Intracranial Electrophysiology Research Articles

Mapping the emergence of visual consciousness in the human brain via brain-wide intracranial electrophysiology

Consciousness lies at the heart of our existence and experience. To probe how perceptual consciousness emerges in the brain, we recorded brain-wide intracranial electroencephalography signals from human patients while their perceptual consciousness was effectively manipulated using the continuous flash suppression paradigm. We observed substantial differences in brain activities when visual information gradually enters consciousness. Specifically, the functional connectivity first increases and then decreases, oscillations in the low-frequency band reduce in power, and those in the high-frequency band remain unchanged. We employed random forest-based classification to characterize the transitions from no perception to subconsciousness and then to consciousness, which showed an increase in signal variance at the second transition rather than the first. Further, the frontal-parietal junction dominates the first transition, whereas the temporal-frontal lobes dominate the second transition. Finally, we identified the most relevant neuronal features associated with consciousness. Altogether, these findings shed fresh light on the emergence of visual consciousness.

Imaging versus electrographic connectivity in human mood-related fronto-temporal networks

BackgroundThe efficacy of psychiatric DBS is thought to be driven by the connectivity of stimulation targets with mood-relevant fronto-temporal networks, which is typically evaluated using diffusion-weighted tractography. ObjectiveLeverage intracranial electrophysiology recordings to better predict the circuit-wide effects of neuromodulation to white matter targets. We hypothesize strong convergence between tractography-predicted structural connectivity and stimulation-induced electrophysiological responses. MethodsEvoked potentials were elicited by single-pulse stimulation to two common DBS targets for treatment-resistant depression – the subcallosal cingulate (SCC) and ventral capsule/ventral striatum (VCVS) – in two patients undergoing DBS with stereo-electroencephalographic (sEEG) monitoring. Evoked potentials were compared with predicted structural connectivity between DBS leads and sEEG contacts using probabilistic, patient-specific diffusion-weighted tractography. ResultsEvoked potentials and tractography showed strong convergence in both patients in orbitofrontal, ventromedial prefrontal, and lateral prefrontal cortices for both SCC and VCVS stimulation targets. Low convergence was found in anterior cingulate (ACC), where tractography predicted structural connectivity from SCC targets but produced no evoked potentials during SCC stimulation. Further, tractography predicted no connectivity to ACC from VCVS targets, but VCVS stimulation produced robust evoked potentials. ConclusionThe two connectivity methods showed significant convergence, but important differences emerged with respect to the ability of tractography to predict electrophysiological connectivity between SCC and VCVS to regions of the mood-related network. This multimodal approach raises intriguing implications for the use of tractography in surgical targeting and provides new data to enhance our understanding of the network-wide effects of neuromodulation.

LeGUI: A Fast and Accurate Graphical User Interface for Automated Detection and Anatomical Localization of Intracranial Electrodes.

Accurate anatomical localization of intracranial electrodes is important for identifying the seizure foci in patients with epilepsy and for interpreting effects from cognitive studies employing intracranial electroencephalography. Localization is typically performed by coregistering postimplant computed tomography (CT) with preoperative magnetic resonance imaging (MRI). Electrodes are then detected in the CT, and the corresponding brain region is identified using the MRI. Many existing software packages for electrode localization chain together separate preexisting programs or rely on command line instructions to perform the various localization steps, making them difficult to install and operate for a typical user. Further, many packages provide solutions for some, but not all, of the steps needed for confident localization. We have developed software, Locate electrodes Graphical User Interface (LeGUI), that consists of a single interface to perform all steps needed to localize both surface and depth/penetrating intracranial electrodes, including coregistration of the CT to MRI, normalization of the MRI to the Montreal Neurological Institute template, automated electrode detection for multiple types of electrodes, electrode spacing correction and projection to the brain surface, electrode labeling, and anatomical targeting. The software is written in MATLAB, core image processing is performed using the Statistical Parametric Mapping toolbox, and standalone executable binaries are available for Windows, Mac, and Linux platforms. LeGUI was tested and validated on 51 datasets from two universities. The total user and computational time required to process a single dataset was approximately 1 h. Automatic electrode detection correctly identified 4362 of 4695 surface and depth electrodes with only 71 false positives. Anatomical targeting was verified by comparing electrode locations from LeGUI to locations that were assigned by an experienced neuroanatomist. LeGUI showed a 94% match with the 482 neuroanatomist-assigned locations. LeGUI combines all the features needed for fast and accurate anatomical localization of intracranial electrodes into a single interface, making it a valuable tool for intracranial electrophysiology research.

Ongoing neural oscillations influence behavior and sensory representations by suppressing neuronal excitability

The ability to process and respond to external input is critical for adaptive behavior. Why, then, do neural and behavioral responses vary across repeated presentations of the same sensory input? Ongoing fluctuations of neuronal excitability are currently hypothesized to underlie the trial-by-trial variability in sensory processing. To test this, we capitalized on intracranial electrophysiology in neurosurgical patients performing an auditory discrimination task with visual cues: specifically, we examined the interaction between prestimulus alpha oscillations, excitability, task performance, and decoded neural stimulus representations. We found that strong prestimulus oscillations in the alpha+ band (i.e., alpha and neighboring frequencies), rather than the aperiodic signal, correlated with a low excitability state, indexed by reduced broadband high-frequency activity. This state was related to slower reaction times and reduced neural stimulus encoding strength. We propose that the alpha+ rhythm modulates excitability, thereby resulting in variability in behavior and sensory representations despite identical input.

Long-term ecological assessment of intracranial electrophysiology synchronized to behavioral markers in obsessive-compulsive disorder.

Detection of neural signatures related to pathological behavioral states could enable adaptive deep brain stimulation (DBS), a potential strategy for improving efficacy of DBS for neurological and psychiatric disorders. This approach requires identifying neural biomarkers of relevant behavioral states, a task best performed in ecologically valid environments. Here, in human participants with obsessive-compulsive disorder (OCD) implanted with recording-capable DBS devices, we synchronized chronic ventral striatum local field potentials with relevant, disease-specific behaviors. We captured over 1,000 h of local field potentials in the clinic and at home during unstructured activity, as well as during DBS and exposure therapy. The wide range of symptom severity over which the data were captured allowed us to identify candidate neural biomarkers of OCD symptom intensity. This work demonstrates the feasibility and utility of capturing chronic intracranial electrophysiology during daily symptom fluctuations to enable neural biomarker identification, a prerequisite for future development of adaptive DBS for OCD and other psychiatric disorders.

An Intracranial Electrophysiology Study of Visual Language Encoding: The Contribution of the Precentral Gyrus to Silent Reading.

Models of reading emphasize that visual (orthographic) processing provides input to phonological as well as lexical-semantic processing. Neurobiological models of reading have mapped these processes to distributed regions across occipital-temporal, temporal-parietal, and frontal cortices. However, the role of the precentral gyrus in these models is ambiguous. Articulatory phonemic representations in the precentral gyrus are obviously involved in reading aloud, but it is unclear if the precentral gyrus is recruited during reading silently in a time window consistent with participation in phonological processing contributions. Here, we recorded intracranial electrophysiology during a speeded semantic decision task from 24 patients to map the spatio-temporal flow of information across the cortex during silent reading. Patients selected animate nouns from a stream of nonanimate words, letter strings, and false-font stimuli. We characterized the distribution and timing of evoked high-gamma power (70-170 Hz) as well as phase-locking between electrodes. The precentral gyrus showed a proportion of electrodes responsive to linguistic stimuli (27%) that was at least as high as those of surrounding peri-sylvian regions. These precentral gyrus electrodes had significantly greater high-gamma power for words compared to both false-font and letter-string stimuli. In a patient with word-selective effects in the fusiform, superior temporal, and precentral gyri, there was significant phase-locking between the fusiform and precentral gyri starting at ∼180 msec and between the precentral and superior temporal gyri starting at ∼220 msec. Finally, our large patient cohort allowed exploratory analyses of the spatio-temporal reading network underlying silent reading. The distribution, timing, and connectivity results place the precentral gyrus as an important hub in the silent reading network.

FMRI and intra-cranial electrocorticography recordings in the same human subjects reveals negative BOLD signal coupled with silenced neuronal activity

Positive blood oxygenation level-dependent (BOLD) responses (PBR), as measured by functional Magnetic Resonance Imaging (fMRI), are the most utilized measurements to non-invasively map activity in the brain. Recent studies have consistently shown that BOLD responses are not exclusively positive. Negative BOLD responses (NBR) have been reported in response to specific sensory stimulations and tasks. However, the exact relationship between NBR and the underlying metabolic and neuronal demand is still under debate. In this study, we investigated the neurophysiological basis of negative BOLD using fMRI and intra-cranial electrophysiology (electrocorticography, ECoG) measurements from the same human participants. We show that, for those electrodes that responded to visual stimulation, PBR are correlated with high-frequency band (HFB) responses. Crucially, NBR were associated with an absence of HFB power responses and an unpredicted decrease in the alpha power responses.

Ethical Issues in Intraoperative Neuroscience Research: Assessing Subjects’ Recall of Informed Consent and Motivations for Participation

Background An increasing number of studies utilize intracranial electrophysiology in human subjects to advance basic neuroscience knowledge. However, the use of neurosurgical patients as human research subjects raises important ethical considerations, particularly regarding informed consent and undue influence, as well as subjects’ motivations for participation. Yet a thorough empirical examination of these issues in a participant population has been lacking. The present study therefore aimed to empirically investigate ethical concerns regarding informed consent and voluntariness in Parkinson’s disease patients undergoing deep brain stimulator (DBS) placement who participated in an intraoperative neuroscience study. Methods Two semi-structured 30-minute interviews were conducted preoperatively and postoperatively via telephone. Interviews assessed participants’ motivations for participation in the parent intraoperative study, recall of information presented during the informed consent process, and participants’ postoperative reflections on the research study. Results Twenty-two participants (mean age = 60.9) completed preoperative interviews at a mean of 7.8 days following informed consent and a mean of 5.2 days prior to DBS surgery. Twenty participants completed postoperative interviews at a mean of 5 weeks following surgery. All participants cited altruism or advancing medical science as “very important” or “important” in their decision to participate in the study. Only 22.7% (n = 5) correctly recalled one of the two risks of the study. Correct recall of other aspects of the informed consent was poor (36.4% for study purpose; 50.0% for study protocol; 36.4% for study benefits). All correctly understood that the study would not confer a direct therapeutic benefit to them. Conclusion Even though research coordinators were properly trained and the informed consent was administered according to protocol, participants demonstrated poor retention of study information. While intraoperative studies that aim to advance neuroscience knowledge represent a unique opportunity to gain fundamental scientific knowledge, improved standards for the informed consent process can help facilitate their ethical implementation.

Cortical Responses to Vowel Sequences in Awake and Anesthetized States: A Human Intracranial Electrophysiology Study.

Elucidating neural signatures of sensory processing across consciousness states is a major focus in neuroscience. Noninvasive human studies using the general anesthetic propofol reveal differential effects on auditory cortical activity, with a greater impact on nonprimary and auditory-related areas than primary auditory cortex. This study used intracranial electroencephalography to examine cortical responses to vowel sequences during induction of general anesthesia with propofol. Subjects were adult neurosurgical patients with intracranial electrodes placed to identify epileptic foci. Data were collected before electrode removal surgery. Stimuli were vowel sequences presented in a target detection task during awake, sedated, and unresponsive states. Averaged evoked potentials (AEPs) and high gamma (70-150Hz) power were measured in auditory, auditory-related, and prefrontal cortex. In the awake state, AEPs were found throughout studied brain areas; high gamma activity was limited to canonical auditory cortex. Sedation led to a decrease in AEP magnitude. Upon LOC, there was a decrease in the superior temporal gyrus and adjacent auditory-related cortex and a further decrease in AEP magnitude in core auditory cortex, changes in the temporal structure and increased trial-to-trial variability of responses. The findings identify putative biomarkers of LOC and serve as a foundation for future investigations of altered sensory processing.

Promises and pitfalls of topological data analysis for brain connectivity analysis

Developing sensitive and reliable methods to distinguish normal and abnormal brain states is a key neuroscientific challenge. Topological Data Analysis, despite its relative novelty, already generated many promising applications, including in neuroscience. We conjecture its prominent tool of persistent homology may benefit from going beyond analysing structural and functional connectivity to effective connectivity graphs capturing the direct causal interactions or information flows. Therefore, we assess the potential of persistent homology to directed brain network analysis by testing its discriminatory power in two distinctive examples of disease-related brain connectivity alterations: epilepsy and schizophrenia. We estimate connectivity from functional magnetic resonance imaging and electrophysiology data, employ Persistent Homology and quantify its ability to distinguish healthy from diseased brain states by applying a support vector machine to features quantifying persistent homology structure.We show how this novel approach compares to classification using standard undirected approaches and original connectivity matrices. In the schizophrenia classification, topological data analysis generally performs close to random, while classifications from raw connectivity perform substantially better; potentially due to topographical, rather than topological, specificity of the differences. In the easier task of seizure discrimination from scalp electroencephalography data, classification based on persistent homology features generally reached comparable performance to using raw connectivity, albeit with typically smaller accuracies obtained for the directed (effective) connectivity compared to the undirected (functional) connectivity. Specific applications for topological data analysis may open when direct comparison of connectivity matrices is unsuitable - such as for intracranial electrophysiology with individual number and location of measurements. While standard homology performed overall better than directed homology, this could be due to notorious technical problems of accurate effective connectivity estimation.

Highlights From AES2020, a Virtual American Epilepsy Society Experience.

Due to COVID-19 a live, in-person meeting was not possible for the American Epilepsy Society in 2020. An alternative, virtual event, the AES2020, was held instead. AES2020 was a great success with 4679 attendees from 70 countries. The educational content was outstanding and spanned the causes, treatments, and outcomes from epileptic encephalopathy to the iatrogenicity of epilepsy interventions to neurocognitive disabilities to the approach to neocortical epilepsies. New gene therapy approaches such as antisense oligonucleotide treatment for Dravet syndrome were introduced and neuromodulation devices were discussed. There were many other topics discussed in special interest groups and investigators’ workshops. A highlight was having a Nobel prize winner speak about memory processing. Human intracranial electrophysiology contributes insights into memory processing and complements animal work. In a special COVID symposium, the impact of COVID on patients with epilepsy was reviewed. Telehealth has been expanded rapidly and may be well suited for some parts of epilepsy care. In summary, the epilepsy community was alive and engaged despite being limited to a virtual platform.

Stereoelectroencephalography-guided radiofrequency thermocoagulation for hypothalamic hamartoma: Electroclinical patterns and the relationship with surgical prognosis

BackgroundRadiofrequency thermocoagulation (RFTC) guided by stereo-electroencephalography (SEEG) has been proved to be a safe method to reduce seizure frequency in patients with drug-resistant epilepsy. However, there are few reports addressing the value and safety of this procedure in hypothalamic hamartoma (HH). ObjectiveTo present the results of our experience using SEEG-guided RFTC in HH patients with drug-resistant epilepsy, and identify outcome predictors. MethodsWe retrospectively reviewed the clinical and surgical characteristics of 27 HH-related patients with epilepsy in our center between 2015 and 2019. All patients underwent invasive recordings with SEEG before RFTC was performed. We reported surgical outcome predictors and postoperative follow-up concerning safety and efficacy (mean follow-up, 27.3 months; range, 12–63). Surgical strategy was also analyzed. ResultsNineteen patients (70.4%) achieved Engel’s class I outcome, while 4 patients (14.8%) did not show significant improvement. Of all observed seizures, two different onset patterns of intracranial electrophysiology recorded by SEEG were observed. Patients presented with focal low-voltage fast activity were more likely to obtain seizure freedom (p = 0.045), while classification (p = 0.478), volume (p = 0.546), history of resection (p = 0.713), seizure types (p = 0.859), or seizure duration (p = 0.415) showed no significant effect on the outcome. Weight gain was the most common long-term complication (18.5%). ConclusionThe SEEG can guide the ablation of HH and serve as an important factor to predict favorable seizure outcomes. Radiofrequency thermocoagulation guided by SEEG can offer a minimally invasive and low-risk surgical approach with excellent outcomes. Disconnecting the attachment of HH should be the appropriate strategy to obtain the best seizure outcome.

Human hippocampal connectivity is stronger in olfaction than other sensory systems.

During mammalian evolution, primate neocortex expanded, shifting hippocampal functional networks away from primary sensory cortices, towards association cortices. Reflecting this rerouting, human resting hippocampal functional networks preferentially include higher association cortices, while those in rodents retained primary sensory cortices. Research on human visual, auditory and somatosensory systems shows evidence of this rerouting. Olfaction, however, is unique among sensory systems in its relative structural conservation throughout mammalian evolution, and it is unknown whether human primary olfactory cortex was subject to the same rerouting. We combined functional neuroimaging and intracranial electrophysiology to directly compare hippocampal functional networks across human sensory systems. We show that human primary olfactory cortex-including the anterior olfactory nucleus, olfactory tubercle and piriform cortex-has stronger functional connectivity with hippocampal networks at rest, compared to other sensory systems. This suggests that unlike other sensory systems, olfactory-hippocampal connectivity may have been retained in mammalian evolution. We further show that olfactory-hippocampal connectivity oscillates with nasal breathing. Our findings suggest olfaction might provide insight into how memory and cognition depend on hippocampal interactions.

Neurovascular networks in epilepsy: Correlating ictal blood perfusion with intracranial electrophysiology

Perfusion patterns observed in Subtraction Ictal SPECT Co-registered to MRI (SISCOM) assist in focus localization and surgical planning for patients with medically intractable focal epilepsy. While the localizing value of SISCOM has been widely investigated, its relationship to the underlying electrophysiology has not been extensively studied and is therefore not well understood. In the present study, we set to investigate this relationship in a cohort of 70 consecutive patients who underwent ictal and interictal SPECT studies and subsequent stereo-electroencephalography (SEEG) monitoring for localization of the epileptogenic focus and surgical intervention. Seizures recorded during SEEG evaluation (SEEG seizures) were matched to semiologically-similar seizures during the preoperative ictal SPECT evaluation (SPECT seizures) by comparing the semiological changes in the course of each seizure. The spectral changes of the ictal SEEG with respect to interictal ones over 7 traditional frequency bands (0.1 to 150Hz) were analyzed at each SEEG site. Neurovascular (SEEG/SPECT) relations were assessed by comparing the estimated spectral power density changes of the SEEG at each site with the perfusion changes (SISCOM z-scores) estimated from the acquired SISCOM map at that site. Across patients, a significant correlation (p<0.05) was observed between spectral changes during the SEEG seizure and SISCOM perfusion z-scores. Brain sites with high perfusion z-score exhibited higher increased SEEG power in theta to ripple frequency bands with concurrent suppression in delta and theta frequency bands compared to regions with lower perfusion z-score. The dynamics of the correlation of SISCOM perfusion and SEEG spectral power from ictal onset to seizure end and immediate postictal period were also derived. Forty-six (46) of the 70 patients underwent resective epilepsy surgery. SISCOM z-score and power increase in beta to ripple frequency bands were significantly higher in resected than non-resected sites in the patients who were seizure-free following surgery. This study provides for the first time concrete evidence that both hyper-perfusion and hypo-perfusion patterns observed in SISCOM maps have strong electrophysiological underpinnings, and that integration of the information from SISCOM and SEEG can shed light on the location and dynamics of the underlying epileptic brain networks, and thus advance our anatomo-electro-clinical understanding and approaches to targeted diagnostic and therapeutic interventions.

A Qualitative Analysis of Ethical Perspectives on Recruitment and Consent for Human Intracranial Electrophysiology Studies

Intracranial electrophysiological research methods, including those applying electrodes on the cortical surface or in deep structures, have become increasingly important in human neuroscience. They also pose novel ethical concerns, as human studies require the participation of neurological patients undergoing surgery for conditions such as epilepsy and Parkinson’s disease. Research participants in this setting may be vulnerable to conflicts of interest, therapeutic misconception, and other threats to valid recruitment and consent. We conducted semi-structured interviews with investigators from NIH-funded studies involving recording or stimulation inside the human skull. We elicited perspectives on study recruitment and consent procedures, and analyzed transcripts using a modified grounded theory approach. We interviewed 26 investigators from 19 separate intracranial electrophysiology studies, who described two study types: opportunity studies (n = 15) and experimental trials (n = 4). Respondents described significant heterogeneity in recruitment and consent procedures, even among studies employing similar techniques. In some studies, clinician-investigators were specifically barred from obtaining consent, while in other studies clinician-investigators were specifically required to obtain consent; regulatory guidance was inconsistent. Respondents also described various models for subject selection, the timing of consent, and continuing consent for temporally extended studies. Respondents expressed ethical concerns about participants’ vulnerability and the communication of research-related risks. We found a lack of consensus among investigators regarding recruitment and consent methods in human intracranial electrophysiology. This likely reflects the novelty and complexity of such studies and indicates a need for further discussion and development of best practices in this research domain.

Impact of Brain Surface Boundary Conditions on Electrophysiology and Implications for Electrocorticography.

Volume conduction of electrical potentials in the brain is highly influenced by the material properties and geometry of the tissue and recording devices implanted into the tissue. These effects are very large in EEG due to the volume conduction through the skull and scalp but are often neglected in intracranial electrophysiology. When considering penetrating electrodes deep in the brain, the assumption of an infinite and homogenous medium can be used when the sources are far enough from the brain surface and the electrodes to minimize the boundary effect. When the electrodes are recording from the brain's surface the effect of the boundary cannot be neglected, and the large surface area and commonly used insulating materials in surface electrode arrays may further increase the effect by altering the nature of the boundary in the immediate vicinity of the electrodes. This gives the experimenter some control over the spatial profiles of the potentials by appropriate design of the electrode arrays. We construct a simple three-layer model to describe the effect of material properties and geometry above the brain surface on the electric potentials and conduct empirical experiments to validate this model. A laminar electrode array is used to measure the effect of insulating and relatively conducting layers above the cortical surface by recording evoked potentials alternating between a dried surface and saline covering layer, respectively. Empirically, we find that an insulating boundary amplifies the potentials relative to conductive saline by about a factor of 4, and that the effect is not constrained to potentials that originate near the surface. The model is applied to predict the influence of array design and implantation procedure on the recording amplitude and spatial selectivity of the surface electrode arrays.

Spatiotemporal Integrity and Spontaneous Nonlinear Dynamic Properties of the Salience Network Revealed by Human Intracranial Electrophysiology: A Multicohort Replication.

The salience network (SN) plays a critical role in cognitive control and adaptive human behaviors, but its electrophysiological foundations and millisecond timescale dynamic temporal properties are poorly understood. Here, we use invasive intracranial EEG (iEEG) from multiple cohorts to investigate the neurophysiological underpinnings of the SN and identify dynamic temporal properties that distinguish it from the default mode network (DMN) and dorsolateral frontal-parietal network (FPN), two other large-scale brain networks that play important roles in human cognition. iEEG analysis of network interactions revealed that the anterior insula and anterior cingulate cortex, which together anchor the SN, had stronger intranetwork interactions with each other than cross-network interactions with the DMN and FPN. Analysis of directionality of information flow between the SN, DMN, and FPN revealed causal outflow hubs in the SN consistent with its role in fast temporal switching of network interactions. Analysis of regional iEEG temporal fluctuations revealed faster temporal dynamics and higher entropy of neural activity within the SN, compared to the DMN and FPN. Critically, these results were replicated across multiple cohorts. Our findings provide new insights into the neurophysiological basis of the SN, and more broadly, foundational mechanisms underlying the large-scale functional organization of the human brain.

Cortical responses to auditory novelty across task conditions: An intracranial electrophysiology study

Elucidating changes in sensory processing across attentional and arousal states is a major focus in neuroscience. The local/global deviant (LGD) stimulus paradigm engages auditory predictive coding over short (local deviance, LD) and long (global deviance, GD) time scales, and has been used to assay disruption of auditory predictive coding upon loss of consciousness. Our previous work (Nourski et al., 2018, J Neurosci 38:8441–52) examined effects of general anesthesia on short- and long-term novelty detection. GD effects were suppressed at subhypnotic doses of propofol, suggesting that they may be more related to task engagement than consciousness per se. The present study addressed this hypothesis by comparing cortical responses to auditory novelty during passive versus active listening conditions in awake listeners. Subjects were seven adult neurosurgical patients undergoing chronic invasive monitoring for medically intractable epilepsy. LGD stimuli were sequences of four identical vowels followed by a fifth identical or different vowel. In the passive condition, the stimuli were presented to subjects as they watched a silent TV program and were instructed to attend to its content. In the active condition, stimuli were presented in the absence of a TV program, and subjects were instructed to press a button in response to GD target stimuli. Intracranial recordings were made from multiple brain regions, including core and non-core auditory, auditory-related, prefrontal and sensorimotor cortex. Metrics of task performance included hit rate, sensitivity index, and reaction times. Cortical activity was measured as averaged auditory evoked potentials (AEPs) and event-related band power in high gamma (70–150 Hz) and alpha (8–14 Hz) frequency bands. The vowel stimuli and LD elicited robust AEPs in all studied brain areas in both passive and active conditions. High gamma responses to stimulus onset and LD were localized predominantly to the auditory cortex in the superior temporal plane and had a comparable prevalence and spatial extent between the two conditions. In contrast, GD effects (AEPs, high gamma and alpha suppression) were greatly enhanced during the active condition in all studied brain areas. The prevalence of high gamma GD effects was positively correlated with individual subjects’ task performance. The data demonstrate distinct task engagement-related effects on responses to auditory novelty across the auditory cortical processing hierarchy. The results motivate a closer examination of effective connectivity underlying attentional modulation of cortical sensory responses, and serve as a foundation for examining changes in sensory processing associated with general anesthesia, sleep and disorders of consciousness.

Intrinsic connectome organization across temporal scales: New insights from cross-modal approaches.

The discovery of a stable, whole-brain functional connectivity organization that is largely independent of external events has drastically extended our view of human brain function. However, this discovery has been primarily based on functional magnetic resonance imaging (fMRI). The role of this whole-brain organization in fast oscillation-based connectivity as measured, for example, by electroencephalography (EEG) and magnetoencephalography (MEG) is only beginning to emerge. Here, we review studies of intrinsic connectivity and its whole-brain organization in EEG, MEG, and intracranial electrophysiology with a particular focus on direct comparisons to connectome studies in fMRI. Synthesizing this literature, we conclude that irrespective of temporal scale over four orders of magnitude, intrinsic neurophysiological connectivity shows spatial similarity to the connectivity organization commonly observed in fMRI. A shared structural connectivity basis and cross-frequency coupling are possible mechanisms contributing to this similarity. Acknowledging that a stable whole-brain organization governs long-range coupling across all timescales of neural processing motivates researchers to take “baseline” intrinsic connectivity into account when investigating brain-behavior associations, and further encourages more widespread exploration of functional connectomics approaches beyond fMRI by using EEG and MEG modalities.

Internal noise in contrast discrimination propagates forwards from early visual cortex

Human contrast discrimination performance is limited by transduction nonlinearities and variability of the neural representation (noise). Whereas the nonlinearities have been well-characterised, there is less agreement about the specifics of internal noise. Psychophysical models assume that it impacts late in sensory processing, whereas neuroimaging and intracranial electrophysiology studies suggest that the noise is much earlier. We investigated whether perceptually-relevant internal noise arises in early visual areas or later decision making areas. We recorded EEG and MEG during a two-interval-forced-choice contrast discrimination task and used multivariate pattern analysis to decode target/non-target and selected/non-selected intervals from evoked responses. We found that perceptual decisions could be decoded from both EEG and MEG signals, even when the stimuli in both intervals were physically identical. Above-chance decision classification started <100 ms after stimulus onset, suggesting that neural noise affects sensory signals early in the visual pathway. Classification accuracy increased over time, peaking at >500 ms. Applying multivariate analysis to separate anatomically-defined brain regions in MEG source space, we found that occipital regions were informative early on but then information spreads forwards across parietal and frontal regions. This is consistent with neural noise affecting sensory processing at multiple stages of perceptual decision making. We suggest how early sensory noise might be resolved with Birdsall's linearisation, in which a dominant noise source obscures subsequent nonlinearities, to allow the visual system to preserve the wide dynamic range of early areas whilst still benefitting from contrast-invariance at later stages. A preprint of this work is available at: https://doi.org/10.1101/364612.