Dana Boatman-Reich

Language Mapping in Multilingual Patients: Electrocorticography and Cortical Stimulation During Naming

Multilingual patients pose a unique challenge when planning epilepsy surgery near language cortex because the cortical representations of each language may be distinct. These distinctions may not be evident with routine electrocortical stimulation mapping (ESM). Electrocorticography (ECoG) has recently been used to detect task-related spectral perturbations associated with functional brain activation. We hypothesized that using broadband high gamma augmentation (HGA, 60–150 Hz) as an index of cortical activation, ECoG would complement ESM in discriminating the cortical representations of first (L1) and second (L2) languages. We studied four adult patients for whom English was a second language, in whom subdural electrodes (a total of 358) were implanted to guide epilepsy surgery. Patients underwent ECoG recordings and ESM while performing the same visual object naming task in L1 and L2. In three of four patients, ECoG found sites activated during naming in one language but not the other. These language-specific sites were not identified using ESM. In addition, ECoG HGA was observed at more sites during L2 versus L1 naming in two patients, suggesting that L2 processing required additional cortical resources compared to L1 processing in these individuals. Post-operative language deficits were identified in three patients (one in L2 only). These deficits were predicted by ECoG spectral mapping but not by ESM. These results suggest that pre-surgical mapping should include evaluation of all utilized languages to avoid post-operative functional deficits. Finally, this study suggests that ECoG spectral mapping may potentially complement the results of ESM of language.

Quantifying Auditory Event-Related Responses in Multichannel Human Intracranial Recordings

Multichannel intracranial recordings are used increasingly to study the functional organization of human cortex. Intracranial recordings of event-related activity, or electrocorticography (ECoG), are based on high density electrode arrays implanted directly over cortex, combining good temporal and spatial resolution. Developing appropriate statistical methods for analyzing event-related responses in these high dimensional ECoG datasets remains a major challenge for clinical and systems neuroscience. We present a novel methodological framework that combines complementary, existing methods adapted for statistical analysis of auditory event-related responses in multichannel ECoG recordings. This analytic framework integrates single-channel (time-domain, time–frequency) and multichannel analyses of event-related ECoG activity to determine statistically significant evoked responses, induced spectral responses, and effective (causal) connectivity. Implementation of this quantitative approach is illustrated using multichannel ECoG data from recent studies of auditory processing in patients with epilepsy. Methods described include a time–frequency matching pursuit algorithm adapted for modeling brief, transient cortical spectral responses to sound, and a recently developed method for estimating effective connectivity using multivariate autoregressive modeling to measure brief event-related changes in multichannel functional interactions. A semi-automated spatial normalization method for comparing intracranial electrode locations across patients is also described. The individual methods presented are published and readily accessible. We discuss the benefits of integrating multiple complementary methods in a unified and comprehensive quantitative approach. Methodological considerations in the analysis of multichannel ECoG data, including corrections for multiple comparisons are discussed, as well as remaining challenges in the development of new statistical approaches.

Spatial-temporal functional mapping of language at the bedside with electrocorticography

Objective: To investigate the feasibility and clinical utility of using passive electrocorticography (ECoG) for online spatial-temporal functional mapping (STFM) of language cortex in patients being monitored for epilepsy surgery. Methods: We developed and tested an online system that exploits ECoGs temporal resolution to display the evolution of statistically significant high gamma (70–110 Hz) responses across all recording sites activated by a discrete cognitive task. We illustrate how this spatial-temporal evolution can be used to study the function of individual recording sites engaged during different language tasks, and how this approach can be particularly useful for mapping eloquent cortex. Results: Using electrocortical stimulation mapping (ESM) as the clinical gold standard for localizing language cortex, the average sensitivity and specificity of online STFM across 7 patients were 69.9% and 83.5%, respectively. Moreover, relative to regions of interest where discrete cortical lesions have most reliably caused language impairments in the literature, the sensitivity of STFM was significantly greater than that of ESM, while its specificity was also greater than that of ESM, though not significantly so. Conclusions: This study supports the feasibility and clinical utility of online STFM for mapping human language function, particularly under clinical circumstances in which time is limited and comprehensive ESM is impractical.

A Dynamic Directional Model for Effective Brain Connectivity Using Electrocorticographic (ECoG) Time Series

We introduce a dynamic directional model (DDM) for studying brain effective connectivity based on intracranial electrocorticographic (ECoG) time series. The DDM consists of two parts: a set of differential equations describing neuronal activity of brain components (state equations), and observation equations linking the underlying neuronal states to observed data. When applied to functional MRI or EEG data, DDMs usually have complex formulations and thus can accommodate only a few regions, due to limitations in spatial resolution and/or temporal resolution of these imaging modalities. In contrast, we formulate our model in the context of ECoG data. The combined high temporal and spatial resolution of ECoG data result in a much simpler DDM, allowing investigation of complex connections between many regions. To identify functionally segregated subnetworks, a form of biologically economical brain networks, we propose the Potts model for the DDM parameters. The neuronal states of brain components are represented by cubic spline bases and the parameters are estimated by minimizing a log-likelihood criterion that combines the state and observation equations. The Potts model is converted to the Potts penalty in the penalized regression approach to achieve sparsity in parameter estimation, for which a fast iterative algorithm is developed. The methods are applied to an auditory ECoG dataset.

Auditory processing following consecutive right temporal lobe resections: a prospective case study.

BACKGROUND The role of the right temporal lobe in processing speech is not well understood. Although the left temporal lobe has long been recognized as critical for speech perception, there is growing evidence for right hemisphere involvement. To investigate whether the right temporal lobe is critical for auditory speech processing, we studied prospectively a normal-hearing patient who underwent consecutive right temporal lobe resections for treatment of medically intractable seizures. PURPOSE To test the hypothesis that the right temporal lobe is critical for auditory speech processing. RESEARCH DESIGN We used a prospective, repeated-measure, single-case design. Auditory processing was evaluated using behavioral tests of speech recognition (words, sentences) under multiple listening conditions (e.g., quiet, background noise, etc.). Auditory processing of nonspeech sounds was measured by pitch pattern sequencing and environmental sound recognition tasks. DATA COLLECTION Repeat behavioral testing was performed at four time points over a 2 yr period: before and after consecutive right temporal lobe resection surgeries. RESULTS Before surgery, the patient demonstrated normal speech recognition in quiet and under real-world listening conditions (background noise, filtered speech). After the initial right anterior temporal resection, speech recognition scores declined under adverse listening conditions, especially for the left ear, but remained largely within normal limits. Following resection of the right superior temporal gyrus 1 yr later, speech recognition in quiet and nonspeech sound processing (pitch patterns, environmental sounds) remained intact. However, speech recognition under adverse listening conditions was severely impaired. CONCLUSIONS The right superior temporal gyrus appears to be critical for auditory processing of speech under real-world listening conditions.

Multi-Regional Adaptation in Human Auditory Association Cortex

In auditory cortex, neural responses decrease with stimulus repetition, known as adaptation. Adaptation is thought to facilitate detection of novel sounds and improve perception in noisy environments. Although it is well established that adaptation occurs in primary auditory cortex, it is not known whether adaptation also occurs in higher auditory areas involved in processing complex sounds, such as speech. Resolving this issue is important for understanding the neural bases of adaptation and to avoid potential post-operative deficits after temporal lobe surgery for treatment of focal epilepsy. Intracranial electrocorticographic recordings were acquired simultaneously from electrodes implanted in primary and association auditory areas of the right (non-dominant) temporal lobe in a patient with complex partial seizures originating from the inferior parietal lobe. Simple and complex sounds were presented in a passive oddball paradigm. We measured changes in single-trial high-gamma power (70–150 Hz) and in regional and inter-regional network-level activity indexed by cross-frequency coupling. Repetitive tones elicited the greatest adaptation and corresponding increases in cross-frequency coupling in primary auditory cortex. Conversely, auditory association cortex showed stronger adaptation for complex sounds, including speech. This first report of multi-regional adaptation in human auditory cortex highlights the role of the non-dominant temporal lobe in suppressing neural responses to repetitive background sounds (noise). These results underscore the clinical utility of functional mapping to avoid potential post-operative deficits including increased listening difficulties in noisy, real-world environments.

Modeling Neural Adaptation in Auditory Cortex

Neural responses recorded from auditory cortex exhibit adaptation, a stimulus-specific decrease that occurs when the same sound is presented repeatedly. Stimulus-specific adaptation is thought to facilitate perception in noisy environments. Although adaptation is assumed to arise independently from cortex, this has been difficult to validate directly in vivo. In this study, we used a neural network model of auditory cortex with multicompartmental cell modeling to investigate cortical adaptation. We found that repetitive, non-adapted inputs to layer IV neurons in the model elicited frequency-specific decreases in simulated single neuron, population-level and local field potential (LFP) activity, consistent with stimulus-specific cortical adaptation. Simulated recordings of LFPs, generated solely by excitatory post-synaptic inputs and recorded from layers II/III in the model, showed similar waveform morphologies and stimulus probability effects as auditory evoked responses recorded from human cortex. We tested two proposed mechanisms of cortical adaptation, neural fatigue and neural sharpening, by varying the strength and type of inter- and intra-layer synaptic connections (excitatory, inhibitory). Model simulations showed that synaptic depression modeled in excitatory (AMPA) synapses was sufficient to elicit a reduction in neural firing rate, consistent with neural fatigue. However, introduction of lateral inhibition from local layer II/III interneurons resulted in a reduction in the number of responding neurons, but not their firing rates, consistent with neural sharpening. These modeling results demonstrate that adaptation can arise from multiple neural mechanisms in auditory cortex.

Bayesian inference of high-dimensional, cluster-structured ordinary differential equation models with applications to brain connectivity studies

We build a new ordinary differential equation (ODE) model for the directional interaction, also called effective connectivity, among brain regions whose activities are measured by intracranial electrocorticography (ECoG) data. In contrast to existing ODE models that focus on effective connectivity among only a few large anatomic brain regions and that rely on strong prior belief of the existence and strength of the connectivity, the proposed high-dimensional ODE model, motivated by statistical considerations, can be used to explore connectivity among multiple small brain regions. The new model, called the modular and indicator-based dynamic directional model (MIDDM), features a cluster structure, which consists of modules of densely connected brain regions, and uses indicators to differentiate significant and void directional interactions among brain regions. We develop a unified Bayesian framework to quantify uncertainty in the assumed ODE model, identify clusters, select strongly connected brain regions, and make statistical comparison between brain networks across different experimental trials. The prior distributions in the Bayesian model for MIDDM parameters are carefully designed such that the ensuing joint posterior distributions for ODE state functions and the MIDDM parameters have well-defined and easy-to-simulate posterior conditional distributions. To further speed up the posterior simulation, we employ parallel computing schemes in Markov chain Monte Carlo steps. We show that the proposed Bayesian approach outperforms an existing optimization-based ODE estimation method. We apply the proposed method to an auditory electrocorticography dataset and evaluate brain auditory network changes across trials and different auditory stimuli.