Many speech sounds and animal vocalizations contain components, referred to as complex tones, that consist of a fundamental frequency (F0) and higher harmonics. In this study we examined single-unit activity recorded in the core (A1) and lateral belt (LB) areas of auditory cortex in two rhesus monkeys as they listened to pure tones and pitch-shifted conspecific vocalizations ("coos"). The latter consisted of complex-tone segments in which F0 was matched to a corresponding pure-tone stimulus. In both animals, neuronal latencies to pure-tone stimuli at the best frequency (BF) were ~10 to 15 ms longer in LB than in A1. This might be expected, since LB is considered to be at a hierarchically higher level than A1. On the other hand, the latency of LB responses to coos was ~10 to 20 ms shorter than to the corresponding pure-tone BF, suggesting facilitation in LB by the harmonics. This latency reduction by coos was not observed in A1, resulting in similar coo latencies in A1 and LB. Multi-peaked neurons were present in both A1 and LB; however, harmonically-related peaks were observed in LB for both early and late response components, whereas in A1 they were observed only for late components. Our results suggest that harmonic features, such as relationships between specific frequency intervals of communication calls, are processed at relatively early stages of the auditory cortical pathway, but preferentially in LB.

Crossmodal associations form a fundamental aspect of our daily lives. In this study we investigated the neural correlates of crossmodal association in early sensory cortices using magnetoencephalography (MEG). We used a paired associate recognition paradigm in which subjects were tested after multiple training sessions over a span of four weeks. Subjects had to learn 12 abstract, nonlinguistic, pairs of auditory and visual objects that consisted of crossmodal (visual-auditory, VA; auditory-visual, AV) and unimodal (visual-visual, VV; auditory-auditory, AA) paired items. Visual objects included abstract, non-nameable, fractal-like images, and auditory objects included abstract tone sequences. During scanning, subjects were shown the first item of a pair (S1), followed by a delay, then the simultaneous presentation of a visual and auditory stimulus (S2). Subjects were instructed to indicate whether either of the S2 stimuli contained the correct paired associate of S1. Synthetic aperture magnetometry (SAMspm), a minimum variance beamformer, was then used to assess source power differences between the crossmodal conditions and their corresponding unimodal conditions (i.e., AV-AA and VA-VV) in the beta (15-30 Hz) and low gamma frequencies (31-54 Hz) during the S1 period. We found greater power during S1 in the corresponding modality-specific association areas for crossmodal compared with unimodal stimuli. Thus, even in the absence of explicit sensory input, the retrieval of well-learned, crossmodal pairs activate sensory areas associated with the corresponding modality. These findings support theories which posit that modality-specific regions of cortex are involved in the storage and retrieval of sensory-specific items from long-term memory.

Manual gestures occur on a continuum from co-speech gesticulations to conventionalized emblems to language signs. Our goal in the present study was to understand the neural bases of the processing of gestures along such a continuum. We studied four types of gestures, varying along linguistic and semantic dimensions: linguistic and meaningful American Sign Language (ASL), non-meaningful pseudo-ASL, meaningful emblematic, and nonlinguistic, non-meaningful made-up gestures. Pre-lingually deaf, native signers of ASL participated in the fMRI study and performed two tasks while viewing videos of the gestures: a visuo-spatial (identity) discrimination task and a category discrimination task. We found that the categorization task activated left ventral middle and inferior frontal gyrus, among other regions, to a greater extent compared to the visual discrimination task, supporting the idea of semantic-level processing of the gestures. The reverse contrast resulted in enhanced activity of bilateral intraparietal sulcus, supporting the idea of featural-level processing (analogous to phonological-level processing of speech sounds) of the gestures. Regardless of the task, we found that brain activation patterns for the nonlinguistic, non-meaningful gestures were the most different compared to the ASL gestures. The activation patterns for the emblems were most similar to those of the ASL gestures and those of the pseudo-ASL were most similar to the nonlinguistic, non-meaningful gestures. The fMRI results provide partial support for the conceptualization of different gestures as belonging to a continuum and the variance in the fMRI results was best explained by differences in the processing of gestures along the semantic dimension.

Broca's area in the inferior frontal gyrus consists of two cytoarchitectonically defined regions-Brodmann areas (BA) 44 and 45. Combining probabilistic maps of these two areas with functional neuroimaging data obtained using PET, it is shown that BA45, not BA44, is activated by both speech and signing during the production of language narratives in bilingual subjects fluent from early childhood in both American Sign Language (ASL) and English when the generation of complex movements and sounds is taken into account. It is BA44, not BA45, that is activated by the generation of complex articulatory movements of oral/laryngeal or limb musculature. The same patterns of activation are found for oral language production in a group of English speaking monolingual subjects. These findings implicate BA45 as the part of Broca's area that is fundamental to the modality-independent aspects of language generation.

Subjective tinnitus is the perception of sound in the absence of an external source. Tinnitus is often accompanied by hearing loss but not everyone with hearing loss experiences tinnitus. We examined neuroanatomical alterations associated with hearing loss and tinnitus in three groups of subjects: those with hearing loss with tinnitus, those with hearing loss without tinnitus and normal hearing controls without tinnitus. To examine changes in gray matter we used structural MRI scans and voxel-based morphometry (VBM) and to identify changes in white matter tract orientation we used diffusion tensor imaging (DTI). A major finding of our study was that there were both gray and white matter changes in the vicinity of the auditory cortex for subjects with hearing loss alone relative to those with tinnitus and those with normal hearing. We did not find significant changes in gray or white matter in subjects with tinnitus and hearing loss compared to normal hearing controls. VBM analysis revealed that individuals with hearing loss without tinnitus had gray matter decreases in anterior cingulate and superior and medial frontal gyri relative to those with hearing loss and tinnitus. Region-of-interest analysis revealed additional decreases in superior temporal gyrus for the hearing loss group compared to the tinnitus group. Investigating effects of hearing loss alone, we found gray matter decreases in superior and medial frontal gyri in participants with hearing loss compared to normal hearing controls. DTI analysis showed decreases in fractional anisotropy values in the right superior and inferior longitudinal fasciculi, corticospinal tract, inferior fronto-occipital tract, superior occipital fasciculus, and anterior thalamic radiation for the hearing loss group relative to normal hearing controls. In attempting to dissociate the effect of tinnitus from hearing loss, we observed that hearing loss rather than tinnitus had the greatest influence on gray and white matter alterations.

Categorization is fundamental to our perception and understanding of the environment. However, little is known about the neural bases underlying the categorization of sounds. Using human functional magnetic resonance imaging (fMRI) we compared the brain responses to a category discrimination task with an auditory discrimination task using identical sets of sounds. Our stimuli differed along two dimensions: a speech-nonspeech dimension and a fast-slow temporal dynamics dimension. All stimuli activated regions in the primary and nonprimary auditory cortices in the temporal cortex and in the parietal and frontal cortices for the two tasks. When comparing the activation patterns for the category discrimination task to those for the auditory discrimination task, the results show that a core group of regions beyond the auditory cortices, including inferior and middle frontal gyri, dorsomedial frontal gyrus, and intraparietal sulcus, were preferentially activated for familiar speech categories and for novel nonspeech categories. These regions have been shown to play a role in working memory tasks by a number of studies. Additionally, the categorization of nonspeech sounds activated left middle frontal gyrus and right parietal cortex to a greater extent than did the categorization of speech sounds. Processing the temporal aspects of the stimuli had a greater impact on the left lateralization of the categorization network than did other factors, particularly in the inferior frontal gyrus, suggesting that there is no inherent left hemisphere advantage in the categorical processing of speech stimuli, or for the categorization task itself.

Neuro-electromagnetic recording techniques (EEG, MEG, iEEG) provide high temporal resolution data to study the dynamics of neurocognitive networks: large scale neural assemblies involved in task-specific information processing. How does a neurocognitive network reorganize spatiotemporally on the order of a few milliseconds to process specific aspects of the task? At what times do networks segregate for task processing, and at what time scales does integration of information occur via changes in functional connectivity? Here, we propose a data analysis framework-Temporal microstructure of cortical networks (TMCN)-that answers these questions for EEG/MEG recordings in the signal space. Method validation is established on simulated MEG data from a delayed-match to-sample (DMS) task. We then provide an example application on MEG recordings during a paired associate task (modified from the simpler DMS paradigm) designed to study modality specific long term memory recall. Our analysis identified the times at which network segregation occurs for processing the memory recall of an auditory object paired to a visual stimulus (visual-auditory) in comparison to an analogous visual-visual pair. Across all subjects, onset times for first network divergence appeared within a range of 0.08-0.47 s after initial visual stimulus onset. This indicates that visual-visual and visual auditory memory recollection involves equivalent network components without any additional recruitment during an initial period of the sensory processing stage which is then followed by recruitment of additional network components for modality specific memory recollection. Therefore, we propose TMCN as a viable computational tool for extracting network timing in various cognitive tasks.

In the past few years, several studies have been directed to understanding the complexity of functional interactions between different brain regions during various human behaviors. Among these, neuroimaging research installed the notion that speech and language require an orchestration of brain regions for comprehension, planning, and integration of a heard sound with a spoken word. However, these studies have been largely limited to mapping the neural correlates of separate speech elements and examining distinct cortical or subcortical circuits involved in different aspects of speech control. As a result, the complexity of the brain network machinery controlling speech and language remained largely unknown. Using graph theoretical analysis of functional MRI (fMRI) data in healthy subjects, we quantified the large-scale speech network topology by constructing functional brain networks of increasing hierarchy from the resting state to motor output of meaningless syllables to complex production of real-life speech as well as compared to non-speech-related sequential finger tapping and pure tone discrimination networks. We identified a segregated network of highly connected local neural communities (hubs) in the primary sensorimotor and parietal regions, which formed a commonly shared core hub network across the examined conditions, with the left area 4p playing an important role in speech network organization. These sensorimotor core hubs exhibited features of flexible hubs based on their participation in several functional domains across different networks and ability to adaptively switch long-range functional connectivity depending on task content, resulting in a distinct community structure of each examined network. Specifically, compared to other tasks, speech production was characterized by the formation of six distinct neural communities with specialized recruitment of the prefrontal cortex, insula, putamen, and thalamus, which collectively forged the formation of the functional speech connectome. In addition, the observed capacity of the primary sensorimotor cortex to exhibit operational heterogeneity challenged the established concept of unimodality of this region.

Previously, a standard theory of systems level memory consolidation was developed to describe how memory recall becomes independent of the medial temporal memory system. More recently, an extended consolidation theory was proposed that predicts seven changes in regional neural activity and inter-regional functional connectivity. Using longitudinal event-related functional magnetic resonance imaging of an associate memory task, we simultaneously tested all predictions and additionally tested for consolidation-related changes in recall of associate memories at a sub-trial temporal resolution, analyzing cue, delay and target periods of each trial separately. Results consistent with the theoretical predictions were observed though two inconsistent results were also obtained. In particular, while medial temporal recall related delay period activity decreased with consolidation as predicted, visual cue activity increased for consolidated memories. Though the extended theory of memory consolidation is largely supported by our study, these results suggest that the extended theory needs further refinement and the medial temporal memory system has multiple, temporally distinct roles in associate memory recall. Neuroimaging analysis at a sub-trial temporal resolution, as used here, may further clarify the role of the hippocampal complex in memory consolidation.

Previous work using transcranial magnetic stimulation (TMS) demonstrated that the right presupplementary motor area (preSMA), a node in the fronto-basal-ganglia network, is critical for response inhibition. However, TMS influences interconnected regions, raising the possibility of a link between the preSMA activity and the functional connectivity within the network. To understand this relationship, we applied single-pulse TMS to the right preSMA during functional magnetic resonance imaging when the subjects were at rest to examine changes in neural activity and functional connectivity within the network in relation to the efficiency of response inhibition evaluated with a stop-signal task. The results showed that preSMA-TMS increased activation in the right inferior-frontal cortex (rIFC) and basal ganglia and modulated their task-free functional connectivity. Both the TMS-induced changes in the basal-ganglia activation and the functional connectivity between rIFC and left striatum, and of the overall network correlated with the efficiency of response inhibition and with the white-matter microstructure along the preSMA-rIFC pathway. These results suggest that the task-free functional and structural connectivity between the rIFCop and basal ganglia are critical to the efficiency of response inhibition. Hum Brain Mapp 37:3236-3249, 2016. © 2016 Wiley Periodicals, Inc.

Emblems are meaningful, culturally-specific hand gestures that are analogous to words. In this fMRI study, we contrasted the processing of emblematic gestures with meaningless gestures by pre-lingually Deaf and hearing participants. Deaf participants, who used American Sign Language, activated bilateral auditory processing and associative areas in the temporal cortex to a greater extent than the hearing participants while processing both types of gestures relative to rest. The hearing non-signers activated a diverse set of regions, including those implicated in the mirror neuron system, such as premotor cortex (BA 6) and inferior parietal lobule (BA 40) for the same contrast. Further, when contrasting the processing of meaningful to meaningless gestures (both relative to rest), the Deaf participants, but not the hearing, showed greater response in the left angular and supramarginal gyri, regions that play important roles in linguistic processing. These results suggest that whereas the signers interpreted emblems to be comparable to words, the non-signers treated emblems as similar to pictorial descriptions of the world and engaged the mirror neuron system.

Studies using positron emission tomography (PET) have reported that global and regional values for cerebral blood flow and metabolic rates for glucose (CMRglc and rCMRglc) decline with age in humans. We wished to determine if such decreases could have reflected a partial volume effect (PVE) of cerebral atrophy in the elderly, rather than "intrinsic" reductions per gram brain. We used PET to compare rCMRglc, before and after correcting for the PVE, between 13 healthy older men (aged: 55-82 years) and 11 healthy young men (aged: 22-34 years). PET was performed with 18F-fluoro-2-deoxy-d-glucose while the subjects were in the "resting" state (eyes covered and ears plugged with cotton). The PET scans were normalized to a common brain volume after superimposing them on the subjects' tissue segmented magnetic resonance scans. Analysis showed that rCMRglc in the absence of a PVE correction was significantly less in the older group in insular, frontal, superior temporal cortical, and thalamic regions. Statistical significant differences in rCMRglc, however, were absent after the PVE correction. Thus, statistically significant age reductions in regional brain glucose metabolism, corrected for brain atrophy, are not detectable in healthy normotensive men scanned while in the resting state.