Post-stimulus beta responses are modulated by task duration

Modulation of beta-band neural oscillations during and following movement is a robust marker of brain function. In particular, the post-movement beta rebound (PMBR), which occurs on movement cessation, has been related to inhibition and connectivity in the healthy brain, and is perturbed in disease. However, to realise the potential of the PMBR as a biomarker, its modulation by task parameters must be characterised and its functional role determined. Here, we used MEG to image brain electrophysiology during and after a grip-force task, with the aim to characterise how task duration, in the form of an isometric contraction, modulates beta responses. Fourteen participants exerted a 30% maximum voluntary grip-force for 2, 5 and 10 s. Our results showed that the amplitude of the PMBR is modulated by task duration, with increasing duration significantly reducing PMBR amplitude and increasing its time-to-peak. No variation in the amplitude of the movement related beta decrease (MRBD) with task duration was observed. To gain insight into what may underlie these trial-averaged results, we used a Hidden Markov Model to identify the individual trial dynamics of a brain network encompassing bilateral sensorimotor areas. The rapidly evolving dynamics of this network demonstrated similar variation with task parameters to the ‘classical’ rebound, and we show that the modulation of the PMBR can be well-described in terms of increased frequency of beta events on a millisecond timescale rather than modulation of beta amplitude during this time period. Our results add to the emerging picture that, in the case of a carefully controlled paradigm, beta modulation can be systematically controlled by task parameters and such control can reveal new information as to the processes that generate the average beta timecourse. These findings will support design of clinically relevant paradigms and analysis pipelines in future use of the PMBR as a marker of neuropathology

Multimodal Investigation of Neuronal Responses

This thesis describes an investigation of neuronal responses with both magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). MEG and fMRI are widely used in neuroscience. However, aspects of the MEG and fMRI signal are still not well understood, particularly post-stimulus responses – responses which occur after a stimulus has ended. Post-stimulus responses have been shown to correlate with various illnesses and as a result, MEG and fMRI have yet to reach their full potential clinically. By developing carefully controlled experiments, MEG is used in this thesis to characterise post-stimulus responses to a grip-force task. The results showed that the beta-band post-stimulus response (post-movement beta rebound, PMBR) is modulated by task duration. Functional network analysis, using amplitude envelope correlation and a hidden Markov model, showed that the PMBR re-establishes networks after breaking down during a task, suggesting the PMBR is related to functional connectivity. The results of this thesis provide new information about the nature of the PMBR, demonstrating that it can be systematically controlled by task parameters and provides insight into its generation. It is hoped this research will contribute to a deeper understanding of the PMBR and provide a step forward for its use clinically. In fMRI, the origin of the post-stimulus response is also poorly understood. To investigate fMRI post-stimulus responses, an MR pulse sequence was developed and optimised to measure blood flow, volume and oxygenation changes simultaneously at 7 T. This was implemented with the grip-force task, allowing direct comparison between MEG and fMRI. This study provides new insights into the fMRI post-stimulus undershoot which warrant further investigation. Understanding the link between fMRI and MEG signals will help further understanding of both modalities and how they relate to neuronal activity. Finally, the applications of fMRI were explored by comparing fMRI responses in patients with focal hand dystonia (FHD) with healthy controls. 7 T fMRI was used to map cortical fingertip representations and measures were developed to compare overlap of digit representations between patients and healthy controls. This project provided an important opportunity to advance the understanding of FHD and was the first study to use fMRI to explore the effects of treatment on patients with FHD

Multimodal Investigation of Neuronal Responses

This thesis describes an investigation of neuronal responses with both magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). MEG and fMRI are widely used in neuroscience. However, aspects of the MEG and fMRI signal are still not well understood, particularly post-stimulus responses – responses which occur after a stimulus has ended. Post-stimulus responses have been shown to correlate with various illnesses and as a result, MEG and fMRI have yet to reach their full potential clinically. By developing carefully controlled experiments, MEG is used in this thesis to characterise post-stimulus responses to a grip-force task. The results showed that the beta-band post-stimulus response (post-movement beta rebound, PMBR) is modulated by task duration. Functional network analysis, using amplitude envelope correlation and a hidden Markov model, showed that the PMBR re-establishes networks after breaking down during a task, suggesting the PMBR is related to functional connectivity. The results of this thesis provide new information about the nature of the PMBR, demonstrating that it can be systematically controlled by task parameters and provides insight into its generation. It is hoped this research will contribute to a deeper understanding of the PMBR and provide a step forward for its use clinically. In fMRI, the origin of the post-stimulus response is also poorly understood. To investigate fMRI post-stimulus responses, an MR pulse sequence was developed and optimised to measure blood flow, volume and oxygenation changes simultaneously at 7 T. This was implemented with the grip-force task, allowing direct comparison between MEG and fMRI. This study provides new insights into the fMRI post-stimulus undershoot which warrant further investigation. Understanding the link between fMRI and MEG signals will help further understanding of both modalities and how they relate to neuronal activity. Finally, the applications of fMRI were explored by comparing fMRI responses in patients with focal hand dystonia (FHD) with healthy controls. 7 T fMRI was used to map cortical fingertip representations and measures were developed to compare overlap of digit representations between patients and healthy controls. This project provided an important opportunity to advance the understanding of FHD and was the first study to use fMRI to explore the effects of treatment on patients with FHD

Focusing Attention on the Health Aspects of Foods Changes Value Signals in vmPFC and Improves Dietary Choice

Attention is thought to play a key role in the computation of stimulus values at the time of choice, which suggests that attention manipulations could be used to improve decision-making in domains where self-control lapses are pervasive. We used an fMRI food choice task with non-dieting human subjects to investigate whether exogenous cues that direct attention to the healthiness of foods could improve dietary choices. Behaviorally, we found that subjects made healthier choices in the presence of health cues. In parallel, stimulus value signals in ventromedial prefrontal cortex were more responsive to the healthiness of foods in the presence of health cues, and this effect was modulated by activity in regions of dorsolateral prefrontal cortex. These findings suggest that the neural mechanisms used in successful self-control can be activated by exogenous attention cues, and provide insights into the processes through which behavioral therapies and public policies could facilitate self-control

Modeling single-trial ERP reveals modulation of bottom-up face visual processing by top-down task constraints (in some subjects)

We studied how task constraints modulate the relationship between single-trial event-related potentials (ERPs) and image noise. Thirteen subjects performed two interleaved tasks: on different blocks, they saw the same stimuli, but they discriminated either between two faces or between two colors. Stimuli were two pictures of red or green faces that contained from 10 to 80% of phase noise, with 10% increments. Behavioral accuracy followed a noise dependent sigmoid in the identity task but was high and independent of noise level in the color task. EEG data recorded concurrently were analyzed using a single-trial ANCOVA: we assessed how changes in task constraints modulated ERP noise sensitivity while regressing out the main ERP differences due to identity, color, and task. Single-trial ERP sensitivity to image phase noise started at about 95–110 ms post-stimulus onset. Group analyses showed a significant reduction in noise sensitivity in the color task compared to the identity task from about 140 ms to 300 ms post-stimulus onset. However, statistical analyses in every subject revealed different results: significant task modulation occurred in 8/13 subjects, one showing an increase and seven showing a decrease in noise sensitivity in the color task. Onsets and durations of effects also differed between group and single-trial analyses: at any time point only a maximum of four subjects (31%) showed results consistent with group analyses. We provide detailed results for all 13 subjects, including a shift function analysis that revealed asymmetric task modulations of single-trial ERP distributions. We conclude that, during face processing, bottom-up sensitivity to phase noise can be modulated by top-down task constraints, in a broad window around the P2, at least in some subjects

Driving human motor cortical oscillations leads to behaviorally relevant changes in local GABAA inhibition: a tACS-TMS study

Beta and gamma oscillations are the dominant oscillatory activity in the human motor cortex (M1). However, their physiological basis and precise functional significance remain poorly understood. Here, we used transcranial magnetic stimulation (TMS) to examine the physiological basis and behavioral relevance of driving beta and gamma oscillatory activity in the human M1 using transcranial alternating current stimulation (tACS). tACS was applied using a sham-controlled crossover design at individualized intensity for 20 min and TMS was performed at rest (before, during, and after tACS) and during movement preparation (before and after tACS). We demonstrated that driving gamma frequency oscillations using tACS led to a significant, duration-dependent decrease in local resting-state GABAA inhibition, as quantified by short interval intracortical inhibition. The magnitude of this effect was positively correlated with the magnitude of GABAA decrease during movement preparation, when gamma activity in motor circuitry is known to increase. In addition, gamma tACS-induced change in GABAA inhibition was closely related to performance in a motor learning task such that subjects who demonstrated a greater increase in GABAA inhibition also showed faster short-term learning. The findings presented here contribute to our understanding of the neurophysiological basis of motor rhythms and suggest that tACS may have similar physiological effects to endogenously driven local oscillatory activity. Moreover, the ability to modulate local interneuronal circuits by tACS in a behaviorally relevant manner provides a basis for tACS as a putative therapeutic intervention.SIGNIFICANCE STATEMENT Gamma oscillations have a vital role in motor control. Using a combined tACS-TMS approach, we demonstrate that driving gamma frequency oscillations modulates GABAA inhibition in the human motor cortex. Moreover, there is a clear relationship between the change in magnitude of GABAA inhibition induced by tACS and the magnitude of GABAA inhibition observed during task-related synchronization of oscillations in inhibitory interneuronal circuits, supporting the hypothesis that tACS engages endogenous oscillatory circuits. We also show that an individual's physiological response to tACS is closely related to their ability to learn a motor task. These findings contribute to our understanding of the neurophysiological basis of motor rhythms and their behavioral relevance and offer the possibility of developing tACS as a therapeutic tool

Feedback information and the reward positivity

The reward positivity is a component of the event-related brain potential (ERP) sensitive to neural mechanisms of reward processing. Multiple studies have demonstrated that reward positivity amplitude indices a reward prediction error signal that is fundamental to theories of reinforcement learning. However, whether this ERP component is also sensitive to richer forms of performance information important for supervised learning is less clear. To investigate this question, we recorded the electroencephalogram from participants engaged in a time estimation task in which the type of error information conveyed by feedback stimuli was systematically varied across conditions. Consistent with our predictions, we found that reward positivity amplitude decreased in relation to increasing information content of the feedback, and that reward positivity amplitude was unrelated to trial-to-trial behavioral adjustments in task performance. By contrast, a series of exploratory analyses revealed frontal-central and posterior ERP components immediately following the reward positivity that related to these processes. Taken in the context of the wider literature, these results suggest that the reward positivity is produced by a neural mechanism that motivates task performance, whereas the later ERP components apply the feedback information according to principles of supervised learning

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

The neural basis of responsibility attribution in decision-making

Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent's emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context

Interactions between visual and semantic processing during object recognition revealed by modulatory effects of age of acquisition

The age of acquisition (AoA) of objects and their names is a powerful determinant of processing speed in adulthood, with early-acquired objects being recognized and named faster than late-acquired objects. Previous research using fMRI (Ellis et al., 2006. Traces of vocabulary acquisition in the brain: evidence from covert object naming. NeuroImage 33, 958–968) found that AoA modulated the strength of BOLD responses in both occipital and left anterior temporal cortex during object naming. We used magnetoencephalography (MEG) to explore in more detail the nature of the influence of AoA on activity in those two regions. Covert object naming recruited a network within the left hemisphere that is familiar from previous research, including visual, left occipito-temporal, anterior temporal and inferior frontal regions. Region of interest (ROI) analyses found that occipital cortex generated a rapid evoked response (~ 75–200 ms at 0–40 Hz) that peaked at 95 ms but was not modulated by AoA. That response was followed by a complex of later occipital responses that extended from ~ 300 to 850 ms and were stronger to early- than late-acquired items from ~ 325 to 675 ms at 10–20 Hz in the induced rather than the evoked component. Left anterior temporal cortex showed an evoked response that occurred significantly later than the first occipital response (~ 100–400 ms at 0–10 Hz with a peak at 191 ms) and was stronger to early- than late-acquired items from ~ 100 to 300 ms at 2–12 Hz. A later anterior temporal response from ~ 550 to 1050 ms at 5–20 Hz was not modulated by AoA. The results indicate that the initial analysis of object forms in visual cortex is not influenced by AoA. A fastforward sweep of activation from occipital and left anterior temporal cortex then results in stronger activation of semantic representations for early- than late-acquired objects. Top-down re-activation of occipital cortex by semantic representations is then greater for early than late acquired objects resulting in delayed modulation of the visual response