Corpus callosum microstructure and auditory interhemispheric transfer in spina bifida myelomeningocele

The purpose of this study was to evaluate if early disruption in corpus callosum development due to spina bifida myelomeningocele (SBM) contributes to plastic reorganization of interhemispheric white matter. Additionally, this study evaluated if diffusion tensor imaging measures of integrity of the interhemispheric temporal tract specifically had functional relevance and predicted performance on a task that required auditory communication between hemispheres, dichotic listening. T1-weighted and diffusion tensor imaging data was acquired on a group of people with SBM (n = 76) and a typically developing group (n = 27). Probabilistic tractography was performed to isolate the interhemispheric white matter connecting auditory processing regions in both hemispheres. Behavioral performance was assessed on a consonant-vowel dichotic listening task in a subset of these participants (SBM, n = 45; TD, n = 15). The key finding from this study was that atypical development of the corpus callosum in SBM does result in re-routing of interhemispheric temporal connections through alternate commissures, particularly the anterior commissure. These re-routed fibers were present in people with SBM and a hypoplastic, or thin posterior corpus callosum, as well as those with more severe underdevelopment, partial agenesis. Additionally, microstructural integrity was reduced in the interhemispheric temporal tract in SBM, as indicated by lower fractional anisotropy and axial diffusivity, and higher radial diffusivity. Examination of macrostructure and microstructure of the tract and dichotic performance suggests that these re-routed connections through the anterior commissure are not compensatory, but maladaptive. Preservation of the normative pattern on the dichotic listening task in people with SBM is the result of connections between temporal lobes through the posterior corpus callosum, and not the anterior commissure. Lastly, abnormal AD was associated with atypical left ear performance on the dichotic listening task, suggesting that reduced integrity of the auditory interhemispheric tract adversely affected dichotic performance in SBM. Given persistent hypotheses about the role of the anterior commissure and other potential compensatory connections, this study has important implications for understanding of the effects of early corpus callosum maldevelopment, especially when partial agenesis is involved.Psychology, Department o

Auditory processing in patients with structural lesions of the brain.

This thesis investigated structure versus function in the central auditory nervous system (CANS) by using the lesion study approach and by utilising a validated clinical test battery for the assessment of auditory processing as well as self- or parent report measures. The central auditory test results were correlated with the macroscopical appearance of the CANS on brain MRI and with patient reported hearing difficulties. The two regions of interest for this study were the insula (first group of studies) and the interhemispheric pathway, comprised by the corpus callosum and the anterior commissure (second group of studies). First group of studies: Patients with a history of ischemic or haemorrhagic cerebral stroke of the CANS were identified by their scans. Exclusion criteria were significant psychiatric or expressive language disorders. Second group of studies: Adults and children with congenital aniridia and abnormality of the interhemispheric pathway due to a PAX6 mutation were recruited. The assessment included questionnaire of auditory capabilities, baseline audiometry (pure tone audiometry, tympanometry and otoacoustic emissions) and central auditory tests (speech and non-speech). The brain MRIs of these patients were visually inspected (1st and 2nd group of studies). The corpus callosum area was measured in the children participants of the 2nd group of studies

The evaluation of interhemispheric transfer time (IHTT) in adults

The goal of the present study was to develop an objective technique to measure interhemispheric transfer time (IHTT) of linguistic stimuli using late auditory evoked potentials to develop normative data in adults. Nine participants, five females and four males (M = 25.22) were included in this study. Each participant had their hearing tested and electrodes were placed on the forehead, tip of the nose, below the right eye and several places on the scalp. The results revealed that when comparing electrode sites (CZ, C3, and C4), waves (P1-N1-P2) and ears (right ear and left ear) there was no statistically significant effect for electrode sites and ears; however, there were for waves. There also were no significant interactions when comparing electrodes to waves, waves to ears, or electrodes to waves to ears. There was also comparison to determine which waves were significantly different from the others. Analysis did not indicate any statistically significant differences between waves P1-N1-P2 when compared for the right versus the left sides. Overall results revealed consistently shorter latencies when the left ear was stimulated compared to when the right ear was stimulated. These results were unexpected and further research is needed with a larger sample size to fully understand how the human auditory system works

Growing up with one ear : central auditory structure and function in unilateral ear canal atresia

The following thesis aims to give more insight into the functional and structural response of the central auditory system to congenital unilateral ear canal atresia (UCA) and the accompanying asymmetric hearing with conductive hearing loss on the atretic side. There is clear evidence that unilateral hearing loss, including UCA, has a negative impact on sound localization ability and perception of speech in noise. There is a spread in performance within the group, and the reason for this is not well known. In paper I of this thesis we examined sound localization with eye tracking and perception of speech in a cocktail party setting, in participants with congenital unilateral ear canal atresia, who had no hearing aids before age 12 (n=12) and compared to normal hearing references. Results show that the level of hearing loss on the atretic ear was associated with sound localization ability but not to speech perception. In the second study, participants with UCA (n=17) underwent MRI-scanning of the brain with diffusion weighted imaging (DWI). A method is described how to segment the white matter bundle between the medial geniculate body of the thalamus and the primary auditory cortex, the acoustic radiation (AR). Methods to define the AR are previously described in high resolution diffusion weighted imaging (DWI) scans but is very time consuming or has problems with including more structures around the primary auditory cortex (PAC). An algorithm was trained to quickly segment the core of the AR in individual clinical scans. The white matter tract was also assessed with measurements of fractional anisotropy (FA), but no differences were found between UCA and normal hearing (NH) controls. The third study describes the measurements of the grey matter of the primary auditory cortex of the Heschl’s gyrus in the same participants as in paper II. Thickness and volume of the Heschl’s gyrus were compared within the groups of UCA and controls, and between the groups. A difference in thickness was found between the left and right side (right thicker than left, corrected p=0.0012) in UCA, whereas controls had symmetric thickness. Volumes and total thickness were not different compared to controls. Rat brains from 12 months old rats with a surgically constructed left-sided ear canal atresia were examined in study IV. DWI was acquired in a research camera for rodents, 9.4 T magnetic field and a prolonged scanning time. Tractography and FA measurements were obtained both from whole brains and from tracts between auditory regions of interest (ROIs) using two different software. FA was generally higher in UCA rats than in controls. The AR was asymmetric in FA (left<right) in UCA, whereas FA was symmetric in controls. The FA was found to be lower at the left connection (same side as hearing loss) cochlear nucleus -inferior colliculus compared to the right side in UCA, while it was symmetric in controls. This finding (CN-IC) aligns with previous histology findings in ferrets with unilateral conductive hearing loss

Influence of beta and theta binaural beat stimulation on episodic memory: an EEG study

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Sinais e Imagens Médicas) Universidade de Lisboa, Faculdade de Ciências, 2021Binaural beats (BBs) are auditory illusions created by the brain when two coherent sounds with slightly different frequencies are presented to both ears dichotically. For example, if the subject is presented a 256 Hz tone to the right ear and a 250 Hz to the left ear, the beat in this phenomenon is referred to as a 6 Hz theta binaural beat. Conversely, a mix of two sinusoids presented to the same ear is called acoustic beat (AB), resulting in a periodic amplitude fluctuation. Although BBs were shown to have positive effects on cognition, there are no sufficient studies on BBs and episodic memory. Furthermore, there is no agreement to explain the brain mechanism underlying the perception of BBs. The primary goal of this study is to investigate the influence of BBs on episodic memory and the effects of BB stimulation on brain rhythms, more concretely to examine whether they can change the power of specific EEG frequencies, comparatively to ABs. The secondary objective focuses on an exploratory study to measure cortical auditory evoked potentials (CAEPs) applying Muse, a consumer-grade EEG device used in this study, in order to assess its potential and the corresponding data quality. To meet the goals, two separate experiments were designed: a classic CAEP paradigm, with a total of 5 participants (3 male, 2 female; aged 22-25 years old); and an experiment with 32 subjects (19 male, 13 female; aged 20-28 years old), divided into two groups (depending on type of stimulation performed: 20 Hz beta or 6 Hz theta beats), each one with two stimuli conditions (BB or AB), received 15 minutes before the episodic memory task, during memory encoding phase and during the free recall test, across 2 sessions with an interval of 1 week. To quantify the power of brain oscillations during AB and BB stimulation, time-frequency analysis was performed using Discrete Wavelet Transform (DWT) and Relative Wavelet Energy (RWE). Regarding CAEP paradigm, N1-P2 complex was detected in temporal regions with acceptable signal-to-noise ratio. Parametric and non-parametric paired t-tests showed several significant changes in RWE values within each group at different time points, frequency bands and channels during both sessions, between BB and AB conditions. Moreover, entrainment of brain activity with the frequency of the beat was detected within theta BB stimulation. Regarding the effects of BB stimulation on episodic memory performance, t-tests revealed significant differences in the memory scores between AB and BB conditions during the first session (t=−2.48, p=0.0133) and second session (t=−2.67, p=0.00914) in theta group, with higher scores observed after BB stimulation. In beta group, significant differences in the scores were observed between AB and BB conditions during first session (t=−2.40, p=0.0154), with higher scores registered in BB condition. Inter-group analysis demonstrated that beta group outperformed theta group in both AB (t=3.37, p=0.00244) and BB (t=3.58, p=0.00143) conditions during the second session. This study validates the use of Muse for neuroscientific research, demonstrating that is possible to rely on consumer-grade low-cost EEG systems. Furthermore, it demonstrates that 20 Hz beta and 6 Hz theta BBs have a positive influence on episodic memory performance. Based on findings of positive effects of BBs on cognition, these results were expected. Entrainment was observed during theta BB stimulation. In addition, it is suggested that BBs have a modulatory effect on brain frequencies, with involvement of dynamical processes.Batimentos binaurais (BBs, do inglês Binaural beats) são ilusões auditivas criadas pelo cérebro quando dois sons coerentes com frequências ligeiramente diferentes são apresentados dicoticamente, isto é, cada ouvido é estimulado por frequências diferentes. Existem diferentes tipos de BBs, dependendo das frequências a partir das quais são criados e da diferença entre elas, o que determina a frequência do batimento. Por exemplo, se o sujeito é apresentado com um tom de 256 Hz no ouvido direito e 250 Hz no ouvido esquerdo, cria-se um batimento binaural de 6 Hz, na frequência do ritmo teta. Por outro lado, a mistura de duas sinusoides apresentadas ao mesmo ouvido possui o nome de batimento acústico (AB, do inglês acoustic beat) e as suas interferências são refletidas em flutuações periódicas em amplitude. Estudos demonstram que os BBs têm um efeito positivo na memória de trabalho, memória de longo prazo, capacidade de atenção e nos níveis de ansiedade e relaxamento. No entanto, existem relatos do seu efeito negativo na atenção e na memória de curto prazo. Para além disso, não existe um consenso na comunidade científica para explicar o mecanismo cerebral subjacente à perceção dos BBs. Tudo isto sublinha a necessidade de mais unificação na pesquisa. Apesar do efeito benéfico dos BBs nos diferentes tipos de memória, não existe um leque de estudos suficientemente grande relativamente à sua influência na memória episódica, um tipo de memória associado à codificação de eventos autobiográficos. Destaques na pesquisa sugerem que as oscilações teta estão associadas a um melhor desempenho na memória episódica. Presumindo que a estimulação auditiva com BBs teta possa ter um efeito modulador das frequências cerebrais por meio de resposta pós-frequência, mais especificamente no ritmo teta, é razoável supor que os BBs podem influenciar a memória episódica. O sistema de EEG usado neste estudo é o Muse, desenvolvido para ajudar em técnicas de meditação. Como não se trata de um aparelho de grau médico, é necessário entender se o material é viável para o estudo. O método para alcançar esta validação foi medir os potenciais evocados auditivos corticais, uma resposta cerebral já bem conhecida. Posto isto, a primeira parte desta tese foca-se num estudo exploratório para medir os potenciais evocados auditivos corticais usando o Muse, com o objetivo de avaliar o potencial do dispositivo e a qualidade dos dados correspondentes. A segunda parte e a meta principal deste estudo é investigar a influência do BBs na memória episódica e estudar o seu efeito nas oscilações cerebrais, em comparação com ABs. Para concretizar a primeira experiência deste estudo, um paradigma clássico foi desenhado para medir os potenciais evocados. Um total de 5 voluntários participaram neste estudo, com idades compreendidas entre 22 e 25 anos. Os participantes receberam um total de 180 estímulos, que consistiam em tons puros de 1000 Hz, com 500 ms de plateau, 10 ms de subida e descida e apresentados a cada 2 segundos. A aquisição do EEG e os marcadores de evento foram concretizados através do Lab Streaming Layer, uma ferramenta que permite criar redes de conexões entre vários dispositivos e programas. O pré-processamento e o processamento dos dados foram executados no EEGLAB, uma extensão do MATLAB que oferece uma interface gráfica para realizar a análise do EEG. Os resultados obtidos foram satisfatórios: o complexo N1-P2 foi identificado em todos os sujeitos e também nas curvas de grande média, com uma melhor relação entre o sinal e o ruído comparativamente às curvas individuais. Relativamente à segunda parte desta tese, a experiência consiste em 2 grupos de sujeitos, 2 blocos de tarefas, cada um com 2 condições de estímulo (AB ou BB), concretizada durante 2 sessões, separadas por uma semana. Um total de 32 voluntários foram recrutados, com idades compreendidas entre 20 e 28 anos. Os sujeitos foram divididos em 2 grupos: grupo teta, que recebeu estimulação com BBs e ABs teta na frequência dos 6 Hz, criados a partir de tons puros de 247 Hz e 253 Hz; grupo beta, que foi estimulado com BBs e ABs beta na frequência dos 20 Hz, gerados a partir de tons puros de 240 Hz e 260 Hz. A primeira parte do primeiro bloco consistia numa tarefa passiva em que os sujeitos de cada grupo ouviam ABs durante 15 minutos, ao mesmo tempo em que aquisição do EEG era realizada. Seguiu-se uma tarefa de memória episódica, em que os participantes tinham que decorar uma sequência de 30 imagens de objetos, cada uma com a duração de 3 segundos. De seguida, uma tarefa de distração foi realizada consistindo numa contagem em voz alta de 20 até 0. Por fim, foi feito um teste de recordação livre em que os sujeitos apontavam num papel os objetos que se lembravam de ver, cujo número seria contabilizado como pontuações de memória. O segundo bloco de tarefas é idêntico ao primeiro, exceto que imagens de objetos diferentes foram usadas e a estimulação durante os 15 minutos iniciais foi feita com BBs. Na segunda sessão, os mesmos procedimentos foram repetidos, exceto o uso de imagens de objetos diferentes em cada bloco. Para quantificar a energia de cada banda de frequência do EEG, recorreu-se à Transformada de Wavelet Discreta, que decompõe o sinal em vários níveis, cada um correspondendo a uma banda de frequência de ritmos cerebrais, e à Energia de Wavelet Relativa (RWE, de Relative Wavelet Energy). Mudanças na RWE dum determinado nível de decomposição refletem mudanças na atividade cerebral na banda de frequências correspondente. Dois tipos de análise foram concretizados: um tendo conta a evolução temporal da RWE ao longo de 13 segmentos de 1 minuto; o segundo implicou calcular a RWE média ao longo de um único segmento de EEG, colapsando a dimensão temporal. Os testes t paramétricos e não paramétricos revelaram várias diferenças entre os valores de RWE durante a estimulação com ABs e a estimulação com BBs, ao longo de diferentes instantes de tempo, bandas de frequências, canais e sessões da experiência. Relativamente ao grupo teta, os testes revelaram que a RWE na banda de frequência alfa no canal AF8 durante a primeira sessão aumentou de AB para BB (t=2.2701, p=0.01919). Durante a segunda sessão, foi observado um aumento dos valores de RWE na banda de frequências teta no canal TP10 da condição AB para BB (t=2.4509, p=0.0135). Relativamente ao grupo beta, as seguintes observações correspondem à primeira sessão, da condição AB para BB: uma diminuição significativa de RWE na banda de frequências beta no canal TP10 (t=-2.3364, p=0.0181) e um aumento significativo de RWE na banda delta no canal TP10 (t=4.3193, p=0.0004164) e no canal TP9 (t=2.7144, p=0.00885). Quanto aos efeitos dos BBs na performance de memória episódica, os testes t revelaram diferenças significativas nas pontuações entre as condições AB e BB durante a primeira sessão (t=-2.48, p=0.0133) e segunda sessão (t=-2.67, p=0.00914) no grupo teta, com pontuações mais altas observadas após a estimulação com BB. No grupo beta, diferenças significativas nas pontuações foram observadas entre as condições AB e BB durante a primeira sessão (t=-2.40, p=0.0154), com pontuações mais elevadas registadoa na condição BB. A análise entre os grupos demonstrou que o grupo beta superou o grupo teta em ambas as condições AB (t=3.37, p=0.00244) e BB (t=3.58, p=0.00143) durante a segunda sessão. Uma análise fatorial ANOVA II demonstrou que o efeito principal da condição foi significativo, sendo que os participantes que foram submetidos à estimulação com batimentos binaurais tiveram resultados mais altos (F(1,115)=5.49, p=0.0208). O efeito principal da sessão também foi significativo, com pontuações mais altas obtidas durante a segunda sessão (F(1,115)=9.206, p=0.00298). Houve interação significativa entre grupo e sessão (F(1,115)=5.11, p=0.0256). Para além disso, regressões lineares demonstraram que o aumento das pontuações de memória está associado ao aumento de RWE na banda de frequências beta (F(5,114) = 5.876, p < 0.0001). Este estudo mostra que é possível quantificar os potenciais evocados auditivos corticais usando um dispositivo de EEG de grau de consumidor. Foi demonstrado que os batimentos binaurais teta de 6 Hz e beta de 20 Hz têm efeito positivo no desempenho da memória episódica, comparativamente aos respetivos acoustic beats. Os participantes que foram estimulados com BBs beta tiveram melhores resultados nos testes de memória comparativamente aos que receberam estimulação com BBs teta, o que pode ser explicado pelo facto da atividade teta, característica da memória episódica, ter sido despertada durante a estimulação BB beta. No entanto, foi demonstrado que o aumento nas pontuações de memória episódica é explicado pelo aumento da RWE no ritmo beta. A resposta pós-frequência foi observada durante a exposição aos BBs teta, porém o mesmo não se verifica relativamente aos BBs beta. Para concluir, este estudo prova que os batimentos binaurais são moduladores neuronais, com envolvimento de respostas dinâmicas. Este efeito modulador da atividade cerebral pode ser a razão por trás da influência destes batimentos na memória episódica

Cortical imbalance following delayed restoration of bilateral hearing in deaf adolescents

Unilateral auditory deprivation in early childhood can lead to cortical strengthening of inputs from the stimulated side, yet the impact of this on bilateral processing when inputs are later restored beyond an early sensitive period is unknown. To address this, we conducted a longitudinal study with 13 bilaterally profoundly deaf adolescents who received unilateral access to sound via a cochlear implant (CI) in their right ear in early childhood before receiving bilateral access to sound a decade later via a second CI in their left ear. Auditory-evoked cortical responses to unilateral and bilateral stimulation were measured repeatedly using electroencephalogram from 1 week to 14 months after activation of their second CI. Early cortical responses from the newly implanted ear and bilateral stimulation were atypically lateralized to the left ipsilateral auditory cortex. Duration of unilateral deafness predicted an unexpectedly stronger representation of inputs from the newly implanted, compared to the first implanted ear, in left auditory cortex. Significant initial reductions in responses were observed, yet a left-hemisphere bias and unequal weighting of inputs favoring the long-term deaf ear did not converge to a balanced state observed in the binaurally developed system. Bilateral response enhancement was significantly reduced in left auditory cortex suggesting deficits in ipsilateral response inhibition of new, dominant, inputs during bilateral processing. These findings paradoxically demonstrate the adaptive capacity of the adolescent auditory system beyond an early sensitive period for bilateral input, as well as restrictions on its potential to fully reverse cortical imbalances driven by long-term unilateral deafness

Design and use of novel non-invasive head immobilisation method for investigation of behavioural and functional asymmetries in non-human primate auditory cortex

PhD ThesisThis project was initiated with two goals in mind. The first, to refine methods of head immobilisation for rhesus macaques participating in experiments which do not require direct access to the brain, and the second to investigate the effect of attention on lateralisation in auditory cortex. Head immobilisation is often necessary for neuroscientific procedures. A number of Non-invasive Head Immobilisation Systems (NHIS) for monkeys are available, but the need remains for a feasible integrated system combining a broad range of essential features. This thesis details the development of an individually customised macaque NHIS which addresses several animal welfare and scientific needs. The system comprises a customised facemask that can be used separately or combined with a back piece to form a full head helmet. The system was evaluated during performance on several auditory or visual behavioural tasks with testing sessions lasting 1.5-2hrs. To investigate the effect of attention on lateralised processes, four male rhesus macaques were trained to perform an active auditory spatial discrimination task (two of which used the NHIS) using either conspecific “coo” vocalisations or a coo vocalisation from a different individual which had the phase information scrambled, but preserved the spectral components (sCoo). Behavioural results indicated a directional bias during the task with coos, with the animals performing the task with ease when the coo initially appeared on the left but performance being hindered when the coo first appeared on the right. No bias was observed with an animal initially trained with the noise. Attention effects on hemispheric laterality were then studied using fMRI with the trained animals and, as a point of reference, a naïve animal who was passively presented with the task stimuli. The results shown have implications for the control of attention when investigating lateralised processing in both human and non-human species. Additionally, it is conclusively shown that auditory fMRI and behavioural experiments can be conducted without the need for invasive head immobilisation techniques in rhesus macaques

The neuromodulatory properties of gonadal steroid hormones with regard to individual differences in cognition and brain organisation.

Sex hormones exert powerful modulatory effects throughout the nervous system and influence various aspects of behaviour. For example, estrogen and progesterone have been shown to influence sex-sensitive cognitive abilities, such as verbal and visuo-spatial abilities (Hampson, 1990a, 1990b). More recently it has been suggested that estradiol can influence executive functioning abilities, such as cognitive control, working memory and selective attention (Colzato et al., 2012; Hampson, 1990a, 1990b; Hampson & Morley, 2013; Hjelmervik et al., 2012; Rosenberg & Park, 2002). Sex hormones have also been shown to affect functional brain organisation, in particular, cerebral lateralisation. Cerebral lateralisation is a fundamental principle of functional brain organisation, referring to the asymmetrical representation of a specific cognitive process in a particular cerebral hemisphere. For example, the left hemisphere is typically dominant for language, while the right hemisphere is dominant for visuo-spatial processes in the healthy brain (Broca, 1861; Hellige, 1993; Kimura, 1967). While men typically demonstrate pronounced, stable patterns of lateralisation, women are assumed to be less lateralised and demonstrate a higher level of intra- and inter-individual variation in the degree of lateralisation (e.g., Bibawi et al, 1995; Cowell et al., 2011; Hampson, 1990a, 1990b; Hausmann et al., 2002; Hausmann & Güntürkün, 2000; Hjelmervik et al., 2012; Wadnerkar et al., 2008; Weis et al., 2008). The present thesis focuses on the influence of estrogen (particularly estradiol) and progesterone on cerebral lateralisation, functional connectivity, and cognition in naturally cycling women. Young, naturally cycling women, free of hormonal contraceptives, were tested during specific phases of their menstrual cycles across a series of behavioural studies and a resting state functional magnetic resonance imaging study. Hormone levels (estradiol and progesterone) were directly measured in each study. The results showed that while both cerebral lateralisation and executive functioning could be modulated by sex hormones, such effects may be smaller and more specific than previously suggested. Firstly, while estradiol (and progesterone) influenced language lateralisation, this effect was dependent on the degree of asymmetry produced by the task used. Specifically, a task that yields a large degree of asymmetry (presumably due to strong bottom-up effects) is likely to mask any sex hormonal effect on other processes underpinning lateralisation, such as interhemispheric inhibition. Secondly, and similarly, the effects of estradiol on executive function and cognitive control were smaller and more specific than previously demonstrated. As such, it was argued that estradiol effects on cognition are likely dependent upon individual differences in neurophysiology, such as those that underpin different levels of schizotypy. Finally, the rs-fMRI findings demonstrate that functional connectivity in the DMN fluctuates according to different phases of the menstrual cycle, while connectivity in the auditory network is stable. Taken together, the findings presented here highlight the extensive effects of sex hormones on the brain, and on behaviours beyond those related to sexual reproduction. Furthermore, they suggest that sex hormonal effects are more complex than previously hypothesised, underpinned by their capacity to interact with task demands, other hormones, and individual differences in neurophysiology