Oscillations in the prefrontal cortex: a gateway to memory and attention

We consider the potential role of oscillations in the prefrontal cortex (PFC) in mediating attention, working memory and memory consolidation. Activity in the theta, beta, and gamma bands is related to communication between PFC and different brain areas. While gamma/beta oscillations mediate bottom-up and top-down interactions between PFC and visual cortices, related to attention, theta rhythms are engaged by hippocampal/PFC interplay. These interactions are dynamic, depending on the nature and relevance of the information currently being processed. The profound modifications of the PFC neuronal network associated with changes in oscillatory coherence are controlled by neuromodulators such as dopamine, which thereby allow or prevent the formation of cell assemblies for information encoding and storage.     

Changes in the cortical electric activity in the course of set formation under conditions of increased loading of the working memory

Stability of the cognitive set to nonsense words in healthy adult subjects was compared in two experimental conditions: (1) subjects had only to recognize pseudowords/words; (2) in each trial after the pseudoword/word recognition, subjects had to press a button in response to a visual probe stimulus and only after this action to pronounce a recognized pseudoword/word. It was shown that complication of the cognitive performance in the second condition did not affect the set rigidity. However, the pattern of the cortical electric activity substantially changed: the EEG power in the theta frequency range and coherence function, in particular, interhemispheric, in the frontal cortical areas were higher in the second condition. The increase in coherence function in the frontal areas was most pronounced in the theta and alphal ranges. It was suggested that increase in activity of the frontal regions of the brain cortex facilitates shifts of visual sets under increasing load of the working memory.     

Arbitrary symbolism in natural language revisited: when word forms carry meaning

Cognitive science has a rich history of interest in the ways that languages represent abstract and concrete concepts (e.g., idea vs. dog). Until recently, this focus has centered largely on aspects of word meaning and semantic representation. However, recent corpora analyses have demonstrated that abstract and concrete words are also marked by phonological, orthographic, and morphological differences. These regularities in sound-meaning correspondence potentially allow listeners to infer certain aspects of semantics directly from word form. We investigated this relationship between form and meaning in a series of four experiments. In Experiments 1-2 we examined the role of metalinguistic knowledge in semantic decision by asking participants to make semantic judgments for aurally presented nonwords selectively varied by specific acoustic and phonetic parameters. Participants consistently associated increased word length and diminished wordlikeness with abstract concepts. In Experiment 3, participants completed a semantic decision task (i.e., abstract or concrete) for real words varied by length and concreteness. Participants were more likely to misclassify longer, inflected words (e.g., "apartment") as abstract and shorter uninflected abstract words (e.g., "fate") as concrete. In Experiment 4, we used a multiple regression to predict trial level naming data from a large corpus of nouns which revealed significant interaction effects between concreteness and word form. Together these results provide converging evidence for the hypothesis that listeners map sound to meaning through a non-arbitrary process using prior knowledge about statistical regularities in the surface forms of words.     

Right Inferior Frontal Gyrus Activation Is Associated with Memory Improvement in Patients with Left Frontal Low-Grade Glioma Resection

Patients with low-grade glioma (LGG) have been studied as a model of functional brain reorganization due to their slow-growing nature. However, there is no information regarding which brain areas are involved during verbal memory encoding after extensive left frontal LGG resection. In addition, it remains unknown whether these patients can improve their memory performance after instructions to apply efficient strategies. The neural correlates of verbal memory encoding were investigated in patients who had undergone extensive left frontal lobe (LFL) LGG resections and healthy controls using fMRI both before and after directed instructions were given for semantic organizational strategies. Participants were scanned during the encoding of word lists under three different conditions before and after a brief period of practice. The conditions included semantically unrelated (UR), related-non-structured (RNS), and related-structured words (RS), allowing for different levels of semantic organization. All participants improved on memory recall and semantic strategy application after the instructions for the RNS condition. Healthy subjects showed increased activation in the left inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during encoding for the RNS condition after the instructions. Patients with LFL excisions demonstrated increased activation in the right IFG for the RNS condition after instructions were given for the semantic strategies. Despite extensive damage in relevant areas that support verbal memory encoding and semantic strategy applications, patients that had undergone resections for LFL tumor could recruit the right-sided contralateral homologous areas after instructions were given and semantic strategies were practiced. These results provide insights into changes in brain activation areas typically implicated in verbal memory encoding and semantic processing.     

Learning in trance: Functional brain imaging studies and neuropsychology

This study examined the fundamental question, whether verbal memory processing in hypnosis and in the waking state is mediated by a common neural system or by distinct cortical areas. Seven right-handed volunteers (25.4 years, sd 3.1) with high-hypnotic susceptibility scores were PET-scanned while encoding/retrieving word associations either in hypnosis or in the waking state. Word-pairs were visually presented and highly imaginable, but not semantically related (e.g. monkey-street). The presentation of pseudo-words served as a reference condition. An emission scan was recorded after each intravenous administration of O-15 water. Encoding under hypnosis was associated with more pronounced bilateral activations in the occipital cortex and the prefrontal areas as compared to learning in the waking state. During memory retrieval of word-pairs which had been previously learned under hypnosis, activations were found in the occipital lobe and the cerebellum. Under both experimental conditions precuneus and prefrontal cortex showed a consistent bilateral activation which was most distinct when the learning had taken place under hypnosis. In order to further analyze the effect of hypnosis on imagery-mediated learning, we administered sets of high-imagery word-pairs and sets of abstract words. In the first experimental condition word-pair associations were presented visually. In the second condition it was found that highly hypnotisable persons recalled significantly more high-imagery words under hypnosis as compared to low-hypnotisables both in the visual and auditory modality. Furthermore, high-imagery words were also better recalled by the highly hypnotisable subjects during the non-hypnotic condition. The memory effect was consistently present under both, immediate and delayed recall conditions. Taken together, the findings advance our understanding of the neural representation that underlies hypnosis and the neuropsychological correlates of hypnotic susceptibility.     

Emotional Picture and Word Processing: An fMRI Study on Effects of Stimulus Complexity

Neuroscientific investigations regarding aspects of emotional experiences usually focus on one stimulus modality (e.g., pictorial or verbal). Similarities and differences in the processing between the different modalities have rarely been studied directly. The comparison of verbal and pictorial emotional stimuli often reveals a processing advantage of emotional pictures in terms of larger or more pronounced emotion effects evoked by pictorial stimuli. In this study, we examined whether this picture advantage refers to general processing differences or whether it might partly be attributed to differences in visual complexity between pictures and words. We first developed a new stimulus database comprising valence and arousal ratings for more than 200 concrete objects representable in different modalities including different levels of complexity: words, phrases, pictograms, and photographs. Using fMRI we then studied the neural correlates of the processing of these emotional stimuli in a valence judgment task, in which the stimulus material was controlled for differences in emotional arousal. No superiority for the pictorial stimuli was found in terms of emotional information processing with differences between modalities being revealed mainly in perceptual processing regions. While visual complexity might partly account for previously found differences in emotional stimulus processing, the main existing processing differences are probably due to enhanced processing in modality specific perceptual regions. We would suggest that both pictures and words elicit emotional responses with no general superiority for either stimulus modality, while emotional responses to pictures are modulated by perceptual stimulus features, such as picture complexity.     

Cortical functional connectivity during the retention of affective pictures in working memory: EEG-source theta coherence analysis

The pattern of cortical functional connectivity in the source space was studied in a group of righthanded adult participants (N = 44:17 women, 27 men, aged M = 29.61 ± 6.45 years). Participants retained the traces of realistic pictures of positive, neutral, and negative emotional valences in their working memory (WM) while performing the same-different task. Within the framework of this task, participants had to compare the initial picture against a target picture that followed after a specified delay. The coherence (COH) between the pairs of cortical sources chosen in advance according to fMRI data was estimated in the theta frequency range for the period preceding the initial stimulus, during the retention of the initial stimulus in WM, and during the rest interval between successive trials. Two distinct sets of functional links were found. The links of the first type that presumably reflected the involvement of sustained attention were between the dorsal anterior cingulate cortex, the prefrontal areas, and temporal areas of the right hemispheres. When compared to the rest period, the links of this type showed strengthening not only during the retention period but also during the period preceding the initial picture. The links of the second type presumably reflected a progressive neocortex-to-hippocampus functional integration with increasing memory load and strengthened exclusively during the retention period. These links were between the parietal, temporal and prefrontal cortices in the lateral surface of both hemispheres with the additional inclusion of the posterior cingulate cortex and the medial parietal cortex in the left hemisphere. The impact of emotional valence on the strength and topography of the functional links of the second type was found. In the left hemisphere, the increase of strength of cortical interaction was more pronounced for the pictures of positive valence than for the pictures of either neutral or negative valences. When compared to the pictures of neutral valence, the retention of pictorial information of both positive and negative valence showed some extraneous integration of the cortical areas for the theta rhythm. This finding might be related to the additional load exerted by emotionally colored pictures onto the mechanisms of short-time retention of visual information.     

Phase locking of single neuron activity to theta oscillations during working memory in monkey extrastriate visual cortex

Working memory has been linked to elevated single neuron discharge in monkeys and to oscillatory changes in the human EEG, but the relation between these effects has remained largely unexplored. We addressed this question by measuring local field potentials and single unit activity simultaneously from multiple electrodes placed in extrastriate visual cortex while monkeys were performing a working memory task. We describe a significant enhancement in theta band energy during the delay period. Theta oscillations had a systematic effect on single neuron activity, with neurons emitting more action potentials near their preferred angle of each theta cycle. Sample-selective delay activity was enhanced if only action potentials emitted near the preferred theta angle were considered. Our results suggest that extrastriate visual cortex is involved in short-term maintenance of information and that theta oscillations provide a mechanism for structuring the recurrent interaction between neurons in different brain regions that underlie working memory.     

Reward-related FMRI activation of dopaminergic midbrain is associated with enhanced hippocampus-dependent long-term memory formation

Long-term potentiation in the hippocampus can be enhanced and prolonged by dopaminergic inputs from midbrain structures such as the substantia nigra. This improved synaptic plasticity is hypothesized to be associated with better memory consolidation in the hippocampus. We used a condition that reliably elicits a dopaminergic response, reward anticipation, to study the relationship between activity of dopaminergic midbrain areas and hippocampal long-term memory in healthy adults. Pictures of object drawings that predicted monetary reward were associated with stronger fMRI activity in reward-related brain areas, including the substantia nigra, compared with non-reward-predicting pictures. Three weeks later, recollection and source memory were better for reward-predicting than for non-reward-predicting pictures. FMRI activity in the hippocampus and the midbrain was higher for reward-predicting pictures that were later recognized compared with later forgotten pictures. These data are consistent with the hypothesis that activation of dopaminergic midbrain regions enhances hippocampus-dependent memory formation, possibly by enhancing consolidation.     

Movement-related theta rhythm in humans: coordinating self-directed hippocampal learning

The hippocampus is crucial for episodic or declarative memory and the theta rhythm has been implicated in mnemonic processing, but the functional contribution of theta to memory remains the subject of intense speculation. Recent evidence suggests that the hippocampus might function as a network hub for volitional learning. In contrast to human experiments, electrophysiological recordings in the hippocampus of behaving rodents are dominated by theta oscillations reflecting volitional movement, which has been linked to spatial exploration and encoding. This literature makes the surprising cross-species prediction that the human hippocampal theta rhythm supports memory by coordinating exploratory movements in the service of self-directed learning. We examined the links between theta, spatial exploration, and memory encoding by designing an interactive human spatial navigation paradigm combined with multimodal neuroimaging. We used both non-invasive whole-head Magnetoencephalography (MEG) to look at theta oscillations and Functional Magnetic Resonance Imaging (fMRI) to look at brain regions associated with volitional movement and learning. We found that theta power increases during the self-initiation of virtual movement, additionally correlating with subsequent memory performance and environmental familiarity. Performance-related hippocampal theta increases were observed during a static pre-navigation retrieval phase, where planning for subsequent navigation occurred. Furthermore, periods of the task showing movement-related theta increases showed decreased fMRI activity in the parahippocampus and increased activity in the hippocampus and other brain regions that strikingly overlap with the previously observed volitional learning network (the reverse pattern was seen for stationary periods). These fMRI changes also correlated with participant's performance. Our findings suggest that the human hippocampal theta rhythm supports memory by coordinating exploratory movements in the service of self-directed learning. These findings directly extend the role of the hippocampus in spatial exploration in rodents to human memory and self-directed learning.     

Neural dynamics of the cognitive map in the hippocampus

The rodent hippocampus has been thought to represent the spatial environment as a cognitive map. In the classical theory, the cognitive map has been explained as a consequence of the fact that different spatial regions are assigned to different cell populations in the framework of rate coding. Recently, the relation between place cell firing and local field oscillation theta in terms of theta phase precession was experimentally discovered and suggested as a temporal coding mechanism leading to memory formation of behavioral sequences accompanied with asymmetric Hebbian plasticity. The cognitive map theory is apparently outside of the sequence memory view. Therefore, theoretical analysis is necessary to consider the biological neural dynamics for the sequence encoding of the memory of behavioral sequences, providing the cognitive map formation. In this article, we summarize the theoretical neural dynamics of the real-time sequence encoding by theta phase precession, called theta phase coding, and review a series of theoretical models with the theta phase coding that we previously reported. With respect to memory encoding functions, instantaneous memory formation of one-time experience was first demonstrated, and then the ability of integration of memories of behavioral sequences into a network of the cognitive map was shown. In terms of memory retrieval functions, theta phase coding enables the hippocampus to represent the spatial location in the current behavioral context even with ambiguous sensory input when multiple sequences were coded. Finally, for utilization, retrieved temporal sequences in the hippocampus can be available for action selection, through the process of reverting theta rhythm-dependent activities to information in the behavioral time scale. This theoretical approach allows us to investigate how the behavioral sequences are encoded, updated, retrieved and used in the hippocampus, as the real-time interaction with the external environment. It may indeed be the bridge to the episodic memory function in human hippocampus.     

Learning related interactions among neuronal systems involved in memory processes

Functional neuroimaging techniques using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have provided new insights in our understanding of brain function from the molecular to the systems level. While subtraction strategy based data analyses have revealed the involvement of distributed brain regions in memory processes, covariance analysis based data analysis strategies allow functional interactions between brain regions of a neuronal network to be assessed. The focus of this chapter is to (1) establish the functional topography of episodic and working memory processes in young and old normal volunteers, (2) to assess functional interactions between modules of networks of brain regions by means of covariance based analyses and systems level modelling and (3) to relate neuroimaging data to the underpinning neural networks. Male normal young and old volunteers without neurological or psychiatric illness participated in neuroimaging studies (PET, fMRI) on working and episodic memory. Distributed brain areas are involved in memory processes (episodic and working memory) in young volunteers and show much of an overlap with respect to the network components. Systems level modelling analyses support the hypothesis of bihemispheric, asymmetric networks subserving memory processes and revealed both similarities in general and differences in the interactions between brain regions during episodic encoding and retrieval as well as working memory. Changes in memory function with ageing are evident from studies in old volunteers activating more brain regions compared to young volunteers and revealing more and stronger influences of prefrontal regions. We finally discuss the way in which the systems level models based on PET and fMRI results have implications for the understanding of the underlying neural network functioning of the brain.     

Electrophysiological bases of semantic processing of objects

How pictures and words are stored and processed in the human brain constitute a long-standing question in cognitive psychology. Behavioral studies have yielded a large amount of data addressing this issue. Generally speaking, these data show that there are some interactions between the semantic processing of pictures and words. However, behavioral methods can provide only limited insight into certain findings. Fortunately, Event-Related Potential (ERP) provides on-line cues about the temporal nature of cognitive processes and contributes to the exploration of their neural substrates. ERPs have been used in order to better understand semantic processing of words and pictures. The main objective of this article is to offer an overview of the electrophysiologic bases of semantic processing of words and pictures. Studies presented in this article showed that the processing of words is associated with an N 400 component, whereas pictures elicited both N 300 and N 400 components. Topographical analysis of the N 400 distribution over the scalp is compatible with the idea that both image-mediated concrete words and pictures access an amodal semantic system. However, given the distinctive N 300 patterns, observed only during picture processing, it appears that picture and word processing rely upon distinct neuronal networks, even if they end up activating more or less similar semantic representations.     

The Influence of a Working Memory Task on Affective Perception of Facial Expressions

In a dual-task paradigm, participants performed a spatial location working memory task and a forced two-choice perceptual decision task (neutral vs. fearful) with gradually morphed emotional faces (neutral ∼ fearful). Task-irrelevant word distractors (negative, neutral, and control) were experimentally manipulated during spatial working memory encoding. We hypothesized that, if affective perception is influenced by concurrent cognitive load using a working memory task, task-irrelevant emotional distractors would bias subsequent perceptual decision-making on ambiguous facial expression. We found that when either neutral or negative emotional words were presented as task-irrelevant working-memory distractors, participants more frequently reported fearful face perception - but only at the higher emotional intensity levels of morphed faces. Also, the affective perception bias due to negative emotional distractors correlated with a decrease in working memory performance. Taken together, our findings suggest that concurrent working memory load by task-irrelevant distractors has an impact on affective perception of facial expressions.     

Arithmetic Memory Is Modality Specific

In regards to numerical cognition and working memory, it is an open question as to whether numbers are stored into and retrieved from a central abstract representation or from separate notation-specific representations. This study seeks to help answer this by utilizing the numeral modality effect (NME) in three experiments to explore how numbers are processed by the human brain. The participants were presented with numbers (1–9) as either Arabic digits or written number words (Arabic digits and dot matrices in Experiment 2) at the first (S1) and second (S2) stimuli. The participant’s task was to add the first two stimuli together and verify whether the answer (S3), presented simultaneously with S2, was correct. We hypothesized that if reaction time (RT) at S2/S3 depends on the modality of S1 then numbers are retrieved from modality specific memory stores. Indeed, RT depended on the modality of S1 whenever S2 was an Arabic digit which argues against the concept of numbers being stored and retrieved from a central, abstract representation.     

Influence of neuroendocrine shifts in the pubertal period on the working memory operation in adolescents

It was found that the volume of working memory in adolescents at the initial pubertal stages (II–III) was lower than in adults. Analysis of the event-related potentials (ERPs) in various cortical areas in adolescents when they compared two successive pictures revealed specific features of neurophysiological mechanisms of visual working memory at the early pubertal stages. As compared to adult subjects, the adolescents were characterized by longer latencies and higher amplitudes of the early components of the ERPs. Certain differences were revealed in the functional organization of working memory both at the stages of stimulus fixation and in its comparison with the current information.     

Gender differences in EEG coherence during memorization of dichotically and monaurally presented verbal stimuli

Gender differences in changes of coherence values in the theta and alpha frequency bands during encoding of dichotically and monaurally presented verbal information were studied. Right-handed students (14 male and 14 female subjects) participated in experiments. The EEG was recorded from 16 electrodes placed at homologous sites of the left and the right hemispheres. In male subjects, numerous differences in coherence values between conditions of dichotical and monaural word presentation were found in the theta2- and alpha1-bands, in females, the differences were most pronounced in the theta1- and theta2-frequency bands. Numerous differences in coherence values differentiated between dichotic and left-sided monaural presentations in males and between dichotic and right-sided monaural presentations in females. As compared to dichotic presentation, in condition of the monaural presentation, higher coherence values were observed in men and lower in women. The features of gender differences in frequency-spatial patterns of changes in EEG coherence values under conditions of bilaterally and unilaterally directed attention in male and female groups may testify that female subjects predominantly use right-hemispheric processing strategy, whereas male subjects use, mainly, left-hemispheric strategy for selection and memorization of concrete nouns.     

Explore the Functional Connectivity between Brain Regions during a Chemistry Working Memory Task

Previous studies have rarely examined how temporal dynamic patterns, event-related coherence, and phase-locking are related to each other. This study assessed reaction-time-sorted spectral perturbation and event-related spectral perturbation in order to examine the temporal dynamic patterns in the frontal midline (F), central parietal (CP), and occipital (O) regions during a chemistry working memory task at theta, alpha, and beta frequencies. Furthermore, the functional connectivity between F-CP, CP-O, and F-O were assessed by component event-related coherence (ERCoh) and component phase-locking (PL) at different frequency bands. In addition, this study examined whether the temporal dynamic patterns are consistent with the functional connectivity patterns across different frequencies and time courses. Component ERCoh/PL measured the interactions between different independent components decomposed from the scalp EEG, mixtures of time courses of activities arising from different brain, and artifactual sources. The results indicate that the O and CP regions’ temporal dynamic patterns are similar to each other. Furthermore, pronounced component ERCoh/PL patterns were found to exist between the O and CP regions across each stimulus and probe presentation, in both theta and alpha frequencies. The consistent theta component ERCoh/PL between the F and O regions was found at the first stimulus and after probe presentation. These findings demonstrate that temporal dynamic patterns at different regions are in accordance with the functional connectivity patterns. Such coordinated and robust EEG temporal dynamics and component ERCoh/PL patterns suggest that these brain regions’ neurons work together both to induce similar event-related spectral perturbation and to synchronize or desynchronize simultaneously in order to swiftly accomplish a particular goal. The possible mechanisms for such distinct component phase-locking and coherence patterns were also further discussed.     

Theta returns

Recent physiological studies have implicated theta - a high-amplitude 4-8 Hz oscillation that is prominent in rat hippocampus during locomotion, orienting and other voluntary behaviors - in synaptic plasticity, information coding and the function of working memory. Intracranial recordings from human cortex have revealed evidence of high-amplitude theta oscillations throughout the brain, including the neocortex. Although its specific role is largely unknown, the observation of human theta has begun to reveal an intriguing connection between brain oscillations and cognitive processes.     

Cognitive Behavioral Performance of Untreated Depressed Patients with Mild Depressive Symptoms

This study evaluated the working memory performance of 18 patients experiencing their first onset of mild depression without treatment and 18 healthy matched controls. The results demonstrated that working memory impairment in patients with mild depression occurred when memorizing the position of a picture but not when memorizing the pictures themselves. There was no significant difference between the two groups in the emotional impact on the working memory, indicating that the attenuation of spatial working memory was not affected by negative emotion; however, cognitive control selectively affected spatial working memory. In addition, the accuracy of spatial working memory in the depressed patients was not significantly reduced, but the reaction time was significantly extended compared with the healthy controls. This finding indicated that there was no damage to memory encoding and function maintenance in the patients but rather only impaired memory retrieval, suggesting that the extent of damage to the working memory system and cognitive control abilities was associated with the corresponding depressive symptoms. The development of mild to severe depressive symptoms may be accompanied by spatial working memory damage from the impaired memory retrieval function extending to memory encoding and memory retention impairments. In addition, the impaired cognitive control began with an inadequate capacity to automatically process internal negative emotions and further extended to impairment of the ability to regulate and suppress external emotions. The results of the mood-congruent study showed that the memory of patients with mild symptoms of depression was associated with a mood-congruent memory effect, demonstrating that mood-congruent memory was a typical feature of depression, regardless of the severity of depression. This study provided important information for understanding the development of cognitive dysfunction.