Neural correlates of ongoing conscious experience: both task-unrelatedness and stimulus-independence are related to default network activity

The default mode network (DMN) is a set of brain regions that consistently shows higher activity at rest compared to tasks requiring sustained focused attention toward externally presented stimuli. The cognitive processes that the DMN possibly underlies remain a matter of debate. It has alternately been proposed that DMN activity reflects unfocused attention toward external stimuli or the occurrence of internally generated thoughts. The present study aimed at clarifying this issue by investigating the neural correlates of the various kinds of conscious experiences that can occur during task performance. Four classes of conscious experiences (i.e., being fully focused on the task, distractions by irrelevant sensations/perceptions, interfering thoughts related to the appraisal of the task, and mind-wandering) that varied along two dimensions ("task-relatedness" and "stimulus-dependency") were sampled using thought-probes while the participants performed a go/no-go task. Analyses performed on the intervals preceding each probe according to the reported subjective experience revealed that both dimensions are relevant to explain activity in several regions of the DMN, namely the medial prefrontal cortex, posterior cingulate cortex/precuneus, and posterior inferior parietal lobe. Notably, an additive effect of the two dimensions was demonstrated for midline DMN regions. On the other hand, lateral temporal regions (also part of the DMN) were specifically related to stimulus-independent reports. These results suggest that midline DMN regions underlie cognitive processes that are active during both internal thoughts and external unfocused attention. They also strengthen the view that the DMN can be fractionated into different subcomponents and reveal the necessity to consider both the stimulus-dependent and the task-related dimensions of conscious experiences when studying the possible functional roles of the DMN.     

A core system for the implementation of task sets

When performing tasks, humans are thought to adopt task sets that configure moment-to-moment data processing. Recently developed mixed blocked/event-related designs allow task set-related signals to be extracted in fMRI experiments, including activity related to cues that signal the beginning of a task block, "set-maintenance" activity sustained for the duration of a task block, and event-related signals for different trial types. Data were conjointly analyzed from mixed design experiments using ten different tasks and 183 subjects. Dorsal anterior cingulate cortex/medial superior frontal cortex (dACC/msFC) and bilateral anterior insula/frontal operculum (aI/fO) showed reliable start-cue and sustained activations across all or nearly all tasks. These regions also carried the most reliable error-related signals in a subset of tasks, suggesting that the regions form a "core" task-set system. Prefrontal regions commonly related to task control carried task-set signals in a smaller subset of tasks and lacked convergence across signal types.     

Discrimination task reveals differences in neural bases of tinnitus and hearing impairment

We investigated auditory perception and cognitive processing in individuals with chronic tinnitus or hearing loss using functional magnetic resonance imaging (fMRI). Our participants belonged to one of three groups: bilateral hearing loss and tinnitus (TIN), bilateral hearing loss without tinnitus (HL), and normal hearing without tinnitus (NH). We employed pure tones and frequency-modulated sweeps as stimuli in two tasks: passive listening and active discrimination. All subjects had normal hearing through 2 kHz and all stimuli were low-pass filtered at 2 kHz so that all participants could hear them equally well. Performance was similar among all three groups for the discrimination task. In all participants, a distributed set of brain regions including the primary and non-primary auditory cortices showed greater response for both tasks compared to rest. Comparing the groups directly, we found decreased activation in the parietal and frontal lobes in the participants with tinnitus compared to the HL group and decreased response in the frontal lobes relative to the NH group. Additionally, the HL subjects exhibited increased response in the anterior cingulate relative to the NH group. Our results suggest that a differential engagement of a putative auditory attention and short-term memory network, comprising regions in the frontal, parietal and temporal cortices and the anterior cingulate, may represent a key difference in the neural bases of chronic tinnitus accompanied by hearing loss relative to hearing loss alone.     

Same modulation but different starting points: performance modulates age differences in inferior frontal cortex activity during word-retrieval

The neural basis of word-retrieval deficits in normal aging has rarely been assessed and the few previous functional imaging studies found enhanced activity in right prefrontal areas in healthy older compared to younger adults. However, more pronounced right prefrontal recruitment has primarily been observed during challenging task conditions. Moreover, increased task difficulty may result in enhanced activity in the ventral inferior frontal gyrus (vIFG) bilaterally in younger participants as well. Thus, the question arises whether increased activity in older participants represents an age-related phenomenon or reflects task difficulty effects. In the present study, we manipulated task difficulty during overt semantic and phonemic word-generation and used functional magnetic resonance imaging to assess activity patterns in the vIFG in healthy younger and older adults (N = 16/group; mean age: 24 vs. 69 years). Both groups produced fewer correct responses during the more difficult task conditions. Overall, older participants produced fewer correct responses and showed more pronounced task-related activity in the right vIFG. However, increased activity during the more difficult conditions was found in both groups. Absolute degree of activity was correlated with performance across groups, tasks and difficulty levels. Activity modulation (difficult vs. easy conditions) was correlated with the respective drop in performance across groups and tasks. In conclusion, vIFG activity levels and modulation of activity were mediated by performance accuracy in a similar way in both groups. Group differences in the right vIFG activity were explained by performance accuracy which needs to be considered in future functional imaging studies of healthy and pathological aging.     

Functional Activation during the Rapid Visual Information Processing Task in a Middle Aged Cohort: An fMRI Study

The Rapid Visual Information Processing (RVIP) task, a serial discrimination task where task performance believed to reflect sustained attention capabilities, is widely used in behavioural research and increasingly in neuroimaging studies. To date, functional neuroimaging research into the RVIP has been undertaken using block analyses, reflecting the sustained processing involved in the task, but not necessarily the transient processes associated with individual trial performance. Furthermore, this research has been limited to young cohorts. This study assessed the behavioural and functional magnetic resonance imaging (fMRI) outcomes of the RVIP task using both block and event-related analyses in a healthy middle aged cohort (mean age = 53.56 years, n = 16). The results show that the version of the RVIP used here is sensitive to changes in attentional demand processes with participants achieving a 43% accuracy hit rate in the experimental task compared with 96% accuracy in the control task. As shown by previous research, the block analysis revealed an increase in activation in a network of frontal, parietal, occipital and cerebellar regions. The event related analysis showed a similar network of activation, seemingly omitting regions involved in the processing of the task (as shown in the block analysis), such as occipital areas and the thalamus, providing an indication of a network of regions involved in correct trial performance. Frontal (superior and inferior frontal gryi), parietal (precuenus, inferior parietal lobe) and cerebellar regions were shown to be active in both the block and event-related analyses, suggesting their importance in sustained attention/vigilance. These networks and the differences between them are discussed in detail, as well as implications for future research in middle aged cohorts.     

Neural Substrates for Semantic Memory of Familiar Songs: Is There an Interface between Lyrics and Melodies?

Findings on song perception and song production have increasingly suggested that common but partially distinct neural networks exist for processing lyrics and melody. However, the neural substrates of song recognition remain to be investigated. The purpose of this study was to examine the neural substrates involved in the accessing “song lexicon” as corresponding to a representational system that might provide links between the musical and phonological lexicons using positron emission tomography (PET). We exposed participants to auditory stimuli consisting of familiar and unfamiliar songs presented in three ways: sung lyrics (song), sung lyrics on a single pitch (lyrics), and the sung syllable ‘la’ on original pitches (melody). The auditory stimuli were designed to have equivalent familiarity to participants, and they were recorded at exactly the same tempo. Eleven right-handed nonmusicians participated in four conditions: three familiarity decision tasks using song, lyrics, and melody and a sound type decision task (control) that was designed to engage perceptual and prelexical processing but not lexical processing. The contrasts (familiarity decision tasks versus control) showed no common areas of activation between lyrics and melody. This result indicates that essentially separate neural networks exist in semantic memory for the verbal and melodic processing of familiar songs. Verbal lexical processing recruited the left fusiform gyrus and the left inferior occipital gyrus, whereas melodic lexical processing engaged the right middle temporal sulcus and the bilateral temporo-occipital cortices. Moreover, we found that song specifically activated the left posterior inferior temporal cortex, which may serve as an interface between verbal and musical representations in order to facilitate song recognition.     

Neural Effects of Auditory Distraction on Visual Attention in Schizophrenia

Sensory flooding, particularly during auditory stimulation, is a common problem for patients with schizophrenia. The functional consequences of this impairment during cross-modal attention tasks, however, are unclear. The purpose of this study was to examine how auditory distraction differentially affects task-associated response during visual attention in patients and healthy controls. To that end, 21 outpatients with schizophrenia and 23 healthy comparison subjects performed a visual attention task in the presence or absence of distracting, environmentally relevant “urban” noise while undergoing functional magnetic resonance imaging at 3T. The task had two conditions (difficult and easy); task-related neural activity was defined as difficult – easy. During task performance, a significant distraction (noise or silence) by group (patient or control) interaction was observed in the left dorsolateral prefrontal cortex, right hippocampus, left temporoparietal junction, and right fusiform gyrus, with patients showing relative hypoactivation during noise compared to controls. In patients, the ability to recruit the dorsolateral prefrontal cortex during the task in noise was negatively correlated with the effect of noise on reaction time. Clinically, the ability to recruit the fusiform gyrus during the task in noise was negatively correlated with SANS affective flattening score, and hippocampal recruitment during the task in noise was positively correlated with global functioning. In conclusion, schizophrenia may be associated with abnormalities in neural response during visual attention tasks in the presence of cross-modal noise distraction. These response differences may predict global functioning in the illness, and may serve as a biomarker for therapeutic development.     

Saccadic Eye Movements in Anorexia Nervosa

Background

Anorexia Nervosa (AN) has a mortality rate among the highest of any mental illness, though the factors involved in the condition remain unclear. Recently, the potential neurobiological underpinnings of the condition have become of increasing interest. Saccadic eye movement tasks have proven useful in our understanding of the neurobiology of some other psychiatric illnesses as they utilise known brain regions, but to date have not been examined in AN. The aim of this study was to investigate whether individuals with AN differ from healthy individuals in performance on a range of saccadic eye movements tasks.

Methods

24 females with AN and 25 healthy individuals matched for age, gender and premorbid intelligence participated in the study. Participants were required to undergo memory-guided and self-paced saccade tasks, and an interleaved prosaccade/antisaccade/no-go saccade task while undergoing functional magnetic resonance imaging (fMRI).

Results

AN participants were found to make prosaccades of significantly shorter latency than healthy controls. AN participants also made an increased number of inhibitory errors on the memory-guided saccade task. Groups did not significantly differ in antisaccade, no-go saccade or self-paced saccade performance, or fMRI findings.

Discussion

The results suggest a potential role of GABA in the superior colliculus in the psychopathology of AN.     

Functional Difference between Sustained and Transient Modulations of Cognitive Control in the Simon Task: Evidence from False Alarm Responses on No-Go Trials

Cognitive control in response compatibility tasks is modulated by the task context. Two types of contextual modulations have been demonstrated; sustained (block-wise) and transient (trial-by-trial). Recent research suggests that these modulations have different underlying mechanisms. This study presents new evidence supporting this claim by comparing false alarm (FA) responses on no-go trials of the Simon task between the sustained and transient contexts. In Experiment 1, the sustained context was manipulated so that a block included a larger number of incongruent trials. Results showed that participants made more FA responses by the hand opposite to the stimulus location. This suggests a generation of response bias in which the task-irrelevant location information is utilized in a reversed manner (i.e., to respond with the right hand to a stimulus presented on the left side and vice versa). Next, Experiment 2 examined the effect of the transient context and found that overall FA rate was lower when a no-go trial was preceded by an incongruent trial than by a congruent trial, whereas such response bias as that shown in Experiment 1 was not demonstrated. This suggests that the transient conflict context enhances inhibition of the task-irrelevant process but does not make the task-irrelevant information actively usable. Based on these results, we propound two types of cognitive control modulations as adaptive behaviors: response biasing based on utilization of the task-irrelevant information under the sustained conflict context and transient enhancement of inhibition of the task-irrelevant process based on the online conflict monitoring.     

Trying to detect taste in a tasteless solution: modulation of early gustatory cortex by attention to taste

Selective attention is thought to be associated with enhanced processing in modality-specific cortex. We used functional magnetic resonance imaging to evaluate brain response during a taste detection task. We demonstrate that trying to detect the presence of taste in a tasteless solution results in enhanced activity in insula and overlying operculum. The same task does not recruit orbitofrontal cortex (OFC). Instead, the OFC responds preferentially during receipt of an unpredicted taste stimulus. These findings demonstrate functional specialization of taste cortex in which the insula and the overlying operculum are recruited during taste detection and selective attention to taste, and the OFC is recruited during receipt of an unpredicted taste stimulus.     

Rule-guided executive control of response inhibition: functional topography of the inferior frontal cortex

Background

The human inferior frontal cortex (IFC) is a large heterogeneous structure with distinct cytoarchitectonic subdivisions and fiber connections. It has been found involved in a wide range of executive control processes from target detection, rule retrieval to response control. Since these processes are often being studied separately, the functional organization of executive control processes within the IFC remains unclear.

Methodology/Principal Findings

We conducted an fMRI study to examine the activities of the subdivisions of IFC during the presentation of a task cue (rule retrieval) and during the performance of a stop-signal task (requiring response generation and inhibition) in comparison to a not-stop task (requiring response generation but not inhibition). We utilized a mixed event-related and block design to separate brain activity in correspondence to transient control processes from rule-related and sustained control processes. We found differentiation in control processes within the IFC. Our findings reveal that the bilateral ventral-posterior IFC/anterior insula are more active on both successful and unsuccessful stop trials relative to not-stop trials, suggesting their potential role in the early stage of stopping such as triggering the stop process. Direct countermanding seems to be outside of the IFC. In contrast, the dorsal-posterior IFC/inferior frontal junction (IFJ) showed transient activity in correspondence to the infrequent presentation of the stop signal in both tasks and the left anterior IFC showed differential activity in response to the task cues. The IFC subdivisions also exhibited similar but distinct patterns of functional connectivity during response control.

Conclusions/Significance

Our findings suggest that executive control processes are distributed across the IFC and that the different subdivisions of IFC may support different control operations through parallel cortico-cortical and cortico-striatal circuits.     

Task-switching Cost and Intrinsic Functional Connectivity in the Human Brain: Toward Understanding Individual Differences in Cognitive Flexibility

The human ability to flexibly alternate between tasks (i.e., task-switching) represents a critical component of cognitive control. Many functional magnetic resonance imaging (fMRI) studies have explored the neural basis of the task-switching. However, no study to date has examined how individual differences in intrinsic functional architecture of the human brain are related to that of the task-switching. In the present study, we took 11 task-switching relevant areas from a meta-analysis study as the regions of interests (ROIs) and estimated their intrinsic functional connectivity (iFC) with the whole brain. This procedure was repeated for 32 healthy adults based upon their fMRI scans during resting-state (rfMRI) to investigate the correlations between switching cost and the iFC strength across these participants. This analysis found that switch cost was negatively correlated with a set of iFC involved ROIs including left inferior frontal junction, bilateral superior posterior parietal cortex, left precuneus, bilateral inferior parietal lobule, right middle frontal gyrus and bilateral middle occipital gyrus. These connectivity profiles represent an intrinsic functional architecture of task-switching where the left inferior frontal junction plays a hub role in this brain-behavior association. These findings are highly reproducible in another validation independent sample and provide a novel perspective for understanding the neural basis of individual differences in task-switching behaviors reflected in the intrinsic architecture of the human brain.     

Factors Limiting Performance in a Multitone Intensity-Discrimination Task: Disentangling Non-Optimal Decision Weights and Increased Internal Noise

To identify factors limiting performance in multitone intensity discrimination, we presented sequences of five pure tones alternating in level between loud (85 dB SPL) and soft (30, 55, or 80 dB SPL). In the “overall-intensity task”, listeners detected a level increment on all of the five tones. In the “masking task”, the level increment was imposed only on the soft tones, rendering the soft tones targets and loud tones task-irrelevant maskers. Decision weights quantifying the importance of the five tone levels for the decision were estimated using methods of molecular psychophysics. Compatible with previous studies, listeners placed higher weights on the loud tones than on the soft tones in the overall-intensity condition. In the masking task, the decisions were systematically influenced by the to-be-ignored loud tones (maskers). Using a maximum-likelihood technique, we estimated the internal noise variance and tested whether the internal noise was higher in the alternating-level five-tone sequences than in sequences presenting only the soft or only the loud tones. For the overall-intensity task, we found no evidence for increased internal noise, but listeners applied suboptimal decision weights. These results are compatible with the hypothesis that the presence of the loud tones does not impair the precision of the representation of the intensity of the soft tones available at the decision stage, but that this information is not used in an optimal fashion due to a difficulty in attending to the soft tones. For the masking task, in some cases our data indicated an increase in internal noise. Additionally, listeners applied suboptimal decision weights. The maximum-likelihood analyses we developed should also be useful for other tasks or other sensory modalities.     

Gustatory imagery reveals functional connectivity from the prefrontal to insular cortices traced with magnetoencephalography

Our experience and prejudice concerning food play an important role in modulating gustatory information processing; gustatory memory stored in the central nervous system influences gustatory information arising from the peripheral nervous system. We have elucidated the mechanism of the “top-down” modulation of taste perception in humans using functional magnetic resonance imaging (fMRI) and demonstrated that gustatory imagery is mediated by the prefrontal (PFC) and insular cortices (IC). However, the temporal order of activation of these brain regions during gustatory imagery is still an open issue. To explore the source of “top-down” signals during gustatory imagery tasks, we analyzed the temporal activation patterns of activated regions in the cerebral cortex using another non-invasive brain imaging technique, magnetoencephalography (MEG). Gustatory imagery tasks were presented by words (Letter G-V) or pictures (Picture G-V) of foods/beverages, and participants were requested to recall their taste. In the Letter G-V session, 7/9 (77.8%) participants showed activation in the IC with a latency of 401.7±34.7 ms (n = 7) from the onset of word exhibition. In 5/7 (71.4%) participants who exhibited IC activation, the PFC was activated prior to the IC at a latency of 315.2±56.5 ms (n = 5), which was significantly shorter than the latency to the IC activation. In the Picture G-V session, the IC was activated in 6/9 (66.7%) participants, and only 1/9 (11.1%) participants showed activation in the PFC. There was no significant dominance between the right and left IC or PFC during gustatory imagery. These results support those from our previous fMRI study in that the Letter G-V session rather than the Picture G-V session effectively activates the PFC and IC and strengthen the hypothesis that the PFC mediates “top-down” control of retrieving gustatory information from the storage of long-term memories and in turn activates the IC.     

Toward Probabilistic Diagnosis and Understanding of Depression Based on Functional MRI Data Analysis with Logistic Group LASSO

Diagnosis of psychiatric disorders based on brain imaging data is highly desirable in clinical applications. However, a common problem in applying machine learning algorithms is that the number of imaging data dimensions often greatly exceeds the number of available training samples. Furthermore, interpretability of the learned classifier with respect to brain function and anatomy is an important, but non-trivial issue. We propose the use of logistic regression with a least absolute shrinkage and selection operator (LASSO) to capture the most critical input features. In particular, we consider application of group LASSO to select brain areas relevant to diagnosis. An additional advantage of LASSO is its probabilistic output, which allows evaluation of diagnosis certainty. To verify our approach, we obtained semantic and phonological verbal fluency fMRI data from 31 depression patients and 31 control subjects, and compared the performances of group LASSO (gLASSO), and sparse group LASSO (sgLASSO) to those of standard LASSO (sLASSO), Support Vector Machine (SVM), and Random Forest. Over 90% classification accuracy was achieved with gLASSO, sgLASSO, as well as SVM; however, in contrast to SVM, LASSO approaches allow for identification of the most discriminative weights and estimation of prediction reliability. Semantic task data revealed contributions to the classification from left precuneus, left precentral gyrus, left inferior frontal cortex (pars triangularis), and left cerebellum (c rus1). Weights for the phonological task indicated contributions from left inferior frontal operculum, left post central gyrus, left insula, left middle frontal cortex, bilateral middle temporal cortices, bilateral precuneus, left inferior frontal cortex (pars triangularis), and left precentral gyrus. The distribution of normalized odds ratios further showed, that predictions with absolute odds ratios higher than 0.2 could be regarded as certain.     

A Brain Motor Control Assessment (BMCA) Protocol for Upper Limb Function

The Brain Motor Control Assessment (BMCA) protocol is a surface electromyography (sEMG)-based measure of motor output from central nervous system during a variety of reflex and voluntary motor tasks performed under strictly controlled conditions. The aim of this study was to evaluate the BMCA protocol for upper limb with the addition of shoulder voluntary tasks. The voluntary response index (VRI) was calculated from quantitative analysis of sEMG data during defined voluntary movement in neurologically intact people for comparison with that of patients after neurological injuries. The BMCA protocol included one bilateral and 4 unilateral voluntary tasks at different joints of both arms. The VRI, measured from 19 neurologically intact participants, comprises the total muscle activity recorded for the voluntary motor task (magnitude). The calculated similarity index (SI) for each phase of each task show the similarity of “the distribution of activity across the recorded muscles” for that task in this group off participants. Results: The VRI magnitude values from right and left sides for different tasks showed no significant difference (ANOVA: F_Side: 0.09, P = 0.77). Therefore these values were pooled before calculating SI. SI values were higher for tasks against gravity: elbow flexion (0.99±0.03), wrist flexion with palm up (0.98±0.03) and wrist extension with palm down (0.97±0.07). On the other hand, the SI values were the lowest for bilateral shoulder abduction (0.84±0.08) and shoulder adduction (0.84±0.08). Conclusion: To validate this index for clinical use, serial studies on patients with neurological impairments should be performed. Tasks involving movement against gravity may be more suitable in future BMCAs.     

Extracting Multiscale Pattern Information of fMRI Based Functional Brain Connectivity with Application on Classification of Autism Spectrum Disorders

We employed a multi-scale clustering methodology known as “data cloud geometry” to extract functional connectivity patterns derived from functional magnetic resonance imaging (fMRI) protocol. The method was applied to correlation matrices of 106 regions of interest (ROIs) in 29 individuals with autism spectrum disorders (ASD), and 29 individuals with typical development (TD) while they completed a cognitive control task. Connectivity clustering geometry was examined at both “fine” and “coarse” scales. At the coarse scale, the connectivity clustering geometry produced 10 valid clusters with a coherent relationship to neural anatomy. A supervised learning algorithm employed fine scale information about clustering motif configurations and prevalence, and coarse scale information about intra- and inter-regional connectivity; the algorithm correctly classified ASD and TD participants with sensitivity of and specificity of . Most of the predictive power of the logistic regression model resided at the level of the fine-scale clustering geometry, suggesting that cellular versus systems level disturbances are more prominent in individuals with ASD. This article provides validation for this multi-scale geometric approach to extracting brain functional connectivity pattern information and for its use in classification of ASD.     

Reading a Suspenseful Literary Text Activates Brain Areas Related to Social Cognition and Predictive Inference

Stories can elicit powerful emotions. A key emotional response to narrative plots (e.g., novels, movies, etc.) is suspense. Suspense appears to build on basic aspects of human cognition such as processes of expectation, anticipation, and prediction. However, the neural processes underlying emotional experiences of suspense have not been previously investigated. We acquired functional magnetic resonance imaging (fMRI) data while participants read a suspenseful literary text (E.T.A. Hoffmann''s “The Sandman”) subdivided into short text passages. Individual ratings of experienced suspense obtained after each text passage were found to be related to activation in the medial frontal cortex, bilateral frontal regions (along the inferior frontal sulcus), lateral premotor cortex, as well as posterior temporal and temporo-parietal areas. The results indicate that the emotional experience of suspense depends on brain areas associated with social cognition and predictive inference.     

SUBJECTIVE PERCEPTIONS OF THE EFFECTS OF SUSTAINED PERFORMANCE UNDER SLEEP-DEPRIVATION CONDITIONS

In today's society, numerous situations arise in which sleep deprivation is a common occurrence. Subjective perceptions are a vital component to understanding the effects of sustained performance during sleep deprivation, as they may be the first indication of the effects of sustained performance or sleep deprivation on the individual. Using the theoretical framework of the Controlled Attention Model, this study examined the effects of 16?h of sustained performance under 28?h of acute sleep deprivation on perceived effort, motivation, and stress of 24 participants while completing a complex cognitive and a simple vigilance task. Perceived effort increased for both tasks, with higher effort reported on the cognitive than the vigilance task at the beginning of the experimental period, but with higher effort reported on the vigilance than the cognitive task at the end. Subjective motivation decreased for both tasks, with significantly higher levels of motivation on the cognitive than the vigilance task. Perceived stress did not change for either task. Results suggest that functioning under sustained performance and sleep-deprivation conditions affects subjective perceptions differently for cognitive versus vigilance tasks. The controlled attention model offers one means of understanding how different tasks could affect a person's subjective perceptions and ability to perform, in that different levels of controlled attention are required for the two tasks. (Author correspondence: hodle@gettysburg.edu)