Biology subjects

Gander, P. E.

Publications and source records attributed to Gander, P. E..

14 recordsLinked to original sources

bioRxiv2025

Brain-wide single-neuron bases of working memory for sounds in humans

In order to understand the constantly changing acoustic world our brains must maintain elements of auditory scenes in memory. The neural mechanisms for this fundamental process remain unclear. Here, we report human intracranial recordings of 1269 single neurons while participants performed a non-verbal auditory working memory task that required adjustment of a tone frequency to match a target. We found neurons within hippocampus, insula and cingulate cortex, for which firing rates were modulated at different phases of the task, particularly during maintenance and adjustment. For the majority of the neurons modulated during maintenance there was a striking suppression of activity rather than increased activity. Across the entire neuronal population, state-space analysis demonstrated attractor-like states corresponding to different task phases. Behaviorally, more neurons were modulated at the beginning of the maintenance phase in trials when participants performed better. State-space analysis was consistent with greater attractor-like activity during the adjustment phase supporting better performance. These data support the existence of a widely distributed neural code for auditory working memory that determines related behavior based on attractor-like states.

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bioRxiv2025

Perceptual Novelty in Tinnitus a Causative Factor for its Persistence. A Stimulus Novelty Based P300 Paradigm on Acute, Chronic, and Non-Tinnitus Controls

Our understanding of tinnitus pathophysiology may be greatly advanced by understanding how the condition evolves from its initial onset or acute stage to its chronic manifestation. Such a transition likely reflects dynamic neurophysiological changes within central auditory and non-auditory networks. Previous studies have highlighted that individuals with acute tinnitus tend to have increased activity in the regions of anterior cingulate cortex, inferior parietal lobe, and insula all of which are essential in constituting the salience network. We therefore aimed at tapping into the salience network of tinnitus through a novelty based P300 paradigm in individuals with Acute, Post Acute (six months follow up since tinnitus onset) Chronic, and Controls. Participants were presented with an auditory oddball paradigm comprising three deviant types: (1) novel environmental sounds, (2) low-frequency tonal deviants, and (3) high-frequency tonal deviants, embedded within a sequence of frequent standard tones. Our results indicate a significant drop in P300 amplitude during the Post Acute stage across the three deviant stimuli, highlighting the substantial influence of the anterior cingulate cortex/salience network in possible generation of tinnitus and inferior parietal lobe in the persistence of tinnitus.

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bioRxiv2025

Evidence for a Transient State of Auditory Hypersensitivity During Initial Onset of Tinnitus, Evidenced by Intensity Dependence of the Auditory Evoked Potential (IDAEP)

Our understanding of tinnitus pathophysiology may be greatly advanced by understanding how the condition evolves from its initial onset or acute stage to its chronic manifestation. Such a transition likely reflects dynamic neurophysiological changes within central auditory and non-auditory networks. Our integrated model of tinnitus posits that sensory precision (sensory weighting) may be heightened during the acute stages of tinnitus to resolve degraded auditory input, but in chronic tinnitus, its role may diminish as plastic processes take over the percepts maintenance. Consequently, we hypothesize that bottom-up neural mechanisms linked to initiation of tinnitus, such as central gain and neural synchrony, are maximal around the time of tinnitus onset, but later subside by way of regression to the mean. We evaluated this hypothesis by measuring central auditory reactivity through the Intensity Dependence of Auditory Evoked Potential (IDAEP), a non-invasive index of higher-order inhibitory processing within the auditory system. A steeper IDAEP slope is associated with heightened sensory reactivity (higher sensitivity to changes in auditory stimuli), indicative of reduced central inhibition. Conversely, a shallower slope reflects greater inhibitory control. Studying a group with acute tinnitus (onset within six weeks), with a repeated assessment after six months from onset, we found an initially increased IDAEP slope in the acute stage, which had significantly reduced at follow-up, supporting our hypothesis that there is increased sensory reactivity during tinnitus onset, which need not persist in order for tinnitus to become chronic.

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bioRxiv2025

Brain bases for navigating acoustic features

Whether physical navigation shares neural substrates with mental travel in other behaviourally relevant domains is debated. With respect to sound, pure-tone working memory in humans elicits hippocampal as well as auditory cortical and inferior frontal activity, and rodent work suggests that hippocampal cells that usually track an animals physical location can also map to tone frequency when task-relevant. We generated a sound dimension based on the density of random-frequency tones in a stack, resulting in a percept ranging from low- ("beepy") to high-density ("noisy"). We established that unlike tone frequency, which listeners automatically associate with vertical position, this density dimension elicited no consistent spatial mapping. During functional magnetic resonance imaging, human participants held in mind the density of a series of tone stacks and, after a short maintenance period, adjusted further stacks to match the target ("navigation"). Density of the currently heard sound was represented most strongly in bilateral non-primary auditory cortex, specifically bilateral planum polare, while density of the maintained target was represented in right anterior hippocampus and left inferior temporal gyrus. Encoding and maintenance activity in bilateral hippocampus, inferior frontal gyrus, planum polare and posterior cingulate was positively associated with subsequent navigation success. Bilateral inferior frontal gyrus and hippocampus were among regions with elevated activity during adjustment, compared to a parity-judgment condition with closely matched acoustics and motor demands. Bilateral orbitofrontal cortex was more active when navigation was toward a target density than when participants adjusted density in a control condition with no particular target. We find that self-initiated travel along a non-spatial auditory dimension engages a brain system overlapping with that supporting physical navigation. Key PointsO_LIWork in rodents suggests that navigation in physical space and the active analysis of sounds share a neural substrate in the hippocampus, supporting the use of common computational mechanisms. C_LIO_LIWe examined the human brain system for navigation through an acoustic environment to a remembered target. C_LIO_LIIn addition to high-level auditory cortex we demonstrate involvement of the hippocampus in acoustic navigation along with other sites in frontal and cingulate cortex that also support physical navigation. C_LI

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bioRxiv2023

Exercise modulates human hippocampal-cortical ripple dynamics

Physical exercise acutely improves hippocampus-dependent memory. Whereas animal studies have offered cellular- and synaptic-level accounts of these effects, human neuroimaging studies show that exercise improves hippocampal-cortical connectivity at the macroscale level. However, the neurophysiological basis of exercise-induced effects on hippocampal-cortical circuits remains unknown. Experimental evidence supports that hippocampal sharp wave-ripples (SWR) play a critical role in learning and memory. Coupling between SWRs in the hippocampus and neocortex may reflect modulations in inter-regional connectivity required by mnemonic processes. Here, we examine the hypothesis that exercise modulates hippocampal-cortical ripple dynamics in the human brain. We performed intracranial recordings in epilepsy patients undergoing pre-surgical evaluation, during awake resting state, before and after an exercise session. Exercise increased ripple rate in the hippocampus. Exercise also enhanced the coupling and phase-synchrony between cortical ripples in the limbic and the default mode (DM) cortical networks and hippocampal SWRs. Further, higher heart rate during exercise, reflecting exercise intensity, was related to a subsequent increase in resting state ripples across specific cortical networks including the DMN. These results offer the first direct evidence that a single exercise session elicits changes in ripple events, a well-established neurophysiological marker of mnemonic processing. The characterization and anatomical distribution of the described modulation points to hippocampal ripples as a potential mechanism by which exercise elicits its reported short-term effects in cognition.

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bioRxiv2023

Temporally organized representations of reward and risk in the human brain

AO_SCPLOWBSTRACTC_SCPLOWThe value and uncertainty associated with choice alternatives constitute critical features along which decisions are made. While the neural substrates supporting reward and risk processing have been investigated, the temporal organization by which these computations are encoded remains elusive. Here we leverage the high spatiotemporal precision of intracranial electroencephalography (iEEG) to uncover how representations of decision-related computations unfold in time. We present evidence of locally distributed representations of reward and risk variables that are temporally organized across multiple regions of interest. Reward outcome representations across wide-spread regions follow a temporally cascading order along the anteroposterior axis of the brain. In contrast, expected value can be decoded from multiple regions at the same time, and error signals in both reward and risk domains reflect a mixture of sequential and parallel encoding. We highlight the role of the anterior insula in generalizing between reward prediction error (RePE) and risk prediction error (RiPE), within which the encoding of RePE in the distributed iEEG signal predicts RiPE. Together our results emphasize the utility of uncovering temporal dynamics in the human brain for understanding how computational processes critical for value-based decisions under uncertainty unfold.

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bioRxiv2022

Immediate neural network impact after the loss of a semantic hub

The human brain extracts meaning from the world using an extensive neural system for semantic knowledge. Whether such broadly distributed systems1-3 crucially depend on or can compensate for the loss of one of their highly interconnected hubs4-6 is controversial4. The strongest level of causal evidence for the role of a brain hub is to evaluate its acute network-level impact following disconnection and any rapid functional compensation that ensues. We report rare neurophysiological data from two patients who underwent awake intracranial recordings during a speech prediction task immediately before and after neurosurgical treatment that required disconnection of the left anterior temporal lobe (ATL), a crucial hub for semantic knowledge4-6. Informed by a predictive coding framework, we tested three sets of hypotheses including diaschisis causing disruption in interconnected sites7 and incomplete or complete compensation by other language-critical and speech processing sites8-10. Immediately after ATL disconnection, we observed highly specific neurophysiological alterations in the recorded fronto-temporal network, including abnormally magnified high gamma responses to the speech sounds in auditory cortex. We also observed evidence for rapid compensation, seen as focal increases in effective connectivity involving language-critical sites in the inferior frontal gyrus and speech processing sites in auditory cortex. However, compensation was incomplete, in part because after ATL disconnection speech prediction signals were depleted in auditory cortex. This study provides direct causal evidence for a semantic hub in the human brain and shows striking neural impact and a rapid attempt at compensation in a neural network after the loss of one of its hubs.

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bioRxiv2022

Effects of transcranial magnetic stimulation on the human brain recorded with intracranial electrocorticography: First-in-human study

Transcranial magnetic stimulation (TMS) is increasingly used as a noninvasive technique for neuromodulation in research and clinical applications, yet its mechanisms are not well understood. Here, we present the first in-human study evaluating the effects of TMS using intracranial electrocorticography (iEEG) in neurosurgical patients. We first evaluated safety in a gel-based phantom. We then performed TMS-iEEG in 20 neurosurgical participants with no adverse events. Next, we evaluated brain-wide intracranial responses to single pulses of TMS to the dorsolateral prefrontal cortex (dlPFC) (N=10, 1414 electrodes). We demonstrate that TMS preferentially induces neuronal responses locally within the dlPFC at sites with higher electric field strength. Evoked responses were also noted downstream in the anterior cingulate and anterior insular cortex, regions functionally connected to the dlPFC. These findings support the safety and promise of TMS-iEEG in humans to examine local and network-level effects of TMS with higher spatiotemporal resolution than currently available methods.

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bioRxiv2021

Distribution of multi-unit pitch responses recorded intracranially from human auditory cortex

The perception of pitch requires the abstraction of stimulus properties related to the spectrotemporal structure of sound. Previous studies utilizing both animal electrophysiology and human imaging have indicated the presence of a center for pitch representation in the auditory cortex. Recent data from our own group - examining local field potentials (LFPs) in humans - indicate more widely distributed pitch-associated responses within the auditory cortex (Gander et al., 2019). To probe this with greater spatial resolution, we examined multi-unit activity related to three different auditory stimuli, in seven epilepsy patients who were implanted with high-impedance electrodes in auditory cortex for the clinical purpose of localizing seizures. The stimuli were regular-interval noise (RIN) with a pitch strength that is related to the temporal regularity, and pitch value determined by repetition rate, and harmonic complexes with missing fundamentals. We demonstrated increases in spiking activity in 69 of 104 (66%) responsive multiunit activity in auditory cortex due to pitch-associated stimuli. Importantly, these responses were distributed across the entire extent of Heschls gyrus (HG), in both primary and non-primary areas, rather than isolated to a specific region, and this finding was evident regardless of the stimulus presented. These findings are the first multi-unit pitch responses recorded from humans, and align with a recent study in macaques (Kikuchi et al., 2019) demonstrating that both local field potential and unit responses to pitch-inducing stimuli are distributed throughout auditory cortex. Significance StatementThe perception of pitch is a fundamental acoustic attribute that is mediated by the auditory system. Despite its importance, there is still debate as to the precise areas responsible for its encoding, which may be due to differences in the recording measures and choices of stimuli used in previous studies. Here, we present the first study to measure multi-unit pitch responses in the auditory cortices of intracranially-implanted humans. Importantly, we demonstrate reliable responses to three different pitch-inducing paradigms that are distributed throughout Heschls gyrus, rather than being localized to a particular region. These data provide a bridge across animal and human studies, and aid in our understanding of the processing of a critical attribute of acoustic stimuli.

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bioRxiv2021

Neural correlates of individual differences in speech-in-noise performance in a large cohort of cochlear implant users

ObjectivesUnderstanding speech in noise (SiN) is a complex task that recruits multiple cortical subsystems. Individuals vary in their ability to understand SiN. This cannot be explained by simple peripheral hearing profiles, but recent work by our group (Kim et al., 2021, Neuroimage) highlighted central neural factors underlying the variance in SiN ability in normal hearing (NH) subjects. The current study examined neural predictors of speech-in-noise ability in a large cohort of cochlear-implant (CI) users, with the long-term goal of developing a simple electrophysiological correlate that could be implemented in clinics. DesignWe recorded electroencephalography (EEG) in 114 post-lingually deafened CI users while they completed the California Consonant Test (CCT): a word-in-noise task. In many subjects, data were also collected on two other commonly used clinical measures of speech perception: a word-in-quiet task (Consonant-Nucleus-Consonant [CNC]) word and a sentence-in-noise task (AzBio sentences). Neural activity was assessed at a single vertex electrode (Cz), to maximize generalizability to clinical situations. The N1-P2 complex of event-related potentials (ERPs) at this location were included in multiple linear regression analyses, along with several other demographic and hearing factors as predictors of speech in noise performance. ResultsIn general, there was a good agreement between the scores on the three speech perception tasks. ERP amplitudes did not predict AzBio performance which was predicted by the duration of device use, low-frequency hearing thresholds, and age. However, ERP amplitudes were strong predictors for performance for both word recognition tasks: the CCT (which was conducted simultaneously with EEG recording), and the CNC (conducted offline). These correlations held even after accounting for known predictors of performance including residual low-frequency hearing thresholds. In CI-users, better performance was predicted by an increased cortical response to the target word, in contrast to previous reports in normal-hearing subjects in whom speech perception ability was accounted for by the ability to suppress noise. ConclusionsThese data indicate a neurophysiological correlate of speech-in-noise performance that can be relatively easily captured within the clinic, thereby revealing a richer profile of an individuals hearing performance than shown by psychoacoustic measures alone. These results also highlight important differences between sentence and word recognition measures of performance and suggest that individual differences in these measures may be underwritten by different mechanisms. Finally, the contrast with prior reports of NH listeners in the same task suggests CI-users performance may be explained by a different weighting of neural processes than NH listeners.

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bioRxiv2020

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 Heschls 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. The work demonstrates sustained activity patterns that can only be explained by AWM maintenance, with prominent low-frequency increases in medial temporal lobe regions.

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bioRxiv2020

Differential causal involvement of human auditory and frontal cortices in vocal motor control

Speech motor control requires integration of sensory and motor information. Bidirectional communication between frontal and auditory cortices is crucial for speech production, self-monitoring and motor control. We used cortical direct electrical stimulation (DES) to functionally dissect audio-motor interactions underlying speech production and motor control. Eleven neurosurgical patients performed a visually cued vocal task in which a short auditory feedback perturbation was introduced during vocalization. We evaluated the effect of DES on vocal initiation, voice fundamental frequency (F0) and feedback-dependent motor control. DES of frontal sites modulated vocal onset latencies. Stimulation of different inferior frontal gyrus sites elicited either shortening or prolongation of vocal latencies. DES distinctly modulated voice F0 at different vocalization stages. Frontal and temporal areas played an important role in setting voice F0 in the first 250 ms of an utterance, while Heschls gyrus was involved later when auditory input is available for self-monitoring. Vocal responses to pitch-shifted auditory feedback were mostly reduced by DES of non-core auditory cortices. Overall, we demonstrate that vocal planning and initiation are driven by frontal cortices, while feedback-dependent control relies predominantly on non-core auditory cortices. Our findings represent direct evidence of the role played by different auditory and frontal regions in vocal motor control.

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bioRxiv2019

External and Internal Signal-to-noise Ratios Alter Timing and Location of Cortical Activities During Speech-in-noise Perception

Understanding speech in noise (SiN) is a complex task that recruits multiple cortical subsystems. There is a variance in individuals ability to understand SiN that cannot be explained by simple hearing profiles, which suggests that central factors may underlie the variance in SiN ability. Here, we elucidated a few cortical functions involved during a SiN task and their contributions to individual variance using both within- and across-subject approaches. Through our within-subject analysis of source-localized electroencephalography, we investigated how acoustic signal-to-noise ratio (SNR) alters cortical evoked responses to a target word across the speech recognition areas, finding stronger responses in left supramarginal gyrus (SMG, BA40 the dorsal lexicon area) with quieter noise. Through an individual differences approach, we found that listeners show different neural sensitivity to the background noise and target speech, reflected in the amplitude ratio of earlier auditory-cortical responses to speech and noise, named as an internal SNR. Listeners with better internal SNR showed better SiN performance. Further, we found that the post-speech time SMG activity explains a further amount of variance in SiN performance that is not accounted for by internal SNR. This result demonstrates that at least two cortical processes contribute to SiN performance independently: pre-target time processing to attenuate neural representation of background noise and post-target time processing to extract information from speech sounds.

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bioRxiv2019

A sound-sensitive source of alpha oscillations in human non-primary auditory cortex

The functional organization of human auditory cortex can be probed by characterizing responses to various classes of sound at different anatomical locations. Along with histological studies this approach has revealed a primary field in posteromedial Heschls gyrus (HG) with pronounced induced high-frequency (70-150 Hz) activity and short-latency responses that phase-lock to rapid transient sounds. Low-frequency neural oscillations are also relevant to stimulus processing and information flow, however their distribution within auditory cortex has not been established. Alpha activity (7-14 Hz) in particular has been associated with processes that may differentially engage earlier versus later levels of the cortical hierarchy, including functional inhibition and the communication of sensory predictions. These theories derive largely from the study of occipitoparietal sources readily detectable in scalp electroencephalography. To characterize the anatomical basis and functional significance of less accessible temporal-lobe alpha activity we analyzed responses to sentences in seven human adults (four female) with epilepsy who had been implanted with electrodes in superior temporal cortex. In contrast to primary cortex in posteromedial HG, a non-primary field in anterolateral HG was characterized by high spontaneous alpha activity that was strongly suppressed during auditory stimulation. Alpha-power suppression decreased with distance from anterolateral HG throughout superior temporal cortex, and was more pronounced for clear compared to degraded speech. This suppression could not be accounted for solely by a change in the slope of the power spectrum. The differential manifestation and stimulus-sensitivity of alpha oscillations across auditory fields should be accounted for in theories of their generation and function.\n\nSignificance StatementTo understand how auditory cortex is organized in support of perception, we recorded from patients implanted with electrodes for clinical reasons. This allowed measurement of activity in brain regions at different levels of sensory processing. Oscillations in the alpha range (7-14 Hz) have been associated with functions including sensory prediction and inhibition of regions handling irrelevant information, but their distribution within auditory cortex is not known. A key finding was that these oscillations dominated in one particular non-primary field, anterolateral Heschls gyrus, and were suppressed when subjects listened to sentences. These results build on our knowledge of the functional organization of auditory cortex and provide anatomical constraints on theories of the generation and function of alpha oscillations.

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