A Tablet-Based Assessment of Rhythmic Ability.

The exponential rise in use of mobile consumer electronics has presented a great potential for research to be conducted remotely, with participants numbering several orders of magnitude greater than a typical research paradigm. Here, we attempt to demonstrate the validity and reliability of using a consumer game-engine to create software presented on a mobile tablet to assess sensorimotor synchronization, a proxy of rhythmic ability. Our goal was to ascertain whether previously observed research results can be replicated, rather than assess whether a mobile tablet achieves comparable performance to a desktop computer. To achieve this, younger (aged 18-35 years) and older (aged 60-80 years) adult musicians and non-musicians were recruited to play a custom-designed sensorimotor synchronization assessment on a mobile tablet in a controlled laboratory environment. To assess reliability, participants performed the assessment twice, separated by a week, and an intra-class correlation coefficient (ICC) was calculated. Results supported the validity of this approach to assessing rhythmic abilities by replicating previously observed results. Specifically, musicians performed better than non-musicians, and younger adults performed better than older adults. Participants also performed best when the tempo was in the range of previously-identified preferred tempos, when the stimuli included both audio and visual information, and when synchronizing on-beat compared to off-beat or continuation (self-paced) synchronization. Additionally, high ICC values (>0.75) suggested excellent test-retest reliability. Together, these results support the notion that consumer electronics running software built with a game engine may serve as a valuable resource for remote, mobile-based data collection of rhythmic abilities

Experiments in time:exploring the components of motor timing behaviour in dyslexia

This investigation aimed to pinpoint the elements of motor timing control that are responsible for the increased variability commonly found in children with developmental dyslexia on paced or unpaced motor timing tasks (Chapter 3). Such temporal processing abilities are thought to be important for developing the appropriate phonological representations required for the development of literacy skills. Similar temporal processing difficulties arise in other developmental disorders such as Attention Deficit Hyperactivity Disorder (ADHD). Motor timing behaviour in developmental populations was examined in the context of models of typical human timing behaviour, in particular the Wing-Kristofferson model, allowing estimation of the contribution of different timing control systems, namely timekeeper and implementation systems (Chapter 2 and Methods Chapters 4 and 5). Research examining timing in populations with dyslexia and ADHD has been inconsistent in the application of stimulus parameters and so the first investigation compared motor timing behaviour across different stimulus conditions (Chapter 6). The results question the suitability of visual timing tasks which produced greater performance variability than auditory or bimodal tasks. Following an examination of the validity of the Wing-Kristofferson model (Chapter 7) the model was applied to time series data from an auditory timing task completed by children with reading difficulties and matched control groups (Chapter 8). Expected group differences in timing performance were not found, however, associations between performance and measures of literacy and attention were present. Results also indicated that measures of attention and literacy dissociated in their relationships with components of timing, with literacy ability being correlated with timekeeper variance and attentional control with implementation variance. It is proposed that these timing deficits associated with reading difficulties are attributable to central timekeeping processes and so the contribution of error correction to timing performance was also investigated (Chapter 9). Children with lower scores on measures of literacy and attention were found to have a slower or failed correction response to phase errors in timing behaviour. Results from the series of studies suggest that the motor timing difficulty in poor reading children may stem from failures in the judgement of synchrony due to greater tolerance of uncertainty in the temporal processing system

Functional integration in the cortical neuronal network of conscious and anesthetized animals

General anesthesia consists of amnesia, analgesia, areflexia and unconsciousness. How anesthetics suppress consciousness has been a mystery for more than one and a half centuries. The overall goal of my research has been to determine the neural correlates of anesthetic-induced loss of consciousness. I hypothesized that anesthetics induce unconsciousness by interfering with the functional connectivity of neuronal networks of the brain and consequently, reducing the brain\u27s capacity for information processing. To test this hypothesis, I performed experiments in which neuronal spiking activity was measured with chronically implanted microelectrode arrays in the visual cortex of freely-moving rats during wakefulness and at graded levels of anesthesia produced by the inhalational anesthetic agent desflurane. I then applied linear and non-parametric information-theoretic analyses to quantify the concentration-dependent effect of general anesthetics on spontaneous and visually evoked spike firing activity in rat primary visual cortex. Results suggest that desflurane anesthesia disrupts cortical neuronal integration as measured by monosynaptic connectivity, spike burst coherence and information capacity. This research furthers our understanding of the mechanisms involved with the anesthetic-induced LOC which may facilitate in the development of better anesthetic monitoring devices and the creation of effective anesthetic agents that will be free of unwanted side effects

Involvement of fast-spiking cells in ictal sequences during spontaneous seizures in rats with chronic temporal lobe epilepsy

Epileptic seizures represent altered neuronal network dynamics, but the temporal evolution and cellular substrates of the neuronal activity patterns associated with spontaneous seizures are not fully understood. We used simultaneous recordings from multiple neurons in the hippocampus and neocortex of rats with chronic temporal lobe epilepsy to demonstrate that subsets of cells discharge in a highly stereotypical sequential pattern during ictal events, and that these stereotypical patterns were reproducible across consecutive seizures. In contrast to the canonical view that principal cell discharges dominate ictal events, the ictal sequences were predominantly composed of fast-spiking, putative inhibitory neurons, which displayed unusually strong coupling to local field potential even before seizures. The temporal evolution of activity was characterized by unique dynamics where the most correlated neuronal pairs before seizure onset displayed the largest increases in correlation strength during the seizures. These results demonstrate the selective involvement of fast spiking interneurons in structured temporal sequences during spontaneous ictal events in hippocampal and neocortical circuits in experimental models of chronic temporal lobe epilepsy

The influence of external and internal motor processes on human auditory rhythm perception

Musical rhythm is composed of organized temporal patterns, and the processes underlying rhythm perception are found to engage both auditory and motor systems. Despite behavioral and neuroscience evidence converging to this audio-motor interaction, relatively little is known about the effect of specific motor processes on auditory rhythm perception. This doctoral thesis was devoted to investigating the influence of both external and internal motor processes on the way we perceive an auditory rhythm. The first half of the thesis intended to establish whether overt body movement had a facilitatory effect on our ability to perceive the auditory rhythmic structure, and whether this effect was modulated by musical training. To this end, musicians and non-musicians performed a pulse-finding task either using natural body movement or through listening only, and produced their identified pulse by finger tapping. The results showed that overt movement benefited rhythm (pulse) perception especially for non-musicians, confirming the facilitatory role of external motor activities in hearing the rhythm, as well as its interaction with musical training. The second half of the thesis tested the idea that indirect, covert motor input, such as that transformed from the visual stimuli, could influence our perceived structure of an auditory rhythm. Three experiments examined the subjectively perceived tempo of an auditory sequence under different visual motion stimulations, while the auditory and visual streams were presented independently of each other. The results revealed that the perceived auditory tempo was accordingly influenced by the concurrent visual motion conditions, and the effect was related to the increment or decrement of visual motion speed. This supported the hypothesis that the internal motor information extracted from the visuomotor stimulation could be incorporated into the percept of an auditory rhythm. Taken together, the present thesis concludes that, rather than as a mere reaction to the given auditory input, our motor system plays an important role in contributing to the perceptual process of the auditory rhythm. This can occur via both external and internal motor activities, and may not only influence how we hear a rhythm but also under some circumstances improve our ability to hear the rhythm.Musikalische Rhythmen bestehen aus zeitlich strukturierten Mustern akustischer Stimuli. Es konnte gezeigt werden, dass die Prozesse, welche der Rhythmuswahrnehmung zugrunde liegen, sowohl motorische als auch auditive Systeme nutzen. Obwohl sich für diese auditiv-motorischen Interaktionen sowohl in den Verhaltenswissenschaften als auch Neurowissenschaften übereinstimmende Belege finden, weiß man bislang relativ wenig über die Auswirkungen spezifischer motorischer Prozesse auf die auditive Rhythmuswahrnehmung. Diese Doktorarbeit untersucht den Einfluss externaler und internaler motorischer Prozesse auf die Art und Weise, wie auditive Rhythmen wahrgenommen werden. Der erste Teil der Arbeit diente dem Ziel herauszufinden, ob körperliche Bewegungen es dem Gehirn erleichtern können, die Struktur von auditiven Rhythmen zu erkennen, und, wenn ja, ob dieser Effekt durch ein musikalisches Training beeinflusst wird. Um dies herauszufinden wurde Musikern und Nichtmusikern die Aufgabe gegeben, innerhalb von präsentierten auditiven Stimuli den Puls zu finden, wobei ein Teil der Probanden währenddessen Körperbewegungen ausführen sollte und der andere Teil nur zuhören sollte. Anschließend sollten die Probanden den gefundenen Puls durch Finger-Tapping ausführen, wobei die Reizgaben sowie die Reaktionen mittels eines computerisierten Systems kontrolliert wurden. Die Ergebnisse zeigen, dass offen ausgeführte Bewegungen die Wahrnehmung des Pulses vor allem bei Nichtmusikern verbesserten. Diese Ergebnisse bestätigen, dass Bewegungen beim Hören von Rhythmen unterstützend wirken. Außerdem zeigte sich, dass hier eine Wechselwirkung mit dem musikalischen Training besteht. Der zweite Teil der Doktorarbeit überprüfte die Idee, dass indirekte, verdeckte Bewegungsinformationen, wie sie z.B. in visuellen Stimuli enthalten sind, die wahrgenommene Struktur von auditiven Rhythmen beeinflussen können. Drei Experimente untersuchten, inwiefern das subjektiv wahrgenommene Tempo einer akustischen Sequenz durch die Präsentation unterschiedlicher visueller Bewegungsreize beeinflusst wird, wobei die akustischen und optischen Stimuli unabhängig voneinander präsentiert wurden. Die Ergebnisse zeigten, dass das wahrgenommene auditive Tempo durch die visuellen Bewegungsinformationen beeinflusst wird, und dass der Effekt in Verbindung mit der Zunahme oder Abnahme der visuellen Geschwindigkeit steht. Dies unterstützt die Hypothese, dass internale Bewegungsinformationen, welche aus visuomotorischen Reizen extrahiert werden, in die Wahrnehmung eines auditiven Rhythmus integriert werden können. Zusammen genommen, 5 zeigt die vorgestellte Arbeit, dass unser motorisches System eine wichtige Rolle im Wahrnehmungsprozess von auditiven Rhythmen spielt. Dies kann sowohl durch äußere als auch durch internale motorische Aktivitäten geschehen, und beeinflusst nicht nur die Art, wie wir Rhythmen hören, sondern verbessert unter bestimmten Bedingungen auch unsere Fähigkeit Rhythmen zu identifizieren

Novel measure of olfactory bulb function in health and disease

Present neuroimaging techniques are capable of recording the neural activity from all over the brain but the olfactory bulb (OB). The OB is the first olfactory processing stage of the central nervous system and the site of insult in several neurological disorders, particularly Parkinson’s disease (PD). It has been suggested that the OB has a pivotal role in the olfactory system anal-ogous to primary visual cortex (V1) and thalamus in the visual system. However, due to the existing technical limitations, there has not been any non-invasive technique that can reliably measure the OB function in humans, consequently limiting its functional recording to one in-tracranial study dating back to the 60s. Initially in Study I, a non-invasive method of measuring the function of human OB is devel-oped, so-called electrobulbogram (EBG). In line with previous animal literature as well as the only intracranial study in human OB, it was demonstrated that gamma oscillations on the EBG electrodes occurred shortly after the odor onset. Subsequently, applying source recon-struction analysis provided evidence that observed oscillations were localized to the OB. Ad-ditionally, the OB recording with the EBG method showed a test-retest reliability comparable with visual event related potentials. Notably, the detected gamma oscillations were demon-strated to be insensitive to habituation, the OB’s marked characteristic which has previously been demonstrated in rodents. Last, but not least, assessing the EBG response in an individual who did not have the bilateral OB indicated that the lack of OB results in disappearance of gamma oscillations in the EBG electrodes. Given that Study I determined the possibility of reliably measuring the function of the OB using the EBG, in Study II, I assessed the functional role of OB’s oscillations in the pro-cessing of the odor valence. Odor valence has been suggested to be linked to approach–avoidance responses and therefore, processing of odor valence is thought to be one of the core aspects of odor processing in the olfactory system. Consequently, using combined EBG and EEG recording, OB activity was reconstructed on the source level during processing of odors with different valences. Gamma and beta oscillations were found to be related to va-lence perception in the human OB. Moreover, the early beta oscillations were associated with negative but not positive odors, where these beta oscillations can be linked to preparatory neural responses in the motor cortex. Subsequently, in a separate experiment, negative odors were demonstrated to trigger a whole-body motor avoidance response in the time window overlapping with the valence processes in the OB. These negative odor-elicited motor re-sponses were measured by a force plate as a leaning backward motion. Altogether, the results from Study II indicated that the human OB processes odor valence sequentially in the gamma and beta frequency bands, where the early processing of negative odors in the OB might be facilitating rapid approach-avoidance behaviors. To further evaluate the functional role of the OB in odor processing, in Study III, OB’s communication with its immediate recipient, namely piriform cortex (PC), was assessed. These two areas are critical nodes of the olfactory system which communicate with each other through neural oscillations. The activity of the OB and the PC were reconstructed using a combination of EBG, EEG, and source reconstruction techniques. Subsequently, the cross spectrogram of the OB and the PC was assessed as a measure of functional connectivity where temporal evolution from fast to slow oscillations in the OB–PC connectivity was found during the one second odor processing. Furthermore, the spectrally resolved Granger causal-ity analysis suggested that the afferent connection form the OB to the PC occurred in the gamma and beta bands whereas the efferent connection from the PC to the OB was concen-trated in the theta and delta bands. Notably, odor identity could be deciphered from the low gamma oscillatory pattern in the OB–PC connectivity as early as 100ms after the odor onset. Hence, findings from this study elucidate on our understanding of the bidirectional infor-mation flow in the human olfactory system. Olfactory dysfunction, due to neurodegeneration in the OB, commonly appears several years earlier than the occurrence of the PD-related characteristic motor symptoms. Consequently, a functional measure of the OB may serve as a potential early biomarker of PD. In Study IV, OB function was assessed in PD to answer whether the EBG method can be used to dissociate individuals with a PD diagnosis from healthy age-matched controls. The spectrogram of the EBG signals indicated that there were different values in gamma, beta, and theta for PDs compared with healthy controls. Specifically, six components were found in the EBG re-sponse during early and late time points which together dissociate PDs from controls with a 90% sensitivity and a 100% specificity. Furthermore, these components were linked to med-ication, disease duration and severity, as well as clinical odor identification performance. Overall, these findings support the notion that EBG has a diagnostic value and can be further developed to serve as an early biomarker for PD. In the last study, Study V, the prevalence of COVID-19 was determined using odor intensity ratings as an indication of olfactory dysfunction. Using a large sample data (n = 2440) from a Swedish population, odor intensity ratings of common household items over time were found to be closely associated with prevalence prediction of COVID-19 in the Stockholm region over the same time-period (r = -.83). Impairment in odor intensity rating was further correlated with the number of reported COVID-19 symptoms. Relatedly, individuals who progressed from having no symptoms to having at least one symptom had a marked decline in their odor intensity ratings. The results from this study, given the relatively large sample size, provided a concrete basis for the future studies to further assess the potential association between the deficits in the OB function and olfactory dysfunction in COVID-19. In conclusion, our proposed method for non-invasive measurement of the OB function was shown to provide a reliable recording with a potential as a diagnostic tool for PD. Combining EBG and EEG allowed for reconstruction of the OB signal at the source level, where specific oscillations were found to be critical for odor valence processing and rapid avoidance re-sponse. Moreover, oscillations in different frequency bands were found to be critical for the OB reciprocal communications and transfer of odor identity information to higher order ol-factory subsystems. Finally, COVID-19 was found to be associated with a decline in olfactory acuity which might originate from damage to the patient’s OB. In conclusion, the results from the studies within this thesis provide a new perspective on the functional role of oscillations in the human OB

Structure of Spontaneous UP and DOWN Transitions Self-Organizing in a Cortical Network Model

Synaptic plasticity is considered to play a crucial role in the experience-dependent self-organization of local cortical networks. In the absence of sensory stimuli, cerebral cortex exhibits spontaneous membrane potential transitions between an UP and a DOWN state. To reveal how cortical networks develop spontaneous activity, or conversely, how spontaneous activity structures cortical networks, we analyze the self-organization of a recurrent network model of excitatory and inhibitory neurons, which is realistic enough to replicate UP–DOWN states, with spike-timing-dependent plasticity (STDP). The individual neurons in the self-organized network exhibit a variety of temporal patterns in the two-state transitions. In addition, the model develops a feed-forward network-like structure that produces a diverse repertoire of precise sequences of the UP state. Our model shows that the self-organized activity well resembles the spontaneous activity of cortical networks if STDP is accompanied by the pruning of weak synapses. These results suggest that the two-state membrane potential transitions play an active role in structuring local cortical circuits