Optimising the training-induced changes of inhibitory control

In four studies, this thesis examined the effect of task difficulty and brief training on inhibitory processing in the Go/Nogo task, and transfer to the Stop-signal and Eriksenflanker tasks. It also aimed to clarify how the event-related potential (ERP) of the N2 and P3, as well as the earlier N1 and P2 components, reflect training-related modulations in the underlying neural processes. This was achieved by (1) the use of three task difficulty levels (Low, Medium, High) using incremental reaction time deadlines (RTDs), (2) the effect of these three RTDs on task performance and the early (N1, P2) and inhibition-related (N2, P3) ERP components after brief training, (3) the use of another form of task difficulty – stimulus prepotency – to investigate whether training effects may be enhanced, and (4) the use of single Go/Nogo training (planned inhibition) vs. combined training of Go/Nogo (planned inhibition) and Stop-signal (action cancellation) inhibition. The main results were that the Nogo N2 effect was robustly observed to increase with greater task difficulty (i.e. RTDs), but that it reduced irrespective with time-on-task or training condition. It does not appear to reflect neural processing related to motor or pre-motor inhibition, but may instead represent the detection of conflict between responses. The Nogo P3, however, behaved in a fashion consistent with an inhibitory interpretation, being reduced with greater task difficulty (concurrent with lower levels of task performance), but showing increased amplitudes over frontal brain regions with training and improved task performance – an effect that showed near-transfer to an untrained Stop-signal task. Reduced N1, but enhanced P2 amplitudes, occurred regardless of training condition, indicating a generalised change in sensory processing with repeated task administration. The results cast doubt on the current inhibitory interpretation of the N2. Instead they suggest that, not only does the amplitude of the frontocentral Nogo P3 represent neural processing related to inhibitory control, but that it shows clear training-induced quantitative changes coinciding with performance improvements - furthering both the theoretical and applied knowledge of the key task parameters required to effectively train inhibitory control

Neural Correlates of Human Cognition in Real-World Environments

According to embodied accounts of human cognition, the mind is at the interface of the body and the environment. For practical reasons, however, neuroscientific research on human cognition has mostly been confined to the laboratory until now. The emergence of portable brain and body imaging research methods offers an unprecedented opportunity to capture the expression of cognitive processes during active behaviours performed in real-world contexts. In the present thesis, electroencephalography (EEG) was used to investigate embodied aspects of human cognition in motion and in the real-world. This approach, however, presents new challenges in terms of signal processing because of the increased noise related to whole body movements. As the necessary signal processing tools were not well-established, the current work involved the development of new solutions to address the specific requirements of mobile EEG data before real-world brain recordings could be validly interpreted. In a series of Event Related Potential (ERP) experiments, real-world conditions were compared to traditional lab-based conditions. The neural marker of attention (P300 ERP) was recorded when participants performed an attentional task while walking through the university’s corridors versus standing in the lab. Differences in the classic P300 ERP effect show that attentional processes in the real-world are not the same as those recorded in the lab. Following up on this finding, the attenuation of the P300 effect under real-world conditions was shown to be driven by cognitive demands related to displacement through space rather than the act of walking itself. This is a demonstration, at a brain level, that when walking in the real-world, cognitive resources are reallocated to the processing of visual flow and vestibular information associated with displacement. The findings reflect the dynamic interplay between mind, body, and environment, providing innovative evidence strengthening the embodied framework of human cognition. The same dynamic interplay between body, environment and cognitive function is uniquely represented in real-world navigation. The literature on spatial navigation in humans, however, mainly involved navigating virtual reality environments often while lying on a scanner bed. Most of the evidence on the neural markers of spatial navigation comes from intracranially recorded brain oscillations in rodents. The innovation in this thesis was to investigate brain oscillations associated with cognitive function underlying real-world navigation in humans using surface electrodes. The present work demonstrates that human brain dynamics related to navigational cognitive processes can be recorded in active exploration of real-world environments. The key finding resulting from this novel approach is that real-world spatial navigation is associated with specific neural signatures underlying distinct cognitive functions. Frontal low-frequency oscillations were found to be associated with wayfinding, while parietal high-frequency oscillations were associated with spatial memory. Furthermore, these neural correlates were found to be dynamically modulated depending on the body’s contextual positioning within the environment. Therefore, these findings again provide evidence in support of the embodiment theory of cognition. The final study addressed the concern that findings might reflect walking speed variation. The existing animal literature has shown that low-frequency bands are modulated by walking speed. This study characterised the specific modulations in spectral power as a function of walking speed in humans. Critically the pattern showed no similarity to the spectral patterns found in relation to real-world spatial navigation, confirming the cognitive interpretation of this work. Taken together, these findings provide innovative real-world evidence supporting the theoretical embodiment framework. The neural correlates of attention, memory, and spatial navigation were found to be modulated by the dynamic experience of one’s environment. Beyond this work’s theoretical implications for cognitive sciences, the present findings offer new perspectives for real-world application

Electrostimulation Contingencies and Attention, Electrocortical Activity and Neurofeedback

There is a growing body of evidence for diverse ways of modulating neuronal processing to improve cognitive performance. These include brain-based feedback, self-regulation techniques such as EEG-neurofeedback, and stimulation strategies, alone or in combination. The thesis goal was to determine whether a combined strategy would have advantages for normal cognitive function; specifically operant control of EEG activity in combination with transcutaneous electro-acustimulation. In experiment one the association between transcutaneous electroacustimulation (EA) and improved perceptual sensitivity was demonstrated with a visual GO/NOGO attention task (Chen et al, 2011). Furthermore reduced commission errors were related to an electrocortical motor inhibition component during and after alternating high and low frequency EA, whereas habituation in the control group with sham stimulation was related to different independent components. Experiment two applied frequency-domain ICA to detect changes in EEG power spectra from the eyes-closed to the eyes-open state (Chen et al, 2012). A multiple step approach was provided for analysing the spatiotemporal dynamics of default mode and resting state networks of cerebral EEG sources, preferable to conventional scalp EEG data analysis. Five regions were defined, compatible with fMRI studies. In experiment three the EA approach of Exp I was combined with sensorimotor rhythm (SMR) neurofeedback. SMR training improved perceptual sensitivity, an effect not found in a noncontingent feedback group. However, non-significant benefits resulted from EA. With ICA spectral power analysis changes in frontal beta power were associated with contingent SMR training. Possible long-term effects on an attention network in the resting EEG were also found after SMR training, compared with mock SMR training. In conclusion, this thesis has supplied novel evidence for significant cognitive and electrocortical effects of neurofeedback training and transcutaneous electro-acustimulation in healthy humans. Possible implications of these findings and suggestions for future research are considered

Psr1p interacts with SUN/sad1p and EB1/mal3p to establish the bipolar spindle

Regular Abstracts - Sunday Poster Presentations: no. 382During mitosis, interpolar microtubules from two spindle pole bodies (SPBs) interdigitate to create an antiparallel microtubule array for accommodating numerous regulatory proteins. Among these proteins, the kinesin-5 cut7p/Eg5 is the key player responsible for sliding apart antiparallel microtubules and thus helps in establishing the bipolar spindle. At the onset of mitosis, two SPBs are adjacent to one another with most microtubules running nearly parallel toward the nuclear envelope, creating an unfavorable microtubule configuration for the kinesin-5 kinesins. Therefore, how the cell organizes the antiparallel microtubule array in the first place at mitotic onset remains enigmatic. Here, we show that a novel protein psrp1p localizes to the SPB and plays a key role in organizing the antiparallel microtubule array. The absence of psr1+ leads to a transient monopolar spindle and massive chromosome loss. Further functional characterization demonstrates that psr1p is recruited to the SPB through interaction with the conserved SUN protein sad1p and that psr1p physically interacts with the conserved microtubule plus tip protein mal3p/EB1. These results suggest a model that psr1p serves as a linking protein between sad1p/SUN and mal3p/EB1 to allow microtubule plus ends to be coupled to the SPBs for organization of an antiparallel microtubule array. Thus, we conclude that psr1p is involved in organizing the antiparallel microtubule array in the first place at mitosis onset by interaction with SUN/sad1p and EB1/mal3p, thereby establishing the bipolar spindle.postprin

Removal of antagonistic spindle forces can rescue metaphase spindle length and reduce chromosome segregation defects

Regular Abstracts - Tuesday Poster Presentations: no. 1925Metaphase describes a phase of mitosis where chromosomes are attached and oriented on the bipolar spindle for subsequent segregation at anaphase. In diverse cell types, the metaphase spindle is maintained at a relatively constant length. Metaphase spindle length is proposed to be regulated by a balance of pushing and pulling forces generated by distinct sets of spindle microtubules and their interactions with motors and microtubule-associated proteins (MAPs). Spindle length appears important for chromosome segregation fidelity, as cells with shorter or longer than normal metaphase spindles, generated through deletion or inhibition of individual mitotic motors or MAPs, showed chromosome segregation defects. To test the force balance model of spindle length control and its effect on chromosome segregation, we applied fast microfluidic temperature-control with live-cell imaging to monitor the effect of switching off different combinations of antagonistic forces in the fission yeast metaphase spindle. We show that spindle midzone proteins kinesin-5 cut7p and microtubule bundler ase1p contribute to outward pushing forces, and spindle kinetochore proteins kinesin-8 klp5/6p and dam1p contribute to inward pulling forces. Removing these proteins individually led to aberrant metaphase spindle length and chromosome segregation defects. Removing these proteins in antagonistic combination rescued the defective spindle length and, in some combinations, also partially rescued chromosome segregation defects. Our results stress the importance of proper chromosome-to-microtubule attachment over spindle length regulation for proper chromosome segregation.postprin