Oscillatory Control over Representational States in Working Memory

In the visual world, attention is guided by perceptual goals activated in visual working memory (VWM). However, planning multiple-task sequences also requires VWM to store representations for future goals. These future goals need to be prevented from interfering with the current perceptual task. Recent findings have implicated neural oscillations as a control mechanism serving the implementation and switching of different states of prioritization of VWM representations. We review recent evidence that posterior alpha-band oscillations underlie the flexible activation and deactivation of VWM representations and that frontal delta-to-theta-band oscillations play a role in the executive control of this process. That is, frontal delta-to-theta appears to orchestrate posterior alpha through long-range oscillatory networks to flexibly set up and change VWM states during multitask sequences

Magnetoencephalography as a tool in psychiatric research: current status and perspective

The application of neuroimaging to provide mechanistic insights into circuit dysfunctions in major psychiatric conditions and the development of biomarkers are core challenges in current psychiatric research. In this review, we propose that recent technological and analytic advances in Magnetoencephalography (MEG), a technique which allows the measurement of neuronal events directly and non-invasively with millisecond resolution, provides novel opportunities to address these fundamental questions. Because of its potential in delineating normal and abnormal brain dynamics, we propose that MEG provides a crucial tool to advance our understanding of pathophysiological mechanisms of major neuropsychiatric conditions, such as Schizophrenia, Autism Spectrum Disorders, and the dementias. In our paper, we summarize the mechanisms underlying the generation of MEG signals and the tools available to reconstruct generators and underlying networks using advanced source-reconstruction techniques. We then survey recent studies that have utilized MEG to examine aberrant rhythmic activity in neuropsychiatric disorders. This is followed by links with preclinical research, which have highlighted possible neurobiological mechanisms, such as disturbances in excitation/inhibition parameters, which could account for measured changes in neural oscillations. In the final section of the paper, challenges as well as novel methodological developments are discussed which could pave the way for a widespread application of MEG in translational research with the aim of developing biomarkers for early detection and diagnosis

Transcranial alternating current stimulation (tACS) at 40 Hz enhances face and object perception

Neurophysiological evidence suggests that face and object recognition relies on the coordinated activity of neural populations (i.e., neural oscillations) in the gamma-band range (> 30 Hz) over the occipito-temporal cortex. To test the causal effect of gamma-band oscillations on face and object perception we applied transcranial Alternating Current Stimulation (tACS) in healthy volunteers (N = 60). In this single-blind, sham-controlled study, we examined whether the administration of offline tACS at gamma-frequency (40 Hz) over the right occipital cortex enhances performance of perception and memory of face and object stimuli. We hypothesized that gamma tACS would enhance the perception of both categories of visual stimuli. Results, in line with our hypothesis, show that 40 Hz tACS enhanced both face and object perception. This effect is process-specific (i.e., it does not affect memory), frequency-specific (i.e., stimulation at 5 Hz did not cause any behavioural change), and site-specific (i.e., stimulation of the sensory-motor cortex did not affect performance). Our findings show that high-frequency tACS modulates human visual perception, and it is in line with neurophysiological studies showing that the perception of visual stimuli (i.e., faces and objects) is mediated by oscillations in the gamma-band range. Furthermore, this study adds insight about the design of effective neuromodulation protocols that might have implications for interventions in clinical settings

Feature-Specific Information Processing Precedes Concerted Activation in Human Visual Cortex

Current knowledge about the precise timing of visual input to the cortex relies largely on spike timings in monkeys and evoked-response latencies in humans. However, quantifying the activation onset does not unambiguously describe the timing of stimulus-feature-specific information processing. Here, we investigated the information content of the early human visual cortical activity by decoding low-level visual features from single-trial magnetoencephalographic (MEG) responses. MEG was measured from nine healthy subjects as they viewed annular sinusoidal gratings (spanning the visual field from 2 to 10° for a duration of 1 s), characterized by spatial frequency (0.33 cycles/degree or 1.33 cycles/degree) and orientation (45° or 135°); gratings were either static or rotated clockwise or anticlockwise from 0 to 180°. Time-resolved classifiers using a 20 ms moving window exceeded chance level at 51 ms (the later edge of the window) for spatial frequency, 65 ms for orientation, and 98 ms for rotation direction. Decoding accuracies of spatial frequency and orientation peaked at 70 and 90 ms, respectively, coinciding with the peaks of the onset evoked responses. Within-subject time-insensitive pattern classifiers decoded spatial frequency and orientation simultaneously (mean accuracy 64%, chance 25%) and rotation direction (mean 82%, chance 50%). Classifiers trained on data from other subjects decoded the spatial frequency (73%), but not the orientation, nor the rotation direction. Our results indicate that unaveraged brain responses contain decodable information about low-level visual features already at the time of the earliest cortical evoked responses, and that representations of spatial frequency are highly robust across individuals.Peer reviewe

Neural Activity Is Dynamically Modulated by Memory Load During the Maintenance of Spatial Objects

Visuospatial working memory (WM) is a fundamental but severely limited ability to temporarily remember selected stimuli. Several studies have investigated the underlying neural mechanisms of maintaining various visuospatial stimuli simultaneously (i.e., WM load, the number of representations that need to be maintained in WM). However, two confounding factors, namely verbal representation and encoding load (the number of items that need to be encoded into WM), have not been well controlled in previous studies. In this study, we developed a novel delayed-match-to-sample task (DMST) controlling for these two confounding factors and recorded scalp EEG signals during the task. We found that behavioral performance deteriorated severely as memory load increased. Neural activity was modulated by WM load in a dynamic manner. Specifically, higher memory load induced stronger amplitude in occipital and central channel-clusters during the early delay period, while the inverse trend was observed in central and frontal channel-clusters during late delay. In addition, the same inverse memory load effect, that was lower memory load induced stronger amplitude, was observed in occipital channel-cluster alpha power during late delay. Finally, significant correlations between neural activity and individual reaction time showed a role of late-delay central and frontal channel-cluster amplitude in predicting behavioral performance. Because the occipital cortex is important for visual information maintenance, the decrease in alpha oscillation was consistent with the cognitive role that is “gating by inhibition.” Together, our results from a well-controlled DMST suggest that WM load not exerted constant but dynamic effect on neural activity during maintenance of visuospatial objects

Intraparietal sulcus maintains working memory representations of somatosensory categories in an adaptive, context-dependent manner

Working memory (WM) representations are generally known to be influenced by task demands, but it is not clear whether this extends to the somatosensory domain. One way to investigate the influence of task demands is with categorization paradigms, wherein either a single stimulus or an associated category is maintained in WM. In the somatosensory modality, category representations have been identified in the premotor cortex (PMC) and the intraparietal sulcus (IPS). In this study we used multivariate-pattern-analysis with human fMRI data to investigate whether the WM representations in the PMC, IPS or other regions are influenced by changing task demands. We ensured the task-dependent, categorical WM information was decorrelated from stimulus features by (1) teaching participants arbitrary, non-rule based stimulus groupings and (2) contrasting identical pairs of stimuli across experimental conditions, where either a single stimulus or the associated group was maintained in WM. Importantly, we also decoupled the decision and motor output from the WM representations. With these experimental manipulations, we were able to pinpoint stimulus-specific WM information to the left frontal and parietal cortices and context-dependent, group-specific WM information to the left IPS. By showing that grouped stimuli are represented more similarly in the Group condition than in the Stimulus condition, free from stimulus and motor output confounds, we provide novel evidence for the adaptive nature of somatosensory WM representations in the IPS with changing task-demands

Multi-sensory working memory - in vision, audition and touch

Our nervous systems can perform a vast variety of cognitive tasks, many involving several different senses. Although sensory systems provide a basis for the creation of mental representations, we rely on memory to form mental representations of information that is no longer present in our external world. Focussing on the initial stage of this process, working memory (WM), where information is retained actively over a short time course, experiments included in this thesis were directed toward understanding the nature of sensory representations across the senses (vision, audition and touch). Instead of quantifying how many items one can hold in each sensory modality (all-or-none representations), new response methods were devised to capture the qualitative nature of sensory representations. Measuring quality rather than quantity of information held in WM, has led to the re-evaluation of the nature of its underlying capacity limits. Rather than assuming that WM capacity is limited to a fixed number of items, it may be more suitable to describe WM as a resource which can be shared and flexibly distributed across sensory information. Thus it has been proposed that at low loads we can hold information at a high resolution. However, as soon as memory load is increased, there is a deterioration of the quality at which each individual item can be represented in WM. The resource model of WM has been applied to describe processes of visual WM, but has not been investigated for other sensory modalities. In the first part of my thesis I demonstrate behaviourally that the resource model can be extended to account for processes in auditory WM, associated with the storage of sound frequency (pitch, chapter 2) and speech sounds (phonemes, chapter 3). I then show that it can also be extended to account for storage of tactile vibrational frequencies (chapter 4). Overall, the results suggest that memory representations become noisier with an increase in information load, consistent with the concept that representations are coded as distributed patterns. A pattern may code for individual object features or entire objects. As studies in chapter 2 - 4 only looked at a single type of feature each in separation, I next examined WM information storage for auditory objects, composed of multiple features (chapter 5). Object formation involves binding of features, which become reorganized to create more complex unified representations of previously distributed information. The results revealed a clear feature extraction cost when recall was tested on individual features rather than on integrated objects. One interpretation of these findings is that, at some level in the auditory system, sounds may be stored as integrated objects. In a final study, using fMRI with MVPA (mulitvoxel pattern analysis), memory traces represented as distributed patterns of brain activity were decoded from different regions of the auditory system (chapter 6). The major goal was to resolve the debate on the role of early sensory cortices in cognition: are they primarily involved in the perception of low-level stimulus features or also in maintenance of the same features in memory? I demonstrate that perception and memory share common neural substrates, where early auditory cortex serves as a substrate to accommodate both processes. Overall, in this thesis memory representations were characterized across the senses in three different ways: (1) measuring them in terms of their quality or resolution, (2) testing whether the preferred format is on the feature or integrated object level; and (3) as patterns of brain activity. Findings converge along the concept that noisy representations actively held in WM are coded as distributed patterns in the brain

EEG and ECoG features for Brain Computer Interface in Stroke Rehabilitation

The ability of non-invasive Brain-Computer Interface (BCI) to control an exoskeleton was used for motor rehabilitation in stroke patients or as an assistive device for the paralyzed. However, there is still a need to create a more reliable BCI that could be used to control several degrees of Freedom (DoFs) that could improve rehabilitation results. Decoding different movements from the same limb, high accuracy and reliability are some of the main difficulties when using conventional EEG-based BCIs and the challenges we tackled in this thesis. In this PhD thesis, we investigated that the classification of several functional hand reaching movements from the same limb using EEG is possible with acceptable accuracy. Moreover, we investigated how the recalibration could affect the classification results. For this reason, we tested the recalibration in each multi-class decoding for within session, recalibrated between-sessions, and between sessions. It was shown the great influence of recalibrating the generated classifier with data from the current session to improve stability and reliability of the decoding. Moreover, we used a multiclass extension of the Filter Bank Common Spatial Patterns (FBCSP) to improve the decoding accuracy based on features and compared it to our previous study using CSP. Sensorimotor-rhythm-based BCI systems have been used within the same frequency ranges as a way to influence brain plasticity or controlling external devices. However, neural oscillations have shown to synchronize activity according to motor and cognitive functions. For this reason, the existence of cross-frequency interactions produces oscillations with different frequencies in neural networks. In this PhD, we investigated for the first time the existence of cross-frequency coupling during rest and movement using ECoG in chronic stroke patients. We found that there is an exaggerated phase-amplitude coupling between the phase of alpha frequency and the amplitude of gamma frequency, which can be used as feature or target for neurofeedback interventions using BCIs. This coupling has been also reported in another neurological disorder affecting motor function (Parkinson and dystonia) but, to date, it has not been investigated in stroke patients. This finding might change the future design of assistive or therapeuthic BCI systems for motor restoration in stroke patients

Die neurophysiologischen Grundlagen von Arbeitsgedächtnisdefiziten bei der Schizophrenie

The pathophysiology of schizophrenia is still poorly understood. Investigating the neurophysiological correlates of cognitive dysfunction with functional neuroimaging techniques such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) is widely considered to be a possible solution for this problem. Working memory impairment is one of the most prominent cognitive impairments found in schizophrenia. Working memory can be divided into a number of component processes, encoding, maintenance and retrieval. They appear to be differentially affected in schizophrenia, but little is known about the neurophysiological disturbances which contribute to deficits in these component processes. The aim of this dissertation was to elucidate the neurophysiological underpinnings of the component processes of working memory and their disturbance in schizophrenia. In the first study the the neurophysiological substrates of visual working memory capacity limitations were investigated during encoding, maintenance and retrieval in 12 healthy subjects using event-related fMRI. Subjects had to encode up to four abstract visual shapes and maintain them in working memory for 12 seconds. Afterwards a test stimulus was presented, which matched one of the previously shown shapes in fifty percent of the trials. A bilateral inverted U-shape pattern of BOLD activity with increasing memory load in areas closely linked with selective attention, i.e. the frontal eye fields and areas around the intraparietal sulcus, was observed already during encoding. The increase of the number of stored items from memory load three to memory load four in these regions was negatively correlated with the increase of BOLD activity from memory load three to memory load four. These results point to a crucial role of attentional processes for the limited capacity of working memory. In the second study, the contribution of early perceptual processing deficits during encoding and retrieval to working memory dysfunction was investigated in 17 patients with schizophrenia and 17 healthy control subjects using EEG and event-related fMRI. A slightly modified version of the working memory task used in the fist study was employed. Participants only had to encode and maintain up to three items. In patients the amplitude of the P1 event-related potential was significantly reduced already during encoding in all memory load conditions. Similarly, BOLD activity in early visual areas known to generate the P1 was significantly reduced in patients. In controls, a stronger P1 amplitude increase with increasing memory load predicted better performance. These findings indicate that in addition to later memory related processing stages early visual processing is disturbed in schizophrenia and contributes to working memory dysfunction by impairing the encoding of information. In the third study, which was based on the same data set as the second study, cortical activity and functional connectivity in 17 patients with schizophrenia and 17 to healthy control subjects during the working memory encoding, maintenance and retrieval was investigated using event-related fMRI. Patients had reduced working memory capacity. During encoding activation in the left ventrolateral prefrontal cortex and extrastriate visual cortex was reduced in patients but positively correlated with working memory capacity in controls. During early maintenance patients switched from hyper- to hypoactivation with increasing memory load in a fronto-parietal network which included left dorsolateral prefrontal cortex. During retrieval right ventrolateral prefrontal hyperactivation was correlated with encoding-related hypoactivation of left ventrolateral prefrontal cortex in patients. Cortical dysfunction in patients during encoding and retrieval was accompanied by abnormal functional connectivity between fronto-parietal and visual areas. These findings indicate a primary encoding deficit in patients caused by a dysfunction of prefrontal and visual areas. The findings of these studies suggest that isolating the component processes of working memory leads to more specific markers of cortical dysfunction in schizophrenia, which had been obscured in previous studies. This approach may help to identify more reliable biomarkers and endophenotypes of schizophrenia.Die Pathophysiologie der Schizophrenie ist noch immer weitgehend unverstanden. Die Untersuchung der neurophysiologischen Grundlagen kognitiver Störungen mit den Methode der funktionellen Bildgebung wie der Elektroenzephalographie (EEG) und der funktionellen Magnetresonanztomographie (fMRT) wird als mögliche Lösung für dieses Problem angesehen. Störungen des Arbeitsgedächtnisses sind eines der bedeutendsten kognitive Defizite der Schizophrenie. Das Arbeitsgedächtnis kann in eine Reihe von Subprozessen eingeteilt werden, die Enkodierung, das Halten und das Abrufen von Information. Diese Subprozesse scheinen bei der Schizophrenie in differenzieller Weise beeinträchtigt zu sein, über die zugrundeliegenden neurophysiologischen Störungen ist jedoch sehr wenig bekannt. Das Ziel dieser Dissertation ist die Untersuchung der neurophysiologischen Grundlagen dieser Arbeitsgedächtnissubprozesse und ihrer Störung bei der Schizophrenie. In der ersten Studie wurden die neurophysiologischen Korrelate der Kapazitätsbegrenzungen des Arbeitsgedächtnisses während der Enkodierung, des Halten und des Abrufen von Information in 12 gesunden Probanden mittels fMRT untersucht. Die Probanden mußten bis zu vier abstrakte Figuren enkodieren und für 12 Sekunden im Arbeitsgedächtnis behalten. Anschließend wurde ein Testreiz präsentiert, der in fünfzig Prozent der Fälle mit einem der vorher gezeigten Figuren übereinstimmte. Während der Enkodierung zeigte sich mit steigender Arbeitsgedächtnisbelastung in den frontalen Augenfeldern und im Bereich des Sulcus intraparietalis, die beide eng mit selektiver Aufmerksamkeit verknüpft sind, beidseits ein Aktivierungsmuster in Form eines invertierten U. Für den Anstieg der Anzahl der erfolgreich gespeicherten Objekte fand sich in den beiden schwierigsten Bedingungen eine negative Korrelation mit dem Aktivierungsanstieg in diesen Regionen. Diese Ergebnisse weisen auf eine wichtige Rolle von Aufmerksamkeitsprozessen für die Begrenzung der Arbeitsgedächtniskapazität hin. In der zweiten Studie wurde die Rolle von Störungen früher perzeptueller Verarbeitungsschritte während der Enkodierung und dem Abrufen von Information aus dem Arbeitsgedächtnis mittels EEG und fMRT bei 17 Patienten mit Schizophrenie und 17 gesunden Kontrollprobanden untersucht. Es wurde eine leicht modifizierte Variante der Aufgabe der ersten Studie verwendet, bei der die Versuchspersonen maximal drei Objekte enkodieren mußten. Bei den Patienten fand sich eine reduzierte Amplitude der P1 während der Enkodierung unabhängig von der Zahl der zu merken Objekte. In frühen visuellen Arealen, die für die Entstehung der P1 verantwortlich sind, zeigte sich ebenso eine verminderte Hirnaktivität. Bei den Kontrollprobanden war eine stärkerer P1 Amplitudenanstieg mit steigender Zahl der Objekte mit einer höheren Antwortrichtigkeit assoziiert. Dies Befunde weisen darauf hin, daß zusätzlich zu späteren Gedächtnisprozessen die führe visuelle Verarbeitung bei der Schizophrenie gestört ist und die Enkodierung von Informationen beeinträchtigt. In der dritten Studie, die auf dem gleichen Datensatz wie die zweite Studie basiert, wurde die kortikale Hirnaktivität sowie die funktionelle Konnektivität während der Enkodierung, dem Halten und dem Abrufen von Information mittels fMRT bei 17 Patienten mit Schizophrenie und 17 gesunden Kontrollprobanden untersucht. Die Arbeitsgedächtniskapazität der Patienten war reduziert. Während der Enkodierung war die Aktivität des linken ventrolateralen präfrontalen Kortex und des extrastriatären visuellen Kortex bei den Patienten reduziert. Bei den Kontrollprobanden fand sich in diesen Arealen eine positive Korrelation zwischen Hirnaktivität und Arbeitsgedächtniskapazität. Während der frühen Haltephase wechselten die Patienten mit steigender Objektzahl von einer präfrontalen Über- zu einer Minderaktivierung eines frontoparietalen Netzwerks, welches den linken dorsolateralen präfrontalen Kortex mit einschloss. Die Überaktivierung des rechten ventrolateralen präfrontalen Kortex während der Abrufphase korrelierte bei den Patienten mit der Minderaktivierung des linken ventrolateralen präfrontalen Kortex während der Enkodierung. Während der Enkodierung und dem Abrufen fand sich eine gestörte funktionellen Konnektivität zwischen frontoparietalen und visuellen Arealen. Diese Befunde weisen auf ein primäres Enkodierungsdefizit als Folge einer Dysfunktion präfrontaler und visueller Areale bei den Patienten hin. Die Ergebnisse der Studien deuten darauf hin, daß die getrennte Untersuchung der Arbeitsgedächtnissubkomponenten zu spezifischeren Markern kortikaler Dysfunktion bei den Patienten führen, die in früheren Studien verdeckt geblieben waren. Dieser Ansatz könnte dabei helfen, reliablere Biomarker und Endophäntoypen für die Schizophrenie zu identifizieren

ELECTROPHYSIOLOGICAL MECHANISMS FOR PREPARING CONTROL IN TIME

Cognitive control is critical in guiding goal-directed behavior, preparing neural resources and adapting processing to promote optimal action in a given environment. According to the Dual Mechanisms of Control theory (Braver, 2012), control can be dichotomized into proactive and reactive modes of control, utilized reciprocally in ahead-of-time preparation versus last-minute, stimulus-evoked reaction. Although a substantial body of work has tested differences between proactive control and reactive control, the underlying assumption of proactive control as a unitary process has not been systematically investigated. Very little is known as to how or when proactive control is initiated, sustained, or implemented. As time is an integral building block of perception, cognition, and action (Buhusi & Meck, 2005), one should expect temporal information to be integrated into proactive control. Cognitive control is costly (Shenhav, Botvinick, & Cohen, 2013), and a temporally-guided modulation of control may offer substantial cost savings. By measuring proactive control on a sub-second time-scale, we can begin to gauge whether dissociable sub-types of proactive control are utilized demanding on temporal demands. Moreover, by comparing proactive control processes across different temporal demands, we can parse out when different aspects of control are computed and implemented. Through a meta-analytic review and three empirical experiments, this dissertation provides insight into how timing dynamics may influence the computation, maintenance, and instantiation of proactive cognitive control. First, a meta-analysis on the cued control literature reveals that seemingly trivial experimental parameters shape the use of proactive versus reactive control. Two EEG studies then demonstrate how modulating timing dynamics influences prefrontal mechanisms for preparatory cognitive control. In a final EEG study, we compare the mechanisms utilized to retain control goals versus visuo-spatial working memory items. Overall, this dissertation elucidates several novel electrophysiological mechanisms by which timing information is implemented in the computation and retention of cognitive control rules. Further, we provide evidence that individual differences in impulsivity and working memory shape distinct aspects of preparation. The findings reported here make clear that timing information is critical in guiding proactive control processes, and support a fundamental reconsideration of proactive control based on temporal dynamics