Hallucination Proneness and Musical Aptitude: Functional and Microstructural Underpinnings

The current thesis aimed to explore links between hallucination proneness and musical aptitude utilising a variety of brain imaging methodologies to characterise associated functional and microstructural individual variabilities. A further aim was to investigate whether a short duration of musical training could be used to modulate functional activity and microstructure in regions associated with hallucinatory experiences. It was hypothesised that hallucination proneness and musical aptitude would be negatively associated with each other and inversely related to underlying functional activity and microstructure within a shared network of brain regions. Moreover, it was hypothesised that musical training would lead to changes in functional activity and microstructure within this shared network of regions. Measures of musical aptitude and hallucination proneness were assessed in conjunction with diffusion imaging models which enabled the characterisation of the microstructural features of the corpus callosum. Results revealed an inverse relationship between musical aptitude and hallucination proneness, with a mediating effect of musical aptitude on hallucination proneness through the microstructure of the corpus callosum. The use of a multi-shell biophysical model, based on neurite orientation dispersion density imaging, further revealed that the relationship between hallucination proneness and musical aptitude was primarily due to callosal neurite orientation dispersion rather than neurite density. With the addition of functional connectivity MRI the degree of callosal neurite orientation dispersion also shown to impact on the functional connectivity during a musical categorisation task, such that higher neurite alignment was associated with increased ROI- ROI fronto-temporal functional connectivity. Hallucination proneness was shown to be negatively associated with performance on a speech perception task and functional connectivity between the left IFG and the superior temporal gyrus (STG) (bilaterally) during task completion. Dendritic complexity within the STG grey matter was also found to be negatively associated with individual variability in propensity to hallucinate. Investigations of the effects of exposure to a short musical training session (learning to tap polyrhythms for one hour) provided evidence of an increase in ROI-ROI function within a bilateral network of fronto-temporal regions following training. Moreover, using three distinct but complimentary diffusion imaging models, polyrhythm training was shown to facilitate a decrease in extra-axonal space diffusion in the central portions of the CC which correlated with performance gains on the polyrhythm discrimination task. The overall results of this thesis therefore support the hypothesis that musical aptitude and hallucination proneness are linked and associated with the underlying microstructure of the CC. Moreover, musical aptitude was shown to be positively associated with task based functional fronto-temporal connectivity whereas hallucination proneness was shown to be negatively associated. Hallucination proneness was further shown to be related to microstructure of the STG with orientation dispersion deemed the most sensitive metric for assessing this relationship. Importantly, results offer evidence that musical training may offer a novel approach for improving fronto-temporal functional connectivity and the microstructure of the corpus callosum, providing an initial foundation for investigation of future novel interventions for hallucinatory experiences

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