Use of functional magnetic resonance imaging to assess cognition and consciousness in severe Guillain-Barré syndrome.

Objective: Functional neuroimaging may provide a viable means of assessment and communication in patients with Guillain-Barré Syndrome (GBS) mimicking the complete locked-in state. Functional neuroimaging has been used to assess residual cognitive function and has allowed for binary communication with other behaviourally non-responsive patients, such as those diagnosed with unresponsive wakefulness syndrome. We evaluated the potential application of functional neuroimaging using a clinical-grade scanner to determine if individuals with severe GBS retained auditory function, command following, and communication. Methods: Fourteen healthy participants and two GBS patients were asked to perform motor imagery and spatial navigation imagery tasks while being scanned using functional magnetic resonance imaging. The GBS patients were also asked to perform additional functional neuroimaging scans to attempt communication. Results: The motor imagery and spatial navigation task elicited significant activation in appropriate regions of interest for both GBS patients, indicating intact command following. Both patients were able to use the imagery technique to communicate in some instances. Patient 1 was able to use one of four communication tasks to answer a question correctly. Patient 2 was able to use three of seven communication tasks. However, two questions were incorrectly answered while a third was non-verifiable. Conclusions: GBS patients can respond using mental imagery and these responses can be detected using functional neuroimaging. Furthermore, these patients may also be able to use mental imagery to provide answers to 'yes' or 'no' questions in some instances. We argue that the most appropriate use of neuroimaging-based communication in these patients is to allow them to communicate wishes or preferences and assent to previously expressed decisions, rather than to facilitate decision-making.

While you were sleeping: Evidence for high-level executive processing of an auditory narrative during sleep.

During sleep we lack conscious awareness of the external environment. Yet, our internal mental state suggests that high-level cognitive processes persist. The nature and extent to which the external environment is processed during sleep remain largely unexplored. Here, we used an fMRI synchronization-based approach to examine responses to a narrative during wakefulness and sleep. The stimulus elicited the auditory network and a frontoparietal pattern of activity, consistent with high-level narrative plot-following. During REM sleep, the same frontoparietal pattern was observed in one of three participants, and partially in one other, confirming that it is possible to track and follow the moment-to-moment complexities of a narrative during REM sleep. Auditory network recruitment was observed in both non-REM and REM sleep, demonstrating preservation of low-level auditory processing, even in deep sleep. This novel approach investigating cognitive processing at different levels of awareness demonstrates that the brain can meaningfully process the external environment during REM sleep.

Mapping Specific Mental Content during Musical Imagery.

Humans can mentally represent auditory information without an external stimulus, but the specificity of these internal representations remains unclear. Here, we asked how similar the temporally unfolding neural representations of imagined music are compared to those during the original perceived experience. We also tested whether rhythmic motion can influence the neural representation of music during imagery as during perception. Participants first memorized six 1-min-long instrumental musical pieces with high accuracy. Functional MRI data were collected during: 1) silent imagery of melodies to the beat of a visual metronome; 2) same but while tapping to the beat; and 3) passive listening. During imagery, inter-subject correlation analysis showed that melody-specific temporal response patterns were reinstated in right associative auditory cortices. When tapping accompanied imagery, the melody-specific neural patterns were reinstated in more extensive temporal-lobe regions bilaterally. These results indicate that the specific contents of conscious experience are encoded similarly during imagery and perception in the dynamic activity of auditory cortices. Furthermore, rhythmic motion can enhance the reinstatement of neural patterns associated with the experience of complex sounds, in keeping with models of motor to sensory influences in auditory processing.

Assessing Time-Resolved fNIRS for Brain-Computer Interface Applications of Mental Communication.

Brain-computer interfaces (BCIs) are becoming increasingly popular as a tool to improve the quality of life of patients with disabilities. Recently, time-resolved functional near-infrared spectroscopy (TR-fNIRS) based BCIs are gaining traction because of their enhanced depth sensitivity leading to lower signal contamination from the extracerebral layers. This study presents the first account of TR-fNIRS based BCI for "mental communication" on healthy participants. Twenty-one (21) participants were recruited and were repeatedly asked a series of questions where they were instructed to imagine playing tennis for "yes" and to stay relaxed for "no." The change in the mean time-of-flight of photons was used to calculate the change in concentrations of oxy- and deoxyhemoglobin since it provides a good compromise between depth sensitivity and signal-to-noise ratio. Features were extracted from the average oxyhemoglobin signals to classify them as "yes" or "no" responses. Linear-discriminant analysis (LDA) and support vector machine (SVM) classifiers were used to classify the responses using the leave-one-out cross-validation method. The overall accuracies achieved for all participants were 75% and 76%, using LDA and SVM, respectively. The results also reveal that there is no significant difference in accuracy between questions. In addition, physiological parameters [heart rate (HR) and mean arterial pressure (MAP)] were recorded on seven of the 21 participants during motor imagery (MI) and rest to investigate changes in these parameters between conditions. No significant difference in these parameters was found between conditions. These findings suggest that TR-fNIRS could be suitable as a BCI for patients with brain injuries.

Using fMRI to investigate the potential cause of inverse oxygenation reported in fNIRS studies of motor imagery.

Motor imagery (MI) is a commonly used cognitive task in brain-computer interface (BCI) applications because it produces reliable activity in motor-planning regions. However, a number of functional near-infrared spectroscopy (fNIRS) studies have reported the unexpected finding of inverse oxygenation: increased deoxyhemoglobin and decreased oxyhemoglobin during task periods. This finding questions the reliability of fNIRS for BCI applications given that MI activation should result in a focal increase in blood oxygenation. In an attempt to elucidate this phenomenon, fMRI and fNIRS data were acquired on 15 healthy participants performing a MI task. The fMRI data provided global coverage of brain activity, thus allowing visualization of all potential brain regions activated and deactivated during task periods. Indeed, fMRI results from seven subjects included activation in the primary motor cortex and/or the pre-supplementary motor area during the rest periods in addition to the expected activation in the supplementary motor and premotor areas. Of these seven subjects, two showed inverse oxygenation with fNIRS. The proximity of the regions showing inverse oxygenation to the motor planning regions suggests that inverse activation detected by fNIRS may likely be a consequence of partial volume errors due to the sensitivity of the optodes to both primary motor and motor planning regions.

The neural basis of external responsiveness in prolonged disorders of consciousness.

OBJECTIVE: To investigate the structural integrity of fibre tracts underlying overt motor behaviour in PDOC. METHODS: This cross-sectional study examined 15 PDOC patients and 22 healthy participants. Eight PDOC patients met the criteria for the vegetative state, 5 met the criteria for the minimally conscious state and 2 met the criteria for emerging from the minimally conscious state. We used fibre tractography to reconstruct the white matter fibres known to be involved in voluntary motor execution (i.e., those connecting thalamus with M1, M1 with cerebellum, and cerebellum with thalamus) and used fractional anisotropy (FA) as a measure of their integrity. RESULTS: PDOC patients showed significantly reduced FA relative to controls on the fibres connecting thalamus and M1. This went above and beyond a widespread injury to the white matter and correlated with clinical severity. In a subset of patients, we also identified a similar pattern of injury in the fibres connecting M1 and cerebellum but a relative preservation of those connecting cerebellum and thalamus. CONCLUSIONS: Our results suggest that structural damage to motor fibres may lead to reduced responsiveness in PDOC patients across all diagnostic sub-categories, and therefore behavioural assessments may underestimate the level of retained cognitive function and awareness across the PDOC spectrum.

Disentangling disorders of consciousness: Insights from diffusion tensor imaging and machine learning.

Previous studies have suggested that disorders of consciousness (DOC) after severe brain injury may result from disconnections of the thalamo-cortical system. However, thalamo-cortical connectivity differences between vegetative state (VS), minimally conscious state minus (MCS-, i.e., low-level behavior such as visual pursuit), and minimally conscious state plus (MCS+, i.e., high-level behavior such as language processing) remain unclear. Probabilistic tractography in a sample of 25 DOC patients was employed to assess whether structural connectivity in various thalamo-cortical circuits could differentiate between VS, MCS-, and MCS+ patients. First, the thalamus was individually segmented into seven clusters based on patterns of cortical connectivity and tested for univariate differences across groups. Second, reconstructed whole-brain thalamic tracks were used as features in a multivariate searchlight analysis to identify regions along the tracks that were most informative in distinguishing among groups. At the univariate level, it was found that VS patients displayed reduced connectivity in most thalamo-cortical circuits of interest, including frontal, temporal, and sensorimotor connections, as compared with MCS+, but showed more pulvinar-occipital connections when compared with MCS-. Moreover, MCS- exhibited significantly less thalamo-premotor and thalamo-temporal connectivity than MCS+. At the multivariate level, it was found that thalamic tracks reaching frontal, parietal, and sensorimotor regions, could discriminate, up to 100% accuracy, across each pairwise group comparison. Together, these findings highlight the role of thalamo-cortical connections in patients' behavioral profile and level of consciousness. Diffusion tensor imaging combined with machine learning algorithms could thus potentially facilitate diagnostic distinctions in DOC and shed light on the neural correlates of consciousness. Hum Brain Mapp 38:431-443, 2017. © 2016 Wiley Periodicals, Inc.

A hierarchy of event-related potential markers of auditory processing in disorders of consciousness.

Functional neuroimaging of covert perceptual and cognitive processes can inform the diagnoses and prognoses of patients with disorders of consciousness, such as the vegetative and minimally conscious states (VS;MCS). Here we report an event-related potential (ERP) paradigm for detecting a hierarchy of auditory processes in a group of healthy individuals and patients with disorders of consciousness. Simple cortical responses to sounds were observed in all 16 patients; 7/16 (44%) patients exhibited markers of the differential processing of speech and noise; and 1 patient produced evidence of the semantic processing of speech (i.e. the N400 effect). In several patients, the level of auditory processing that was evident from ERPs was higher than the abilities that were evident from behavioural assessment, indicating a greater sensitivity of ERPs in some cases. However, there were no differences in auditory processing between VS and MCS patient groups, indicating a lack of diagnostic specificity for this paradigm. Reliably detecting semantic processing by means of the N400 effect in passively listening single-subjects is a challenge. Multiple assessment methods are needed in order to fully characterise the abilities of patients with disorders of consciousness.

Relationship between the anterior forebrain mesocircuit and the default mode network in the structural bases of disorders of consciousness.

The specific neural bases of disorders of consciousness (DOC) are still not well understood. Some studies have suggested that functional and structural impairments in the default mode network may play a role in explaining these disorders. In contrast, others have proposed that dysfunctions in the anterior forebrain mesocircuit involving striatum, globus pallidus, and thalamus may be the main underlying mechanism. Here, we provide the first report of structural integrity of fiber tracts connecting the nodes of the mesocircuit and the default mode network in 8 patients with DOC. We found evidence of significant damage to subcortico-cortical and cortico-cortical fibers, which were more severe in vegetative state patients and correlated with clinical severity as determined by Coma Recovery Scale-Revised (CRS-R) scores. In contrast, fiber tracts interconnecting subcortical nodes were not significantly impaired. Lastly, we found significant damage in all fiber tracts connecting the precuneus with cortical and subcortical areas. Our results suggest a strong relationship between the default mode network - and most importantly the precuneus - and the anterior forebrain mesocircuit in the neural basis of the DOC.

A Thalamocortical Mechanism for the Absence of Overt Motor Behavior in Covertly Aware Patients.

IMPORTANCE: It is well accepted that a significant number of patients in a vegetative state are covertly aware and capable of following commands by modulating their neural responses in motor imagery tasks despite remaining nonresponsive behaviorally. To date, there have been few attempts to explain this dissociation between preserved covert motor behavior and absent overt motor behavior. OBJECTIVES: To investigate the differential neural substrates of overt and covert motor behavior and assess the structural integrity of the underlying networks in behaviorally nonresponsive patients. DESIGN, SETTING, AND PARTICIPANTS: A case-control study was conducted at an academic center between February 7, 2012, and November 6, 2014. Data analysis was performed between March 2014 and June 2015. Participants included a convenience sample of 2 patients with severe brain injury: a paradigmatic patient who fulfilled all clinical criteria for the vegetative state but produced repeated evidence of covert awareness (patient 1) and, as a control case, a patient with similar clinical variables but capable of behavioral command following (patient 2). Fifteen volunteers participated in the study as a healthy control group. MAIN OUTCOMES AND MEASURES: We used dynamic causal modeling of functional magnetic resonance imaging to compare voluntary motor imagery and motor execution. We then used fiber tractography to assess the structural integrity of the fibers that our functional magnetic resonance imaging study revealed as essential for successful motor execution. RESULTS: The functional magnetic resonance imaging study revealed that, in contrast to mental imagery, motor execution was associated with an excitatory coupling between the thalamus and primary motor cortex (Bayesian model selection; winning model Bayes factors >17). Moreover, we detected a selective structural disruption in the fibers connecting these 2 regions in patient 1 (fractional anisotropy, 0.294; P = .047) but not in patient 2 (fractional anisotropy, 0.413; P = .35). CONCLUSIONS AND RELEVANCE: These results suggest a possible biomarker for the absence of intentional movement in covertly aware patients (ie, specific damage to motor thalamocortical fibers), highlight the importance of the thalamus for the execution of intentional movements, and may provide a target for restorative therapies in behaviorally nonresponsive patients.

Thalamic and extrathalamic mechanisms of consciousness after severe brain injury.

OBJECTIVE: What mechanisms underlie the loss and recovery of consciousness after severe brain injury? We sought to establish, in the largest cohort of patients with disorders of consciousness (DOC) to date, the link between gold standard clinical measures of awareness and wakefulness, and specific patterns of local brain pathology-thereby possibly providing a mechanistic framework for patient diagnosis, prognosis, and treatment development. METHODS: Structural T1-weighted magnetic resonance images were collected, in a continuous sample of 143 severely brain-injured patients with DOC (and 96 volunteers), across 2 tertiary expert centers. Brain atrophy in subcortical regions (bilateral thalamus, basal ganglia, hippocampus, basal forebrain, and brainstem) was assessed across (1) healthy volunteers and patients, (2) clinical entities (eg, vegetative state, minimally conscious state), (3) clinical measures of consciousness (Coma Recovery Scale-Revised), and (4) injury etiology. RESULTS: Compared to volunteers, patients exhibited significant atrophy across all structures (p < 0.05, corrected). Strikingly, we found almost no significant differences across clinical entities. Nonetheless, the clinical measures of awareness and wakefulness upon which differential diagnosis rely were systematically associated with tissue atrophy within thalamic and basal ganglia nuclei, respectively; the basal forebrain was atrophied in proportion to patients' response to sensory stimulation. In addition, nontraumatic injuries exhibited more extensive thalamic atrophy. INTERPRETATION: These findings provide, for the first time, a grounding in pathology for gold standard behavior-based clinical measures of consciousness, and reframe our current models of DOC by stressing the different links tying thalamic mechanisms to willful behavior and extrathalamic mechanisms to behavioral (and electrocortical) arousal.

Risk, diagnostic error, and the clinical science of consciousness.

In recent years, a number of new neuroimaging techniques have detected covert awareness in some patients previously thought to be in a vegetative state/unresponsive wakefulness syndrome. This raises worries for patients, families, and physicians, as it indicates that the existing diagnostic error rate in this patient group is higher than assumed. Recent research on a subset of these techniques, called active paradigms, suggests that false positive and false negative findings may result from applying different statistical methods to patient data. Due to the nature of this research, these errors may be unavoidable, and may draw into question the use of active paradigms in the clinical setting. We argue that false positive and false negative findings carry particular moral risks, which may bear on investigators' decisions to use certain methods when independent means for estimating their clinical utility are absent. We review and critically analyze this methodological problem as it relates to both fMRI and EEG active paradigms. We conclude by drawing attention to three common clinical scenarios where the risk of diagnostic error may be most pronounced in this patient group.

Thalamo-frontal connectivity mediates top-down cognitive functions in disorders of consciousness.

OBJECTIVE: We employed functional MRI (fMRI) to assess whether (1) patients with disorders of consciousness (DOC) retain the ability to willfully engage in top-down processing and (2) what neurophysiologic factors distinguish patients who can demonstrate this ability from patients who cannot. METHODS: Sixteen volunteers, 8 patients in vegetative state (VS), 16 minimally conscious patients (MCS), and 4 exit from MCS (eMCS) patients were enrolled in a prospective cross-sectional fMRI study. Participants performed a target detection task in which they counted the number of times a (changing) target word was presented amidst a set of distractors. RESULTS: Three of 8 patients diagnosed as being in a VS exhibited significant activations in response to the task, thereby demonstrating a state of consciousness. Differential activations across tasks were also observed in 6 MCS patients and 1 eMCS patient. A psycho-physiologic interaction analysis revealed that the main factor distinguishing patients who responded to the task from those who did not was a greater connectivity between the anterior section of thalamus and prefrontal cortex. CONCLUSIONS: In our sample of patients, the dissociation between overt behavior observable in clinical assessments and residual cognitive faculties is prevalent among DOC patients (37%). A substantial number of patients, including some diagnosed with VS, can demonstrate willful engagement in top-down cognition. While neuroimaging data are not the same as observable behavior, this suggests that the mental status of some VS patients exceeds what can be appreciated clinically. Furthermore, thalamo-frontal circuits might be crucial to sustaining top-down functions.

Multiple tasks and neuroimaging modalities increase the likelihood of detecting covert awareness in patients with disorders of consciousness.

Minimal or inconsistent behavioral responses to command make it challenging to accurately diagnose the level of awareness of a patient with a Disorder of consciousness (DOC). By identifying markers of mental imagery being covertly performed to command, functional neuroimaging (fMRI), electroencephalography (EEG) has shown that some of these patients are aware despite their lack of behavioral responsiveness. We report the findings of behavioral, fMRI, and EEG approaches to detecting command-following in a group of patients with DOC. From an initial sample of 14 patients, complete data across all tasks was obtained in six cases. Behavioral evaluations were performed with the Coma Recovery Scale-Revised. Both fMRI and EEG evaluations involved the completion of previously validated mental imagery tasks-i.e., motor imagery (EEG and fMRI) and spatial navigation imagery (fMRI). One patient exhibited statistically significant evidence of motor imagery in both the fMRI and EEG tasks, despite being unable to follow commands behaviorally. Two behaviorally non-responsive patients produced appropriate activation during the spatial navigation fMRI task. However, neither of these patients successfully completed the motor imagery tasks, likely due to specific motor area damage in at least one of these cases. A further patient demonstrated command following only in the EEG motor imagery task, and two patients did not demonstrate command following in any of the behavioral, EEG, or fMRI assessments. Due to the heterogeneity of etiology and pathology in this group, DOC patients vary in terms of their suitability for some forms of neuroimaging, the preservation of specific neural structures, and the cognitive resources that may be available to them. Assessments of a range of cognitive abilities supported by spatially-distinct brain regions and indexed by multiple neural signatures are therefore required in order to accurately characterize a patient's level of residual cognition and awareness.

The reliability of the N400 in single subjects: implications for patients with disorders of consciousness.

Functional neuroimaging assessments of residual cognitive capacities, including those that support language, can improve diagnostic and prognostic accuracy in patients with disorders of consciousness. Due to the portability and relative inexpensiveness of electroencephalography, the N400 event-related potential component has been proposed as a clinically valid means to identify preserved linguistic function in non-communicative patients. Across three experiments, we show that changes in both stimuli and task demands significantly influence the probability of detecting statistically significant N400 effects - that is, the difference in N400 amplitudes caused by the experimental manipulation. In terms of task demands, passively heard linguistic stimuli were significantly less likely to elicit N400 effects than task-relevant stimuli. Due to the inability of the majority of patients with disorders of consciousness to follow task commands, the insensitivity of passive listening would impede the identification of residual language abilities even when such abilities exist. In terms of stimuli, passively heard normatively associated word pairs produced the highest detection rate of N400 effects (50% of the participants), compared with semantically-similar word pairs (0%) and high-cloze sentences (17%). This result is consistent with a prediction error account of N400 magnitude, with highly predictable targets leading to smaller N400 waves, and therefore larger N400 effects. Overall, our data indicate that non-repeating normatively associated word pairs provide the highest probability of detecting single-subject N400s during passive listening, and may thereby provide a clinically viable means of assessing residual linguistic function. We also show that more liberal analyses may further increase the detection-rate, but at the potential cost of increased false alarms.

The clinical utility of fMRI for identifying covert awareness in the vegetative state: a comparison of sensitivity between 3T and 1.5T.

In the last few years, mental imagery fMRI paradigms have been used successfully to identify covert command-following and awareness in some patients who are thought to be entirely vegetative. However, to date there is only evidence supporting their use at magnetic fields of 3T, which limits their applicability in clinical settings where lower field strengths are typically used. Here, we test the 'gold standard' fMRI paradigm for detecting residual awareness in non-responsive patients by comparing its sensitivity at 1.5T and 3T in the same group of healthy volunteers. We were able to successfully detect brain activity showing command-following in most participants at both 3T and 1.5T, with similar reliability. These results demonstrate that fMRI assessment of covert awareness is clinically viable and therefore justify a broader use of these methods in standard assessments in severely brain injured patients.

Complexity and familiarity enhance single-trial detectability of imagined movements with electroencephalography.

OBJECTIVE: We sought to determine whether the sensorimotor rhythms (SMR) elicited during motor imagery (MI) of complex and familiar actions could be more reliably detected with electroencephalography (EEG), and subsequently classified on a single-trial basis, than those elicited during relatively simpler imagined actions. METHODS: Groups of healthy volunteers, including experienced pianists and ice hockey players, performed MI of varying complexity and familiarity. Their electroencephalograms were recorded and compared using brain-computer interface (BCI) approaches and spectral analyses. RESULTS: Relative to simple MI, significantly more participants produced classifiable SMR for complex MI. During MI of performance of a complex musical piece, the EEG of the experienced pianists was classified significantly more accurately than during MI of performance of a simpler musical piece. The accuracy of EEG classification was also significantly more sustained during complex MI. CONCLUSION: MI of complex actions results in EEG responses that are more reliably classified for more individuals than MI of relatively simpler actions, and familiarity with actions enhances these responses in some cases. SIGNIFICANCE: The accuracy of SMR-based BCIs in non-communicative patients may be improved by employing familiar and complex actions. Increased sensitivity to MI may also improve diagnostic accuracy for severely brain-injured patients in a vegetative state.

Into the groove: can rhythm influence Parkinson's disease?

Previous research has noted that music can improve gait in several pathological conditions, including Parkinson's disease, Huntington's disease and stroke. Current research into auditory-motor interactions and the neural bases of musical rhythm perception has provided important insights for developing potential movement therapies. Specifically, neuroimaging studies show that rhythm perception activates structures within key motor networks, such as premotor and supplementary motor areas, basal ganglia and the cerebellum - many of which are compromised to varying degrees in Parkinson's disease. It thus seems likely that automatic engagement of motor areas during rhythm perception may be the connecting link between music and motor improvements in Parkinson's disease. This review seeks to describe the link, address core questions about its underlying mechanisms, and examine whether it can be utilized as a compensatory mechanism.

Making every word count for nonresponsive patients.

IMPORTANCE: Despite the apparent absence of external signs of consciousness, a significant small proportion of patients with disorders of consciousness can respond to commands by willfully modulating their brain activity, even respond to yes or no questions, by performing mental imagery tasks. However, little is known about the mental life of such responsive patients, for example, with regard to whether they can have coherent thoughts or selectively maintain attention to specific events in their environment. The ability to selectively pay attention would provide evidence of a patient's preserved cognition and a method for brain-based communication, thus far untested with functional magnetic resonance imaging in this patient group. OBJECTIVE: To test whether selective auditory attention can be used to detect conscious awareness and communicate with behaviorally nonresponsive patients. DESIGN, SETTING, AND PARTICIPANTS: Case study performed in 3 patients with severe brain injury, 2 diagnosed as being in a minimally conscious state and 1 as being in a vegetative state. The patients constituted a convenience sample. MAIN OUTCOMES AND MEASURES: Functional magnetic resonance imaging data were acquired as the patients were asked to selectively attend to auditory stimuli, thereby conveying their ability to follow commands and communicate. RESULTS: All patients demonstrated command following according to instructions. Two patients (1 in a minimally conscious state and 1 in a vegetative state) were also able to guide their attention to repeatedly communicate correct answers to binary (yes or no) questions. CONCLUSIONS AND RELEVANCE: To our knowledge, we show for the first time with functional magnetic resonance imaging that behaviorally nonresponsive patients can use selective auditory attention to convey their ability to follow commands and communicate. One patient in a minimally conscious state was able to use attention to establish functional communication in the scanner, despite his inability to produce any communication responses in repeated bedside examinations. More important, 1 patient, who had been in a vegetative state for 12 years before the scanning and subsequent to it, was able to use attention to correctly communicate answers to several binary questions. The technique may be useful in establishing basic communication with patients who appear unresponsive to bedside examinations and cannot respond with existing neuroimaging methods.

Expectation and attention in hierarchical auditory prediction.

Hierarchical predictive coding suggests that attention in humans emerges from increased precision in probabilistic inference, whereas expectation biases attention in favor of contextually anticipated stimuli. We test these notions within auditory perception by independently manipulating top-down expectation and attentional precision alongside bottom-up stimulus predictability. Our findings support an integrative interpretation of commonly observed electrophysiological signatures of neurodynamics, namely mismatch negativity (MMN), P300, and contingent negative variation (CNV), as manifestations along successive levels of predictive complexity. Early first-level processing indexed by the MMN was sensitive to stimulus predictability: here, attentional precision enhanced early responses, but explicit top-down expectation diminished it. This pattern was in contrast to later, second-level processing indexed by the P300: although sensitive to the degree of predictability, responses at this level were contingent on attentional engagement and in fact sharpened by top-down expectation. At the highest level, the drift of the CNV was a fine-grained marker of top-down expectation itself. Source reconstruction of high-density EEG, supported by intracranial recordings, implicated temporal and frontal regions differentially active at early and late levels. The cortical generators of the CNV suggested that it might be involved in facilitating the consolidation of context-salient stimuli into conscious perception. These results provide convergent empirical support to promising recent accounts of attention and expectation in predictive coding.