Improved Speech Hearing in Noise with Invasive Electrical Brain Stimulation.

Speech perception in noise is a challenging everyday task with which many listeners have difficulty. Here, we report a case in which electrical brain stimulation of implanted intracranial electrodes in the left planum temporale (PT) of a neurosurgical patient significantly and reliably improved subjective quality (up to 50%) and objective intelligibility (up to 97%) of speech in noise perception. Stimulation resulted in a selective enhancement of speech sounds compared with the background noises. The receptive fields of the PT sites whose stimulation improved speech perception were tuned to spectrally broad and rapidly changing sounds. Corticocortical evoked potential analysis revealed that the PT sites were located between the sites in Heschl's gyrus and the superior temporal gyrus. Moreover, the discriminability of speech from nonspeech sounds increased in population neural responses from Heschl's gyrus to the PT to the superior temporal gyrus sites. These findings causally implicate the PT in background noise suppression and may point to a novel potential neuroprosthetic solution to assist in the challenging task of speech perception in noise.SIGNIFICANCE STATEMENT Speech perception in noise remains a challenging task for many individuals. Here, we present a case in which the electrical brain stimulation of intracranially implanted electrodes in the planum temporale of a neurosurgical patient significantly improved both the subjective quality (up to 50%) and objective intelligibility (up to 97%) of speech perception in noise. Stimulation resulted in a selective enhancement of speech sounds compared with the background noises. Our local and network-level functional analyses placed the planum temporale sites in between the sites in the primary auditory areas in Heschl's gyrus and nonprimary auditory areas in the superior temporal gyrus. These findings causally implicate planum temporale in acoustic scene analysis and suggest potential neuroprosthetic applications to assist hearing in noise.

Functional characterization of human Heschl's gyrus in response to natural speech.

Heschl's gyrus (HG) is a brain area that includes the primary auditory cortex in humans. Due to the limitations in obtaining direct neural measurements from this region during naturalistic speech listening, the functional organization and the role of HG in speech perception remain uncertain. Here, we used intracranial EEG to directly record neural activity in HG in eight neurosurgical patients as they listened to continuous speech stories. We studied the spatial distribution of acoustic tuning and the organization of linguistic feature encoding. We found a main gradient of change from posteromedial to anterolateral parts of HG. We also observed a decrease in frequency and temporal modulation tuning and an increase in phonemic representation, speaker normalization, speech sensitivity, and response latency. We did not observe a difference between the two brain hemispheres. These findings reveal a functional role for HG in processing and transforming simple to complex acoustic features and inform neurophysiological models of speech processing in the human auditory cortex.

Inducing neuroplasticity through intracranial θ-burst stimulation in the human sensorimotor cortex.

The progress of therapeutic neuromodulation greatly depends on improving stimulation parameters to most efficiently induce neuroplasticity effects. Intermittent θ-burst stimulation (iTBS), a form of electrical stimulation that mimics natural brain activity patterns, has proved to efficiently induce such effects in animal studies and rhythmic transcranial magnetic stimulation studies in humans. However, little is known about the potential neuroplasticity effects of iTBS applied through intracranial electrodes in humans. This study characterizes the physiological effects of intracranial iTBS in humans and compare them with α-frequency stimulation, another frequently used neuromodulatory pattern. We applied these two stimulation patterns to well-defined regions in the sensorimotor cortex, which elicited contralateral hand muscle contractions during clinical mapping, in patients with epilepsy implanted with intracranial electrodes. Treatment effects were evaluated using oscillatory coherence across areas connected to the treatment site, as defined with corticocortical-evoked potentials. Our results show that iTBS increases coherence in the ß-frequency band within the sensorimotor network indicating a potential neuroplasticity effect. The effect is specific to the sensorimotor system, the ß band, and the stimulation pattern and outlasted the stimulation period by ∼3 min. The effect occurred in four out of seven subjects depending on the buildup of the effect during iTBS treatment and other patterns of oscillatory activity related to ceiling effects within the ß band and to preexistent coherence within the α band. By characterizing the neurophysiological effects of iTBS within well-defined cortical networks, we hope to provide an electrophysiological framework that allows clinicians/researchers to optimize brain stimulation protocols which may have translational value.NEW & NOTEWORTHY θ-Burst stimulation (TBS) protocols in transcranial magnetic stimulation studies have shown improved treatment efficacy in a variety of neuropsychiatric disorders. The optimal protocol to induce neuroplasticity in invasive direct electrical stimulation approaches is not known. We report that intracranial TBS applied in human sensorimotor cortex increases local coherence of preexistent ß rhythms. The effect is specific to the stimulation frequency and the stimulated network and outlasts the stimulation period by ∼3 min.

Intracortical Dynamics Underlying Repetitive Stimulation Predicts Changes in Network Connectivity.

Targeted stimulation can be used to modulate the activity of brain networks. Previously we demonstrated that direct electrical stimulation produces predictable poststimulation changes in brain excitability. However, understanding the neural dynamics during stimulation and its relationship to poststimulation effects is limited but critical for treatment optimization. Here, we applied 10 Hz direct electrical stimulation across several cortical regions in 14 human subjects (6 males) implanted with intracranial electrodes for seizure monitoring. The stimulation train was characterized by a consistent increase in high gamma (70-170 Hz) power. Immediately post-train, low-frequency (1-8 Hz) power increased, resulting in an evoked response that was highly correlated with the neural response during stimulation. Using two measures of network connectivity, corticocortical evoked potentials (indexing effective connectivity), and theta coherence (indexing functional connectivity), we found a stronger response to stimulation in regions that were highly connected to the stimulation site. In these regions, repeated cycles of stimulation trains and rest progressively altered the stimulation response. Finally, after just 2 min (∼10%) of repetitive stimulation, we were able to predict poststimulation connectivity changes with high discriminability. Together, this work reveals a relationship between stimulation dynamics and poststimulation connectivity changes in humans. Thus, measuring neural activity during stimulation can inform future plasticity-inducing protocols.SIGNIFICANCE STATEMENT Brain stimulation tools have the potential to revolutionize the treatment of neuropsychiatric disorders. Despite the widespread use of brain stimulation techniques such as transcranial magnetic stimulation, the therapeutic efficacy of these technologies remains suboptimal. This is in part because of a lack of understanding of the dynamic neural changes that occur during stimulation. In this study, we provide the first detailed characterization of neural activity during plasticity induction through intracranial electrode stimulation and recording in 14 medication-resistant epilepsy patients. These results fill a missing gap in our understanding of stimulation-induced plasticity in humans. In the longer-term, these data will also guide our translational efforts toward non-invasive, personalized, closed-loop neuromodulation therapy for neurological and psychiatric disorders in humans.

Induction and Quantification of Excitability Changes in Human Cortical Networks.

How does human brain stimulation result in lasting changes in cortical excitability? Uncertainty on this question hinders the development of personalized brain stimulation therapies. To characterize how cortical excitability is altered by stimulation, we applied repetitive direct electrical stimulation in eight human subjects (male and female) undergoing intracranial monitoring. We evaluated single-pulse corticocortical-evoked potentials (CCEPs) before and after repetitive stimulation across prefrontal (n = 4), temporal (n = 1), and motor (n = 3) cortices. We asked whether a single session of repetitive stimulation was sufficient to induce excitability changes across distributed cortical sites. We found a subset of regions at which 10 Hz prefrontal repetitive stimulation resulted in both potentiation and suppression of excitability that persisted for at least 10 min. We then asked whether these dynamics could be modeled by the prestimulation connectivity profile of each subject. We found that cortical regions (1) anatomically close to the stimulated site and (2) exhibiting high-amplitude CCEPs underwent changes in excitability following repetitive stimulation. We demonstrate high accuracy (72-95%) and discriminability (81-99%) in predicting regions exhibiting changes using individual subjects' prestimulation connectivity profile, and show that adding prestimulation connectivity features significantly improved model performance. The same features predicted regions of modulation following motor and temporal cortices stimulation in an independent dataset. Together, baseline connectivity profile can be used to predict regions susceptible to brain changes and provides a basis for personalizing brain stimulation.SIGNIFICANCE STATEMENT Brain stimulation is increasingly used to treat neuropsychiatric disorders by inducing excitability changes at specific brain regions. However, our understanding of how, when, and where these changes are induced is critically lacking. We inferred plasticity in the human brain after applying electrical stimulation to the brain's surface and measuring changes in excitability. We observed excitability changes in regions anatomically and functionally closer to the stimulation site. Those in responsive regions were accurately predicted using a classifier trained on baseline brain network characteristics. Finally, we showed that the excitability changes can potentially be monitored in real-time. These results begin to fill basic gaps in our understanding of stimulation-induced brain dynamics in humans and offer pathways to optimize stimulation protocols.

Breathing above the brain stem: volitional control and attentional modulation in humans.

Whereas the neurophysiology of respiration has traditionally focused on automatic brain stem processes, higher brain mechanisms underlying the cognitive aspects of breathing are gaining increasing interest. Therapeutic techniques have used conscious control and awareness of breathing for millennia with little understanding of the mechanisms underlying their efficacy. Using direct intracranial recordings in humans, we correlated cortical and limbic neuronal activity as measured by the intracranial electroencephalogram (iEEG) with the breathing cycle. We show this to be the direct result of neuronal activity, as demonstrated by both the specificity of the finding to the cortical gray matter and the tracking of breath by the gamma-band (40-150 Hz) envelope in these structures. We extend prior observations by showing the iEEG signal to track the breathing cycle across a widespread network of cortical and limbic structures. We further demonstrate a sensitivity of this tracking to cognitive factors by using tasks adapted from cognitive behavioral therapy and meditative practice. Specifically, volitional control and awareness of breathing engage distinct but overlapping brain circuits. During volitionally paced breathing, iEEG-breath coherence increases in a frontotemporal-insular network, and during attention to breathing, we demonstrate increased coherence in the anterior cingulate, premotor, insular, and hippocampal cortices. Our findings suggest that breathing can act as an organizing hierarchical principle for neuronal oscillations throughout the brain and detail mechanisms of how cognitive factors impact otherwise automatic neuronal processes during interoceptive attention. NEW & NOTEWORTHY Whereas the link between breathing and brain activity has a long history of application to therapy, its neurophysiology remains unexplored. Using intracranial recordings in humans, we show neuronal activity to track the breathing cycle throughout widespread cortical/limbic sites. Volitional pacing of the breath engages frontotemporal-insular cortices, whereas attention to automatic breathing modulates the cingulate cortex. Our findings imply a fundamental role of breathing-related oscillations in driving neuronal activity and provide insight into the neuronal mechanisms of interoceptive attention.

Joint population coding and temporal coherence link an attended talker's voice and location features in naturalistic multi-talker scenes.

Listeners readily extract multi-dimensional auditory objects such as a 'localized talker' from complex acoustic scenes with multiple talkers. Yet, the neural mechanisms underlying simultaneous encoding and linking of different sound features - for example, a talker's voice and location - are poorly understood. We analyzed invasive intracranial recordings in neurosurgical patients attending to a localized talker in real-life cocktail party scenarios. We found that sensitivity to an individual talker's voice and location features was distributed throughout auditory cortex and that neural sites exhibited a gradient from sensitivity to a single feature to joint sensitivity to both features. On a population level, cortical response patterns of both dual-feature sensitive sites but also single-feature sensitive sites revealed simultaneous encoding of an attended talker's voice and location features. However, for single-feature sensitive sites, the representation of the primary feature was more precise. Further, sites which selective tracked an attended speech stream concurrently encoded an attended talker's voice and location features, indicating that such sites combine selective tracking of an attended auditory object with encoding of the object's features. Finally, we found that attending a localized talker selectively enhanced temporal coherence between single-feature voice sensitive sites and single-feature location sensitive sites, providing an additional mechanism for linking voice and location in multi-talker scenes. These results demonstrate that a talker's voice and location features are linked during multi-dimensional object formation in naturalistic multi-talker scenes by joint population coding as well as by temporal coherence between neural sites. SIGNIFICANCE STATEMENT: Listeners effortlessly extract auditory objects from complex acoustic scenes consisting of multiple sound sources in naturalistic, spatial sound scenes. Yet, how the brain links different sound features to form a multi-dimensional auditory object is poorly understood. We investigated how neural responses encode and integrate an attended talker's voice and location features in spatial multi-talker sound scenes to elucidate which neural mechanisms underlie simultaneous encoding and linking of different auditory features. Our results show that joint population coding as well as temporal coherence mechanisms contribute to distributed multi-dimensional auditory object encoding. These findings shed new light on cortical functional specialization and multidimensional auditory object formation in complex, naturalistic listening scenes. HIGHLIGHTS: Cortical responses to an single talker exhibit a distributed gradient, ranging from sites that are sensitive to both a talker's voice and location (dual-feature sensitive sites) to sites that are sensitive to either voice or location (single-feature sensitive sites).Population response patterns of dual-feature sensitive sites encode voice and location features of the attended talker in multi-talker scenes jointly and with equal precision.Despite their sensitivity to a single feature at the level of individual cortical sites, population response patterns of single-feature sensitive sites also encode location and voice features of a talker jointly, but with higher precision for the feature they are primarily sensitive to.Neural sites which selectively track an attended speech stream concurrently encode the attended talker's voice and location features.Attention selectively enhances temporal coherence between voice and location selective sites over time.Joint population coding as well as temporal coherence mechanisms underlie distributed multi-dimensional auditory object encoding in auditory cortex.

Contribution of cholinergic and GABAergic mechanisms to direction tuning, discriminability, response reliability, and neuronal rate correlations in macaque middle temporal area.

Previous studies have investigated the effects of acetylcholine (ACh) on neuronal tuning, coding, and attention in primary visual cortex, but its contribution to coding in extrastriate cortex is unexplored. Here we investigate the effects of ACh on tuning properties of macaque middle temporal area MT neurons and contrast them with effects of gabazine, a GABA(A) receptor blocker. ACh increased neuronal activity, it had no effect on tuning width, but it significantly increased the direction discriminability of a neuron. Gabazine equally increased neuronal activity, but it widened tuning curves and decreased the direction discriminability of a neuron. Although gabazine significantly reduced response reliability, ACh application had little effect on response reliability. Finally, gabazine increased noise correlation of simultaneously recorded neurons, whereas ACh reduced it. Thus, both drugs increased firing rates, but only ACh application improved neuronal tuning and coding in line with effects seen in studies in which attention was selectively manipulated.

Interaction of bottom-up and top-down neural mechanisms in spatial multi-talker speech perception.

How the human auditory cortex represents spatially separated simultaneous talkers and how talkers' locations and voices modulate the neural representations of attended and unattended speech are unclear. Here, we measured the neural responses from electrodes implanted in neurosurgical patients as they performed single-talker and multi-talker speech perception tasks. We found that spatial separation between talkers caused a preferential encoding of the contralateral speech in Heschl's gyrus (HG), planum temporale (PT), and superior temporal gyrus (STG). Location and spectrotemporal features were encoded in different aspects of the neural response. Specifically, the talker's location changed the mean response level, whereas the talker's spectrotemporal features altered the variation of response around response's baseline. These components were differentially modulated by the attended talker's voice or location, which improved the population decoding of attended speech features. Attentional modulation due to the talker's voice only appeared in the auditory areas with longer latencies, but attentional modulation due to location was present throughout. Our results show that spatial multi-talker speech perception relies upon a separable pre-attentive neural representation, which could be further tuned by top-down attention to the location and voice of the talker.

Suppressive lateral interactions at parafoveal representations in primary visual cortex.

The perceptual salience and visibility of image elements is influenced by other elements in their vicinity. The perceptual effect of image elements on an adjacent target element depends on their relative orientation. Collinear flanking elements usually improve sensitivity for the target element, whereas orthogonal elements have a weaker effect. It is believed that the collinear flankers exert these effects through lateral interactions between neurons in the primary visual cortex (area V1), but the precise mechanisms underlying these contextual interactions remain unknown. Here, we directly examined this question by recording the effects of flankers on the responses of V1 neurons at parafoveal representations while monkeys performed a fixation task or a contrast detection task. We found, unexpectedly, that collinear flankers reduce the monkeys' perceptual sensitivity for a central target element. This behavioral effect was explained by a flanker-induced increase in the activity of V1 neurons in the absence of the central target stimulus, which reduced the amplitude of the target response. Our results indicate that the dominant effect of collinear flankers in parafoveal vision is suppression and suggest that these suppressive effects are caused by a decrease in the dynamic range of neurons coding the central target.