Seeking Optimal Region-Of-Interest (ROI) Single-Value Summary Measures for fMRI Studies in Imaging Genetics.

A data-driven hypothesis-free genome-wide association (GWA) approach in imaging genetics studies allows screening the entire genome to discover novel genes that modulate brain structure, chemistry, and function. However, a whole brain voxel-wise analysis approach in such genome-wide based imaging genetic studies can be computationally intense and also likely has low statistical power since a stringent multiple comparisons correction is needed for searching over the entire genome and brain. In imaging genetics with functional magnetic resonance imaging (fMRI) phenotypes, since many experimental paradigms activate focal regions that can be pre-specified based on a priori knowledge, reducing the voxel-wise search to single-value summary measures within a priori ROIs could prove efficient and promising. The goal of this investigation is to evaluate the sensitivity and reliability of different single-value ROI summary measures and provide guidance in future work. Four different fMRI databases were tested and comparisons across different groups (patients with schizophrenia, their siblings, vs. normal control subjects; across genotype groups) were conducted. Our results show that four of these measures, particularly those that represent values from the top most-activated voxels within an ROI are more powerful at reliably detecting group differences and generating greater effect sizes than the others.

Denoising the speaking brain: toward a robust technique for correcting artifact-contaminated fMRI data under severe motion.

A comprehensive set of methods based on spatial independent component analysis (sICA) is presented as a robust technique for artifact removal, applicable to a broad range of functional magnetic resonance imaging (fMRI) experiments that have been plagued by motion-related artifacts. Although the applications of sICA for fMRI denoising have been studied previously, three fundamental elements of this approach have not been established as follows: 1) a mechanistically-based ground truth for component classification; 2) a general framework for evaluating the performance and generalizability of automated classifiers; and 3) a reliable method for validating the effectiveness of denoising. Here we perform a thorough investigation of these issues and demonstrate the power of our technique by resolving the problem of severe imaging artifacts associated with continuous overt speech production. As a key methodological feature, a dual-mask sICA method is proposed to isolate a variety of imaging artifacts by directly revealing their extracerebral spatial origins. It also plays an important role for understanding the mechanistic properties of noise components in conjunction with temporal measures of physical or physiological motion. The potentials of a spatially-based machine learning classifier and the general criteria for feature selection have both been examined, in order to maximize the performance and generalizability of automated component classification. The effectiveness of denoising is quantitatively validated by comparing the activation maps of fMRI with those of positron emission tomography acquired under the same task conditions. The general applicability of this technique is further demonstrated by the successful reduction of distance-dependent effect of head motion on resting-state functional connectivity.

Neurophysiological correlates of age-related changes in working memory updating.

Normal aging is associated with a gradual decline in executive functions such as set-shifting, inhibition, and updating, along with a progressive decline of neurotransmitter systems including the dopamine system. Modulation from the dopamine system is thought to be critical for the gating of information during working memory. Given the known relationships between executive aging, cognition, and dopamine, this study aims to explore the neurobiology underlying age-related changes in working memory updating using fMRI with healthy subjects from across the adult age spectrum. Our results indicate that older age is associated with poorer performance, reduced meso-cortico-striatal activation, and reduced functional coupling between the caudate and the VLPFC during the updating task. Additionally, caudate activation is associated with improved accuracy and VLPFC activation with faster reaction times in the full sample. Thus, older subjects' under-recruitment of and reduced functional coupling between these regions may specifically underlie age-related changes in working memory updating. These results are consistent with computational models of executive cognition and dopamine-mediated age-related cognitive decline.

Control of working memory: effects of attention training on target recognition and distractor salience in an auditory selection task.

Behavioral and electrophysiological measures of target and distractor processing were examined in an auditory selective attention task before and after three weeks of distractor suppression training. Behaviorally, training improved target recognition and led to less conservative and more rapid responding. Training also effectively shortened the temporal distance between distractors and targets needed to achieve a fixed level of target sensitivity. The effects of training on event-related potentials were restricted to the distracting stimulus: earlier N1 latency, enhanced P2 amplitude, and weakened P3 amplitude. Nevertheless, as distractor P2 amplitude increased, so too did target P3 amplitude, connecting experience-dependent changes in distractor processing with greater distinctiveness of targets in working memory. We consider the effects of attention training on the processing priorities, representational noise, and inhibitory processes operating in working memory.

Bio-swarm-pipeline: a light-weight, extensible batch processing system for efficient biomedical data processing.

A streamlined scientific workflow system that can track the details of the data processing history is critical for the efficient handling of fundamental routines used in scientific research. In the scientific workflow research community, the information that describes the details of data processing history is referred to as "provenance" which plays an important role in most of the existing workflow management systems. Despite its importance, however, provenance modeling and management is still a relatively new area in the scientific workflow research community. The proper scope, representation, granularity and implementation of a provenance model can vary from domain to domain and pose a number of challenges for an efficient pipeline design. This paper provides a case study on structured provenance modeling and management problems in the neuroimaging domain by introducing the Bio-Swarm-Pipeline. This new model, which is evaluated in the paper through real world scenarios, systematically addresses the provenance scope, representation, granularity, and implementation issues related to the neuroimaging domain. Although this model stems from applications in neuroimaging, the system can potentially be adapted to a wide range of bio-medical application scenarios.

P2 enhancement from auditory discrimination training is associated with improved reaction times.

This study examined the effects of training in a pure tone discrimination task on relations between behavioral performance and the magnitude of auditory event-related potentials (ERPs). Participants performed both passive (listening) and active (detecting) oddball tasks in a pretest and two posttests (1 and 9 weeks after training). Training produced a long-term benefit in both perceptual sensitivity and reaction times (RT). Training enhanced the amplitude of the P2 ERP component to both standards and deviants at both early and delayed posttests. Importantly, P2 enhancement was strongly associated with discrimination RT, suggesting that experience facilitates rapid, preattentive access to perceptual representations. Training also elevated the mismatch negativity, possibly due to the strengthening of acoustic traces. Finally, training enhanced the amplitude of the P3 component to deviants across posttests, indicating a long-lasting effect of discrimination training on stimulus salience.

Know your place: neural processing of social hierarchy in humans.

Social hierarchies guide behavior in many species, including humans, where status also has an enormous impact on motivation and health. However, little is known about the underlying neural representation of social hierarchies in humans. In the present study, we identify dissociable neural responses to perceived social rank using functional magnetic resonance imaging (fMRI) in an interactive, simulated social context. In both stable and unstable social hierarchies, viewing a superior individual differentially engaged perceptual-attentional, saliency, and cognitive systems, notably dorsolateral prefrontal cortex. In the unstable hierarchy setting, additional regions related to emotional processing (amygdala), social cognition (medial prefrontal cortex), and behavioral readiness were recruited. Furthermore, social hierarchical consequences of performance were neurally dissociable and of comparable salience to monetary reward, providing a neural basis for the high motivational value of status. Our results identify neural mechanisms that may mediate the enormous influence of social status on human behavior and health.

Behavioral and electrophysiological effects of distractor variation on auditory selective attention.

Two experiments investigated the effects on auditory selection of varying distractor values in memory. Participants performed a set of control (single distractor) and distractor-variation (multiple distractors) tasks, classifying targets by pitch (Experiments 1A and 2) or loudness (Experiment 1B) while ignoring previously presented (and spatially separate) distractors. When both targets and distractors varied in pitch, the degree of variation among the distractors increasingly disrupted classification accuracy and reaction time to the targets. Physiologically, the degree of distractor variation boosted the N1 response to distractors, the P2 response to both targets and distractors, and the slow-wave response to targets (400-600 ms after stimulus onset). The results suggest that target representations are diminished in distinctiveness as distractors activate a wider range of the task-relevant continuum in working memory.

Neural basis of first and second language processing of sentence-level linguistic prosody.

A fundamental question in multilingualism is whether the neural substrates are shared or segregated for the two or more languages spoken by polyglots. This study employs functional MRI to investigate the neural substrates underlying the perception of two sentence-level prosodic phenomena that occur in both Mandarin Chinese (L1) and English (L2): sentence focus (sentence-initial vs. -final position of contrastive stress) and sentence type (declarative vs. interrogative modality). Late-onset, medium proficiency Chinese-English bilinguals were asked to selectively attend to either sentence focus or sentence type in paired three-word sentences in both L1 and L2 and make speeded-response discrimination judgments. L1 and L2 elicited highly overlapping activations in frontal, temporal, and parietal lobes. Furthermore, region of interest analyses revealed that for both languages the sentence focus task elicited a leftward asymmetry in the supramarginal gyrus; both tasks elicited a rightward asymmetry in the mid-portion of the middle frontal gyrus. A direct comparison between L1 and L2 did not show any difference in brain activation in the sentence type task. In the sentence focus task, however, greater activation for L2 than L1 occurred in the bilateral anterior insula and superior frontal sulcus. The sentence focus task also elicited a leftward asymmetry in the posterior middle temporal gyrus for L1 only. Differential activation patterns are attributed primarily to disparities between L1 and L2 in the phonetic manifestation of sentence focus. Such phonetic divergences lead to increased computational demands for processing L2. These findings support the view that L1 and L2 are mediated by a unitary neural system despite late age of acquisition, although additional neural resources may be required in task-specific circumstances for unequal bilinguals.

Statistical analysis of morphological differences between brains.

Recent study in neuroscience has observed evidence that the anatomic structures in human brains might have certain connection with the functioning. This triggers the interest in morphological study of cortical surfaces and in comparison of different ethnic groups. This article compares the MRI brain datasets of 10 Chinese and 10 Caucasians. A statistical analysis was applied to the white matter volumes in these datasets and evaluate the dissimilarities between the two groups using various intuitive measures. This analysis has revealed systematic morphological differences between the two ethnic groups.

Activation of the left planum temporale in pitch processing is shaped by language experience.

Implicit, abstract knowledge acquired through language experience can alter cortical processing of complex auditory signals. To isolate prelexical processing of linguistic tones (i.e., pitch variations that convey part of word meaning), a novel design was used in which hybrid stimuli were created by superimposing Thai tones onto Chinese syllables (tonal chimeras) and Chinese tones onto the same syllables (Chinese words). Native speakers of tone languages (Chinese, Thai) underwent fMRI scans as they judged tones from both stimulus sets. In a comparison of native vs. non-native tones, overlapping activity was identified in the left planum temporale (PT). In this area a double dissociation between language experience and neural representation of pitch occurred such that stronger activity was elicited in response to native as compared to non-native tones. This finding suggests that cortical processing of pitch information can be shaped by language experience and, moreover, that lateralized PT activation can be driven by top-down cognitive processing.

Neural circuitry underlying sentence-level linguistic prosody.

This study investigates the neural substrates underlying the perception of two sentence-level prosodic phenomena in Mandarin Chinese: contrastive stress (initial vs. final emphasis position) and intonation (declarative vs. interrogative modality). In an fMRI experiment, Chinese and English listeners were asked to selectively attend to either stress or intonation in paired 3-word sentences, and make speeded-response discrimination judgments. Between-group comparisons revealed that the Chinese group exhibited significantly greater activity in the left supramarginal gyrus and posterior middle temporal gyrus relative to the English group for both tasks. These same two regions showed a leftward asymmetry in the stress task for the Chinese group only. For both language groups, rightward asymmetries were observed in the middle portion of the middle frontal gyrus across tasks. All task effects involved greater activity for the stress task as compared to intonation. A left-sided task effect was observed in the posterior middle temporal gyrus for the Chinese group only. Both language groups exhibited a task effect bilaterally in the intraparietal sulcus. These findings support the emerging view that speech prosody perception involves a dynamic interplay among widely distributed regions not only within a single hemisphere but also between the two hemispheres. This model of speech prosody processing emphasizes the role of right hemisphere regions for complex-sound analysis, whereas task-dependent regions in the left hemisphere predominate when language processing is required.

Neural network for encoding immediate memory in phonological processing.

The aim of this fMRI study was to identify neuroanatomical substrates of immediate memory underlying phonological processing. To distinguish encoding of immediate memory from rehearsal, participants were required to match tones from the first and last positions of a three-syllable list to their following probes in an immediate-recognition paradigm. The first position task included intervening distractors between the target and probe. Increased activations were found in the left inferior frontal gyrus, right lateral cerebellum, and medial frontal gyrus for the target tone in first position. This network mediates articulatory encoding in immediate-response, and articulatory rehearsal in delayed-response paradigms. These findings support a working memory model in which rehearsal is optional, while encoding is an obligatory component of the phonological loop.

Hemispheric roles in the perception of speech prosody.

Speech prosody is processed in neither a single region nor a specific hemisphere, but engages multiple areas comprising a large-scale spatially distributed network in both hemispheres. It remains to be elucidated whether hemispheric lateralization is based on higher-level prosodic representations or lower-level encoding of acoustic cues, or both. A cross-language (Chinese; English) fMRI study was conducted to examine brain activity elicited by selective attention to Chinese intonation (I) and tone (T) presented in three-syllable (I3, T3) and one-syllable (I1, T1) utterance pairs in a speeded response, discrimination paradigm. The Chinese group exhibited greater activity than the English in a left inferior parietal region across tasks (I1, I3, T1, T3). Only the Chinese group exhibited a leftward asymmetry in inferior parietal and posterior superior temporal (I1, I3, T1, T3), anterior temporal (I1, I3, T1, T3), and frontopolar (I1, I3) regions. Both language groups shared a rightward asymmetry in the mid portions of the superior temporal sulcus and middle frontal gyrus irrespective of prosodic unit or temporal interval. Hemispheric laterality effects enable us to distinguish brain activity associated with higher-order prosodic representations in the Chinese group from that associated with lower-level acoustic/auditory processes that are shared among listeners regardless of language experience. Lateralization is influenced by language experience that shapes the internal prosodic representation of an external auditory signal. We propose that speech prosody perception is mediated primarily by the RH, but is left-lateralized to task-dependent regions when language processing is required beyond the auditory analysis of the complex sound.

Neural correlates of segmental and tonal information in speech perception.

The Chinese language provides an optimal window for investigating both segmental and suprasegmental units. The aim of this cross-linguistic fMRI study is to elucidate neural mechanisms involved in extraction of Chinese consonants, rhymes, and tones from syllable pairs that are distinguished by only one phonetic feature (minimal) vs. those that are distinguished by two or more phonetic features (non-minimal). Triplets of Chinese monosyllables were constructed for three tasks comparing consonants, rhymes, and tones. Each triplet consisted of two target syllables with an intervening distracter. Ten Chinese and English subjects were asked to selectively attend to targeted sub-syllabic components and make same-different judgments. Direct between-group comparisons in both minimal and non-minimal pairs reveal increased activation for the Chinese group in predominantly left-sided frontal, parietal, and temporal regions. Within-group comparisons of non-minimal and minimal pairs show that frontal and parietal activity varies for each sub-syllabic component. In the frontal lobe, the Chinese group shows bilateral activation of the anterior middle frontal gyrus (MFG) for rhymes and tones only. Within-group comparisons of consonants, rhymes, and tones show that rhymes induce greater activation in the left posterior MFG for the Chinese group when compared to consonants and tones in non-minimal pairs. These findings collectively support the notion of a widely distributed cortical network underlying different aspects of phonological processing. This neural network is sensitive to the phonological structure of a listener's native language. Hum. Brain Mapping 20:185-200, 2003.

Selective attention to lexical tones recruits left dorsal frontoparietal network.

Phonological processing activates a posterior superior region of inferior prefrontal cortex, but questions still remain about the relationship between phonology and this particular region. In this fMRI experiment, subjects were asked to match an intrasyllabic unit (Chinese tones) in an experimental condition vs. whole syllables in a control condition. The only difference between conditions is mediated by focus of attention, either to a subpart (i.e. tone) of the syllable or to the whole syllable itself. Phonetic extraction of Chinese tones reveals a dorsal frontoparietal network in the LH that engages selective attention and internal guidance, two mediational components that are not restricted to phonological processing.

Temporal integration of speech prosody is shaped by language experience: an fMRI study.

Differences in hemispheric functions underlying speech perception may be related to the size of temporal integration windows over which prosodic features (e.g., pitch) span in the speech signal. Chinese tone and intonation, both signaled by variations in pitch contours, span over shorter (local) and longer (global) temporal domains, respectively. This cross-linguistic (Chinese and English) study uses functional magnetic resonance imaging to show that pitch contours associated with tones are processed in the left hemisphere by Chinese listeners only, whereas pitch contours associated with intonation are processed predominantly in the right hemisphere. These findings argue against the view that all aspects of speech prosody are lateralized to the right hemisphere, and promote the idea that varying-sized temporal integration windows reflect a neurobiological adaptation to meet the 'prosodic needs' of a particular language.

A cross-linguistic fMRI study of perception of intonation and emotion in Chinese.

Conflicting data from neurobehavioral studies of the perception of intonation (linguistic) and emotion (affective) in spoken language highlight the need to further examine how functional attributes of prosodic stimuli are related to hemispheric differences in processing capacity. Because of similarities in their acoustic profiles, intonation and emotion permit us to assess to what extent hemispheric lateralization of speech prosody depends on functional instead of acoustical properties. To examine how the brain processes linguistic and affective prosody, an fMRI study was conducted using Chinese, a tone language in which both intonation and emotion may be signaled prosodically, in addition to lexical tones. Ten Chinese and 10 English subjects were asked to perform discrimination judgments of intonation (I: statement, question) and emotion (E: happy, angry, sad) presented in semantically neutral Chinese sentences. A baseline task required passive listening to the same speech stimuli (S). In direct between-group comparisons, the Chinese group showed left-sided frontoparietal activation for both intonation (I vs. S) and emotion (E vs. S) relative to baseline. When comparing intonation relative to emotion (I vs. E), the Chinese group demonstrated prefrontal activation bilaterally; parietal activation in the left hemisphere only. The reverse comparison (E vs. I), on the other hand, revealed that activation occurred in anterior and posterior prefrontal regions of the right hemisphere only. These findings show that some aspects of perceptual processing of emotion are dissociable from intonation, and, moreover, that they are mediated by the right hemisphere.

A cross-linguistic FMRI study of spectral and temporal cues underlying phonological processing.

It remains a matter of controversy precisely what kind of neural mechanisms underlie functional asymmetries in speech processing. Whereas some studies support speech-specific circuits, others suggest that lateralization is dictated by relative computational demands of complex auditory signals in the spectral or time domains. To examine how the brain processes linguistically relevant spectral and temporal information, a functional magnetic resonance imaging study was conducted using Thai speech, in which spectral processing associated with lexical tones and temporal processing associated with vowel length can be differentiated. Ten Thai and 10 Chinese subjects were asked to perform discrimination judgments of pitch and timing patterns presented in the same auditory stimuli under two different conditions: speech (Thai) and nonspeech (hums). In the speech condition, tasks required judging Thai tones (T) and vowel length (VL); in the nonspeech condition, homologous pitch contours (P) and duration patterns (D). A remaining task required listening passively to nonspeech hums (L). Only the Thai group showed activation in the left inferior prefrontal cortex in speech minus nonspeech contrasts for spectral (T vs. P) and temporal (VL vs. D) cues. Thai and Chinese groups, however, exhibited similar fronto-parietal activation patterns in nonspeech hums minus passive listening contrasts for spectral (P vs. L) and temporal (D vs. L) cues. It appears that lower level specialization for acoustic cues in the spectral and temporal domains cannot be generalized to abstract higher order levels of phonological processing. Regardless of the neural mechanisms underlying low-level auditory processing, our findings clearly indicate that hemispheric specialization is sensitive to language-specific factors.

Neural circuitry underlying perception of duration depends on language experience.

Thai, a language which exhibits a phonemic opposition in vowel length, allows us to compare temporal patterns in linguistic and nonlinguistic contexts. Functional MRI data were collected from Thai and English subjects in a speeded-response, selective attention paradigm as they performed same/different judgments of vowel duration and consonants (Thai speech) and hum duration (nonspeech). Activation occurred predominantly in left inferior prefrontal cortex in both speech tasks for the Thai group, but only in the consonant task for the English group. The Thai group exhibited activation in the left mid superior temporal gyrus in both speech tasks; the English group in the posterior superior temporal gyrus bilaterally. In the hum duration task, peak activation was observed bilaterally in prefrontal cortex for both groups. These crosslinguistic data demonstrate that encoding of complex auditory signals is influenced by their functional role in a particular language.