on endogenous rather than exogenous shifts of visuo-spatial attention following a cue independent of its modality.     

The effect of scopolamine on the spatial organization of rat cortical potentials

The influence of scopolamine (1 mg/kg, i.p.) on the spatial organization of the neocortical electrical activity was studied in rats. A decrease in the spectral power and coherence of brain potentials in the range of the dominant theta-rhythm peak (6.00-7.25 Hz) and their increase in the adjacent low-frequency band were observed. Both indices were decreased in the wide beta band (19.00-30.00 Hz). The described changes took place over the whole areas of the right hemisphere and parieto-temporal region of the left hemisphere. The obtained results are discussed with respect to the role of the cholinergic brain system in the higher nervous activity.     

Right prefrontal activity reflects the ability to overcome sleepiness during working memory tasks: a functional near-infrared spectroscopy study

It has been speculated that humans have an inherent ability to overcome sleepiness that counteracts homeostatic sleep pressure. However, it remains unclear which cortical substrate activities are involved in the ability to overcome sleepiness during the execution of cognitive tasks. Here we sought to confirm that this ability to overcome sleepiness in task execution improves performance on cognitive tasks, showing activation of neural substrates in the frontal cortex, by using a modified n-back (2- and 0-back) working memory task and functional near-infrared spectroscopy. The change in alertness was just correlated with performances on the 2-back task. Activity in the right prefrontal cortex changed depending on alertness changes on the 2- and 0-back tasks independently, which indicates that activity in this region clearly reflects the ability to overcome sleepiness; it may contribute to the function of providing sufficient activity to meet the task load demands. This study reveals characteristics of the ability to overcome sleepiness during the n-back working memory task which goes beyond the attention-control function traditionally proposed.     

Reorganization of interhemispheric interactions during verbal-mental activity aimed at synthesis of words and sentences

Correlation and coherence analyses of multichannel electroencephalogram (EEG) recordings from 18 subjects (mean age 25 years) were used for investigating the reorganization of systemic interactions between bioelectric potentials of the cortical areas of both hemispheres (20 EEG derivations) during verbal-mental activity connected with generating verbal units from simpler components. When generating either words from aurally presented phonemes or sentences from a set of words, the subjects exhibited specific changes in the spatial structure of the statistical relationships in the EEG, with a significant increase in the interhemispheric interactions. During performance of both tasks, the changes in the interhemispheric interactions were most pronounced in the temporal, temporo-parieto-occipital (TPO), inferofrontal, and occipital areas of both hemispheres. Phonemic synthesis was associated with a more marked increase in the contralateral interactions in the left hemisphere, and generating sentences from words, in the right hemisphere. The coherence analysis of the EEG showed the greatest changes in the Δ, ?, and β frequency bands, with rather slight changes in the α frequency band. For all frequency bands, changes in the EEG coherences were the greatest in Wernicke’s and the TPO areas of the right and left hemispheres during the performance of both tasks, especially during the phonemic synthesis. These findings suggest that neurophysiological processes underlying mental generation of words and sentences require coordinated activity of the left and right hemispheres, which is accompanied by an increase in the interhemispheric interactions in the EEG, especially in the temporal, inferofrontal, and TPO areas.     

Subtle Alterations in Brain Anatomy May Change an Individual’s Personality in Chronic Pain

It is well established that gross prefrontal cortex damage can affect an individual’s personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual’s personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual’s personality.     

Temporal Dynamics of Visual Attention Measured with Event-Related Potentials

How attentional modulation on brain activities determines behavioral performance has been one of the most important issues in cognitive neuroscience. This issue has been addressed by comparing the temporal relationship between attentional modulations on neural activities and behavior. Our previous study measured the time course of attention with amplitude and phase coherence of steady-state visual evoked potential (SSVEP) and found that the modulation latency of phase coherence rather than that of amplitude was consistent with the latency of behavioral performance. In this study, as a complementary report, we compared the time course of visual attention shift measured by event-related potentials (ERPs) with that by target detection task. We developed a novel technique to compare ERPs with behavioral results and analyzed the EEG data in our previous study. Two sets of flickering stimulus at different frequencies were presented in the left and right visual hemifields, and a target or distracter pattern was presented randomly at various moments after an attention-cue presentation. The observers were asked to detect targets on the attended stimulus after the cue. We found that two ERP components, P300 and N2pc, were elicited by the target presented at the attended location. Time-course analyses revealed that attentional modulation of the P300 and N2pc amplitudes increased gradually until reaching a maximum and lasted at least 1.5 s after the cue onset, which is similar to the temporal dynamics of behavioral performance. However, attentional modulation of these ERP components started later than that of behavioral performance. Rather, the time course of attentional modulation of behavioral performance was more closely associated with that of the concurrently recorded SSVEPs analyzed. These results suggest that neural activities reflected not by either the P300 or N2pc, but by the SSVEPs, are the source of attentional modulation of behavioral performance.     

Neural Mechanism of Facilitation System during Physical Fatigue

An enhanced facilitation system caused by motivational input plays an important role in supporting performance during physical fatigue. We tried to clarify the neural mechanisms of the facilitation system during physical fatigue using magnetoencephalography (MEG) and a classical conditioning technique. Twelve right-handed volunteers participated in this study. Participants underwent MEG recording during the imagery of maximum grips of the right hand guided by metronome sounds for 10 min. Thereafter, fatigue-inducing maximum handgrip trials were performed for 10 min; the metronome sounds were started 5 min after the beginning of the handgrip trials. The metronome sounds were used as conditioned stimuli and maximum handgrip trials as unconditioned stimuli. The next day, they were randomly assigned to two groups in a single-blinded, two-crossover fashion to undergo two types of MEG recordings, that is, for the control and motivation sessions, during the imagery of maximum grips of the right hand guided by metronome sounds for 10 min. The alpha-band event-related desynchronizations (ERDs) of the motivation session relative to the control session within the time windows of 500 to 700 and 800 to 900 ms after the onset of handgrip cue sounds were identified in the sensorimotor areas. In addition, the alpha-band ERD within the time window of 400 to 500 ms was identified in the right dorsolateral prefrontal cortex (Brodmann''s area 46). The ERD level in the right dorsolateral prefrontal cortex was positively associated with that in the sensorimotor areas within the time window of 500 to 700 ms. These results suggest that the right dorsolateral prefrontal cortex is involved in the neural substrates of the facilitation system and activates the sensorimotor areas during physical fatigue.     

Changes in the matching of somato-autonomic rhythms in the human operator during learning]

In subjects during the 1st through 15th day of training of the assemble job, before and during the work, the changes of concordance between the heart rate and respiration rhythm were studied in comparison with the dynamics of the activity results and of psychophysiological characteristics. In subjects with bad results of learning higher indices of respiratory-cardiac concordance and tremor were initially observed, what may serve as a criterion for professional selection for this kind of activity. In well learning subjects during transition from rest to work the initial desynchronization of somato-vegetative rhythms ("stress" type of reaction) was changed by an increase of their concordance. The relation of the training success to the type of working capacity of the subject ("morning", "evening") was also revealed.     

EEG study of the anxiolytic effect of scopolamine

Effect of the central M-cholinolytic scopolamine on spatial organization of the rat brain electrical activity was studied under conditions of high and low emotional-stress responses. The EEG changes were estimated by 840 parameters. A possibility of the EEG discrimination by means of interstrain differences in responses to scopolamine, was shown. A more obvious decrease in spectral power and potentials coherence was revealed in Maudsley Reactive rats (MR) as compared with the Maudsley Nonreactive rats (MNRA), in parieto-temporal and occipital areas of the right hemisphere, and the reverse interrelationship occurred in the anterior parts of the right and posterior parts of the left hemisphere. These findings suggest some specifics in the spatial distribution of the maximum scopolamine action foci depending on the initial emotional level. Changes occurring under the scopolamine effect in different EEG frequency bands are different in the MR and the MNRA rats. The findings are discussed in respect to the EEG indices of anxiolytic component of cholinergic regulation of the brain activity.     

Interhemispheric functional differences in prefrontal cortex of monkeys

Monkeys had nonpolarizable electrodes implanted bilaterally in prefrontal (principal sulcus), precentral, and occipital cortex. They were trained on a spatial delayed-response (DR) task (8-sec intratrial delay), while cortical potentials were recorded. Three groups of monkeys were trained to 90% criterion: (A) 4 monkeys with only the right hand (the left wrist was attached to the testing chair); (B) 2 monkeys with only the left hand; and (C) 2 monkeys with the left and right hands on alternate sessions. Intermanual transfer tests were then given. Averaged steady potential (SP) shifts of several seconds duration were found in prefrontal cortex during cue presentation and the early portion of the intratrial delay and from the precentral area during the choice response. Evaluations of these SP shift magnitudes indicated: (1) Training with only one hand resulted in substantially larger SP shifts in the prefrontal and precentral areas contralateral to the responding hand; (2) alternate hand training resulted in somewhat larger prefrontal SP shifts in the right hemisphere; (3) intermanual transfer had marked effects on the precentral SP shifts, with larger magnitudes in the hemisphere contralateral to the responding hand, but had little effect on the magnitudes of both prefrontal SP shifts. (4) Subsequent training of Group C monkeys with only one hand resulted in greater SP shifts in the prefrontal area contralateral to the responding hand and in decreased SP shifts in the ipsilateral prefrontal area; and (5) additional intermanual transfer tests had no effects on SP shift magnitudes from both prefrontal areas. These findings indicate a dissociation in interhemispheric functions between the precentral and prefrontal cortical areas, with the former implicated in motor organization for the contralateral limb, and the latter in mediation of mnemonic processes, primarily in one hemisphere. This hemispheric specialization is affected by the hand-training procedure, but other endogenous or experiential factors may be involved.