Post-training load-related changes of auditory working memory: An EEG study

Working memory (WM) refers to the temporary retention and manipulation of information, and its capacity is highly susceptible to training. Yet, the neural mechanisms that allow for increased performance under demanding conditions are not fully understood. We expected that post-training efficiency in WM performance modulates neural processing during high load tasks. We tested this hypothesis, using electroencephalography (EEG) (N = 39), by comparing source space spectral power of healthy adults performing low and high load auditory WM tasks. Prior to the assessment, participants either underwent a modality-specific auditory WM training, or a modality-irrelevant tactile WM training, or were not trained (active control). After a modality-specific training participants showed higher behavioral performance, compared to the control. EEG data analysis revealed general effects of WM load, across all training groups, in the theta-, alpha-, and beta-frequency bands. With increased load theta-band power increased over frontal, and decreased over parietal areas. Centro-parietal alpha-band power and central beta-band power decreased with load. Interestingly, in the high load condition a tendency toward reduced beta-band power in the right medial temporal lobe was observed in the modality-specific WM training group compared to the modality-irrelevant and active control groups. Our finding that WM processing during the high load condition changed after modality-specific WM training, showing reduced beta-band activity in voice-selective regions, possibly indicates a more efficient maintenance of task-relevant stimuli. The general load effects suggest that WM performance at high load demands involves complementary mechanisms, combining a strengthening of task-relevant and a suppression of task-irrelevant processing

From rest to task

A primary goal of neuroscience research on psychiatric disorders such as schizophrenia is to enhance the current understanding of underlying biological mechanisms in order to develop novel interventions. Human brain functions are maintained through activity of large-scale brain networks. Accordingly, deficient perceptual and cognitive processing can be caused by failures of functional integration within networks, as reflected by the disconnection hypothesis of schizophrenia. Various neuroimaging techniques can be applied to study functional brain networks, each having different strengths. Frequently used complementary methods are the electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), which were shown to have a common basis. Given the feasibility of combined EEG and fMRI measurement, EEG signatures of functional networks have been described, providing complimentary information about the functional state of networks. Both at rest and during task completion, many independent EEG and fMRI studies confirmed deficient network connectivity in schizophrenia. However, a rather diffuse picture with hyper- and hypo- activations within and between specific networks was reported. Furthermore, the theory of state dependent information processing argues that spontaneous and prestimulus brain activity interacts with upcoming task-related processes. Consequently, observed network deficits that vary according to task conditions could be caused by differences in resting or prestimulus state in schizophrenia. Based on that background, the present thesis aimed to increase the understanding of aberrant functional networks in schizophrenia by using simultaneous EEG-fMRI under different conditions. One study investigated integrative mechanisms of networks during eyes-open (EO) resting state using a common-phase synchronization measure in an EEG-informed fMRI analysis (study 3). The other two studies (studies 1&2) used an fMRI-informed EEG analysis: The second study was an extension of the first, which was performed in healthy subjects only. Hence, the same methodologies and analyses were applied in both studies, but in the second study schizophrenia patients were compared to healthy controls. The associations between four temporally coherent networks (TCNs) – the default mode network (DMN), the dorsal attention network (dAN), left and right working memory networks (WMNs) – and power of three EEG frequency bands (theta, alpha, and beta band) during a verbal working memory (WM) task were investigated. Both resting state and task-related studies performed in schizophrenia patients (studies 2&3) revealed altered activation strength, functional states and interaction of TCNs, especially of the DMN. During rest (study 3), the DMN was differently integrated through common-phase synchronization in the delta (0.5 – 3.5Hz) and beta (13 – 30Hz) band. At prestimulus states of a verbal WM task, however, study 2 did not reveal differences in the activation level of the DMN between groups. Furthermore, from pre-to-post stimulus, the association of the DMN with frontal-midline (FM) theta (3 – 7Hz) band was altered, and a reduced suppression of the DMN during WM retention was detected. Schizophrenia patients also demonstrated abnormal interactions between networks: the DMN and dAN showed a reduced anti-correlation and the WMNs demonstrated an absent lateralization effect (study 2). The view that schizophrenia patients display TCN deficiencies is supported by the results of the present thesis. Especially the DMN and its interaction to the task-positive dAN showed specific alterations at different mental states and their interaction (during rest and from pre-to-post stimulus). Those alterations might at least partly explain observed symptomatology as attentional orientation deficits in patients. To conclude, functional networks as the DMN might represent promising targets for novel treatment options such as neurofeedback or transcranial direct current stimulation (tDCS)

Brain Rhythms and Working Memory in Healthy Ageing

Working memory (WM), the ability to maintain and manipulate information to guide immediate cognitive processing, is vulnerable to age-related decline. Compared with younger adults, older adults demonstrate smaller WM capacities, a decrease in the ability to manipulate items held in WM, and a greater susceptibility to interference from distracting information. However, the neural underpinnings of WM decline in normal ageing are unclear. One technique that can be used to investigate the neurophysiological processes underlying cognition is electroencephalography (EEG), which non-invasively records activity from the awake human brain. The research described in this thesis uses EEG to investigate the neurophysiology of WM in healthy younger and older adults, with a particular focus on neural oscillatory activity in the alpha frequency range (8-12 Hz). As such, Chapter 1 consists of a review of the literature relevant to use of EEG to investigate the neurophysiology of WM performance in younger and older adults. WM performance deficits in older adults are particularly salient under increasing WM loads. Alpha oscillations have been shown to support verbal WM performance under high loads in younger adults, so the aim of Chapter 2 was to investigate the load-dependent modulation of alpha oscillatory power and frequency in younger and older adults during verbal WM. No age differences in verbal WM performance were found, and alpha power and alpha peak frequency were modulated in a similar task- and load-dependent manner in both younger and older adults. Another factor influencing WM performance in older adults is a decline in selective attention. Older adults perform worse on and are less able to modulate alpha power than younger adults in tasks involving cues about ‘where’ or ‘when’ a memory set will appear. The study described in Chapter 3 investigated whether providing cues towards memory set presentation time led to enhanced selective attention before the onset of the memory set, as indexed by alpha oscillatory activity. Predictive cues led to improved WM performance in both age groups, but alpha power in preparation of the memory set did not influence task performance. In Chapter 3, there were no age differences in WM performance when manipulating memory set presentation time. However, processing speed may not only limit the speed at which items are encoded into WM, but also the speed at which stimuli are transformed into a stable memory representation (i.e., WM consolidation). Therefore, the study contained in Chapter 4 investigated age differences in the ability to consolidate items into visual WM. In this study, older adults demonstrated poorer WM performance and slower consolidation at low WM loads, providing evidence for altered visual WM consolidation with age. Finally, visual WM is severely limited in capacity, highlighting the importance of encoding task-relevant information while ignoring distractors. The modulation of alpha oscillatory power has been implicated in the inhibition of distractors during WM in younger adults, but it is unclear if alpha power modulation also supports distractor inhibition in older adults. The study described in Chapter 5 investigated age differences in alpha oscillatory power before the onset of distractors during the visual WM retention period. Although there were no age differences in WM performance, younger adults demonstrated functionally relevant increases in alpha power before distractors, while older adults showed decreases in alpha power. Therefore, younger and older adults likely use different neural strategies to inhibit distractors during WM performance. Taken together, the results of the studies contained in this thesis provide further evidence for age-related changes to neural oscillatory activity, particularly in the alpha frequency band, even when age differences in WM performance are not present. These findings may have important implications for providing novel targets for detecting or preventing age-related cognitive decline.Thesis (Ph.D.) -- University of Adelaide, School of Biomedicine, 202

For whom the bell tolls : periodic reactivation of sensory cortex in the gamma band as a substrate of visual working memory maintenance

Peer reviewedPublisher PD

Exploring intermediate phenotypes with EEG: Working memory dysfunction in schizophrenia

This review brings together two strands of investigation in the neuropsychology and neurophysiology of schizophrenia that have been particularly productive over the last 20 years. We review the literature on working memory deficits, particularly in the visual domain, and changes in oscillatory neural activity as measured with electroencephalography (EEG) and magnetoencephalography (MEG). We argue that recent results suggest a link between these two phenomena, in that altered oscillations underlie some of the working memory deficits. We furthermore argue that early sensory mechanisms contribute more to working memory (and other) deficits than previously thought. The final part of our review suggests links between working memory, oscillations, and their alterations in schizophrenia and the dopamine, GABA, glutamate and acetylcholine system. These links have already resulted in the development of new remediation strategies, which have some translational potential

Linking topiramate exposure to changes in electrophysiological activity and behavioral deficits through quantitative pharmacological modeling

University of Minnesota Ph.D. dissertation. May 2019. Major: Experimental & Clinical Pharmacology. Advisors: Susan Marino, Angela Birnbaum. 1 computer file (PDF); xv, 166 pages.Topiramate is a broad-spectrum anti-epileptic drug used to treat a variety of conditions, including epilepsy, migraine, substance abuse, mood, and eating disorders. We investigated the effects of topiramate on the working memory system using population pharmacokinetic-pharmacodynamic modeling and unsupervised machine learning approaches. Working memory is the capacity-limited neurocognitive system responsible for simultaneous maintenance and manipulation of information in order to achieve a goal. Behavioral and electrophysiological indices of working memory function were measured using data collected during a double-blind, placebo-controlled crossover study in healthy volunteers. Subjects completed a Sternberg working memory task, during which accuracy and reaction time were measured, while subjects’ EEG was recorded. A pharmacokinetic-pharmacodynamic model was constructed which demonstrated that accuracy decreased linearly as a function of plasma concentration, and that the magnitude of individual deficits was predicted by working memory capacity. A separate pharmacokinetic-pharmacodynamic model was developed which showed that spectral power in the theta frequency band (4-8 Hz) recorded during the retention phase of the Sternberg task increased as a function of plasma concentration. Furthermore, a mixture model identified two subpopulations with differential sensitivity in topiramate-induced theta reactivity. In the subpopulation defined by lower reactivity, reaction times were 20% slower than in the high theta reactivity subpopulation. Principal component regression was used to quantify the relationship between changes in multiple measures of electrophysiological activity and behavioral deficits. Theta power during retention was found to be the best predictor of topiramate-related behavioral deficits. Performance on another working memory task, Digit Span Forward, was also predicted by theta power during retention, as well as alpha (8-12 Hz) power during encoding and retrieval stages. In conclusion, two treatment-independent factors that predict differences in behavioral and electrophysiological responses to topiramate administration were identified: working memory capacity and theta reactivity. Future research will be needed to determine the utility of these demographic factors in predicting risk of cognitive side effects in patients eligible for treatment with topiramate

The Effects of Neurocognitive Aging on Sentence Processing

Across the lifespan, successful language comprehension is crucial for continued participation in everyday life. The success of language comprehension relies on the intact functioning of both language-specific processes as well as domain-general cognitive processes that support language comprehension in general. This two-sided nature of successful language comprehension may contribute to the two diverging observations in healthy aging: the preservation and the decline of language comprehension on both the cognitive and the neural level. To date, our understanding of these two competing facets is incomplete and unclear. While greater language experience comes with increasing age, most domain-general cognitive functions, like verbal working memory, decline in healthy aging. The here presented thesis shows that when the electrophysiological network relevant for verbal working memory is already compromised at rest, language comprehension declines in older adults. Moreover, it could be shown that, as verbal working memory capacity declines with age, resources may be- come insufficient to successfully encode language-specific information into memory, yielding language comprehension difficulties in old age. Age differences in the electrophysiological dynamics underlying sentence encoding indicate that the encoding of detailed information may increasingly be inhibited throughout the lifespan, possibly to avoid overloading the verbal working memory. However, limitations in verbal working memory could be attenuated by the use of language-specific constraints. That is, semantic and syntactic constraints can be used to establish relations between words which reduces the memory load from individual word information to information about word group. Here, it was found that older adults do not benefit from the use of syntactic constraints as much as younger adults while the benefit of using semantic constraints was comparable across age. Overall, the here presented thesis suggests that previous findings on language comprehension in healthy aging are not contradictory but rather converge on a simultaneous combination of selective preservation and decline of various language-specific processes, burdened by domain-general neurocognitive aging

Temporally Distinct Oscillatory Codes of Retention and Manipulation of Verbal Working Memory

Most psychophysiological studies of working memory (WM) target only the short-term memory construct, whereas short-term memory is only a part of the WM responsible for the storage of sensory information. Here, we aimed to further investigate oscillatory brain mechanisms supporting the executive components of WM—the part responsible for the manipulation of information. We conducted an exploratory reanalysis of a previously published EEG dataset where 156 participants (82 females) performed tasks requiring either simple retention or retention and manipulation of verbal information in WM. A relatively long delay period (>6 s) was employed to investigate the temporal trajectory of the oscillatory brain activity. Compared with baseline, theta activity was significantly enhanced during encoding and the delay period. Alpha-band power decreased during encoding and switched to an increase in the first part of the delay before returning to the baseline in the second part; beta-band power remained below baseline during encoding and the delay. The difference between the manipulation and retention tasks in spectral power had diverse temporal trajectories in different frequency bands. The difference maintained over encoding and the first part of the delay in theta, during the first part of the delay in beta, and during the whole delay period in alpha. Our results suggest that task-related modulations in theta power co-vary with the demands on the executive control network; beta suppression during mental manipulation can be related to the activation of motor networks; and alpha is likely to reflect the activation of language areas simultaneously with sensory input blockade. © 2021 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.Study was supported by Russian Foundation for Basic Research (RFBR) №19‐013‐00027

The Effect of Binaural Beats on Visuospatial Working Memory and Cortical Connectivity

Binaural beats utilize a phenomenon that occurs within the cortex when two different frequencies are presented separately to each ear. This procedure produces a third phantom binaural beat, whose frequency is equal to the difference of the two presented tones and which can be manipulated for non-invasive brain stimulation. The effects of binaural beats on working memory, the system in control of temporary retention and online organization of thoughts for successful goal directed behavior, have not been well studied. Furthermore, no studies have evaluated the effects of binaural beats on brain connectivity during working memory tasks. In this study, we determined the effects of different acoustic stimulation conditions on participant response accuracy and cortical network topology, as measured by EEG recordings, during a visuospatial working memory task. Three acoustic stimulation control conditions and three binaural beat stimulation conditions were used: None, Pure Tone, Classical Music, 5Hz binaural beats, 10Hz binaural beats, and 15Hz binaural beats. We found that listening to 15Hz binaural beats during a visuospatial working memory task not only increased the response accuracy, but also modified the strengths of the cortical networks during the task. The three auditory control conditions and the 5Hz and 10Hz binaural beats all decreased accuracy. Based on graphical network analyses, the cortical activity during 15Hz binaural beats produced networks characteristic of high information transfer with consistent connection strengths throughout the visuospatial working memory task