Neural phase locking predicts BOLD response in human auditory cortex

Natural environments elicit both phase-locked and non-phase-locked neural responses to the stimulus in the brain. The interpretation of the BOLD signal to date has been based on an association of the non-phase-locked power of high-frequency local field potentials (LFPs), or the related spiking activity in single neurons or groups of neurons. Previous studies have not examined the prediction of the BOLD signal by phase-locked responses. We examined the relationship between the BOLD response and LFPs in the same nine human subjects from multiple corresponding points in the auditory cortex, using amplitude modulated pure tone stimuli of a duration to allow an analysis of phase locking of the sustained time period without contamination from the onset response. The results demonstrate that both phase locking at the modulation frequency and its harmonics, and the oscillatory power in gamma/high-gamma bands are required to predict the BOLD response. Biophysical models of BOLD signal generation in auditory cortex therefore require revision and the incorporation of both phase locking to rhythmic sensory stimuli and power changes in the ensemble neural activity

Neural phase locking predicts BOLD response in human auditory cortex

Natural environments elicit both phase-locked and non-phase-locked neural responses to the stimulus in the brain. The interpretation of the BOLD signal to date has been based on an association of the non-phase-locked power of high-frequency local field potentials (LFPs), or the related spiking activity in single neurons or groups of neurons. Previous studies have not examined the prediction of the BOLD signal by phase-locked responses. We examined the relationship between the BOLD response and LFPs in the same nine human subjects from multiple corresponding points in the auditory cortex, using amplitude modulated pure tone stimuli of a duration to allow an analysis of phase locking of the sustained time period without contamination from the onset response. The results demonstrate that both phase locking at the modulation frequency and its harmonics, and the oscillatory power in gamma/high-gamma bands are required to predict the BOLD response. Biophysical models of BOLD signal generation in auditory cortex therefore require revision and the incorporation of both phase locking to rhythmic sensory stimuli and power changes in the ensemble neural activity

Oscillatory correlates of auditory working memory examined with human electrocorticography

This work examines how sounds are held in auditory working memory (AWM) in humans by examining oscillatory local field potentials (LFPs) in candidate brain regions. Previous fMRI studies by our group demonstrated blood oxygenation level-dependent (BOLD) response increases during maintenance in auditory cortex, inferior frontal cortex and the hippocampus using a paradigm with a delay period greater than 10s. The relationship between such BOLD changes and ensemble activity in different frequency bands is complex, and the long delay period raised the possibility that long-term memory mechanisms were engaged. Here we assessed LFPs in different frequency bands in six subjects with recordings from all candidate brain regions using a paradigm with a short delay period of 3 s. Sustained delay activity was demonstrated in all areas, with different patterns in the different areas. Enhancement in low frequency (delta) power and suppression across higher frequencies (beta/ gamma) were demonstrated in primary auditory cortex in medial Heschl’s gyrus (HG) whilst non-primary cortex showed patterns of enhancement and suppression that altered at different levels of the auditory hierarchy from lateral HG to superior- and middle-temporal gyrus. Inferior frontal cortex showed increasing suppression with increasing frequency. The hippocampus and parahippocampal gyrus showed low frequency increases and high frequency decreases in oscillatory activity. This work demonstrates sustained activity patterns during AWM maintenance, with prominent low-frequency increases in medial temporal lobe regions

Common Fronto-temporal Effective Connectivity in Humans and Monkeys

Cognitive pathways supporting human language and declarative memory are thought to have uniquely evolutionarily differentiated in our species. However, cross-species comparisons are missing on site-specific effective connectivity between regions important for cognition. We harnessed a new approach using functional imaging to visualize the impact of direct electrical brain stimulation in human neurosurgery patients. Applying the same approach with macaque monkeys, we found remarkably comparable patterns of effective connectivity between auditory cortex and ventro-lateral prefrontal cortex (vlPFC) and parahippocampal cortex in both species. Moreover, in humans electrical tractography revealed rapid evoked potentials in vlPFC from stimulating auditory cortex and speech sounds drove vlPFC, consistent with prior evidence in monkeys of direct projections from auditory cortex to vocalization responsive regions in vlPFC. The results identify a common effective connectivity signature that from auditory cortex is equally direct to vlPFC and indirect to the hippocampus (via parahippocampal cortex) in human and nonhuman primates

Cortical and subcortical speech-evoked responses in young and older adults: Effects of background noise, arousal states, and neural excitability

This thesis investigated how the brain processes speech signals in human adults across a wide age-range in the sensory auditory systems using electroencephalography (EEG). Two types of speech-evoked phase-locked responses were focused on: (i) cortical responses (theta-band phase-locked responses) that reflect processing of low-frequency slowly-varying envelopes of speech; (ii) subcortical/peripheral responses (frequency-following responses; FFRs) that reflect encoding of speech periodicity and temporal fine structure information. The aims are to elucidate how these neural activities are affected by different internal (aging, hearing loss, level of arousal and neural excitability) and external (background noise) factors during our daily life through three studies. Study 1 investigated theta-band phase-locking and FFRs in noisy environments in young and older adults. It investigated how aging and hearing loss affect these activities under quiet and noisy environments, and how these activities are associated with speech-in-noise perception. The results showed that ageing and hearing loss affect speech-evoked phase-locked responses through different mechanisms, and the effects of aging on cortical and subcortical activities take different roles in speech-in-noise perception. Study 2 investigated how level of arousal, or consciousness, affects phase-locked responses in young and older adults. The results showed that both theta-band phase-locking and FFRs decreases following decreases in the level of arousal. It was further found that neuro-regulatory role of sleep spindles on theta-band phase-locking is distinct between young and older adults, indicating that the mechanisms of neuro-regulation for phase-locked responses in different arousal states are age-dependent. Study 3 established a causal relationship between the auditory cortical excitability and FFRs using combined transcranial direct current stimulation (tDCS) and EEG. FFRs were measured before and after tDCS was applied over the auditory cortices. The results showed that changes in neural excitability of the right auditory cortex can alter FFR magnitudes along the contralateral pathway. This shows important theoretical and clinical implications that causally link functions of auditory cortex with neural encoding of speech periodicity. Taken together, findings of this thesis will advance our understanding of how speech signals are processed via neural phase-locking in our everyday life across the lifespan