Joint Multi-modal Parcellation of the Human Striatum: Functions and Clinical Relevance.

The human striatum is essential for both low- and high-level functions and has been implicated in the pathophysiology of various prevalent disorders, including Parkinson's disease (PD) and schizophrenia (SCZ). It is known to consist of structurally and functionally divergent subdivisions. However, previous parcellations are based on a single neuroimaging modality, leaving the extent of the multi-modal organization of the striatum unknown. Here, we investigated the organization of the striatum across three modalities-resting-state functional connectivity, probabilistic diffusion tractography, and structural covariance-to provide a holistic convergent view of its structure and function. We found convergent clusters in the dorsal, dorsolateral, rostral, ventral, and caudal striatum. Functional characterization revealed the anterior striatum to be mainly associated with cognitive and emotional functions, while the caudal striatum was related to action execution. Interestingly, significant structural atrophy in the rostral and ventral striatum was common to both PD and SCZ, but atrophy in the dorsolateral striatum was specifically attributable to PD. Our study revealed a cross-modal convergent organization of the striatum, representing a fundamental topographical model that can be useful for investigating structural and functional variability in aging and in clinical conditions.

Functional differentiation in the human ventromedial frontal lobe: A data-driven parcellation.

Ventromedial regions of the frontal lobe (vmFL) are thought to play a key role in decision-making and emotional regulation. However, aspects of this area's functional organization, including the presence of a multiple subregions, their functional and anatomical connectivity, and the cross-species homologies of these subregions with those of other species, remain poorly understood. To address this uncertainty, we employed a two-stage parcellation of the region to identify six distinct structures within the region on the basis of data-driven classification of functional connectivity patterns obtained using the meta-analytic connectivity modeling (MACM) approach. From anterior to posterior, the derived subregions included two lateralized posterior regions, an intermediate posterior region, a dorsal and ventral central region, and a single anterior region. The regions were characterized further by functional connectivity derived using resting-state fMRI and functional decoding using the Brain Map database. In general, the regions could be differentiated on the basis of different patterns of functional connectivity with canonical "default mode network" regions and/or subcortical regions such as the striatum. Together, the findings suggest the presence of functionally distinct neural structures within vmFL, consistent with data from experimental animals as well prior demonstrations of anatomical differences within the region. Detailed correspondence with the anterior cingulate, medial orbitofrontal cortex, and rostroventral prefrontal cortex, as well as specific animal homologs are discussed. The findings may suggest future directions for resolving potential functional and structural correspondence of subregions within the frontal lobe across behavioral contexts, and across mammalian species.

Convergent neural representations of experimentally-induced acute pain in healthy volunteers: A large-scale fMRI meta-analysis.

Characterizing a reliable, pain-related neural signature is critical for translational applications. Many prior fMRI studies have examined acute nociceptive pain-related brain activation in healthy participants. However, synthesizing these data to identify convergent patterns of activation can be challenging due to the heterogeneity of experimental designs and samples. To address this challenge, we conducted a comprehensive meta-analysis of fMRI studies of stimulus-induced pain in healthy participants. Following pre-registration, two independent reviewers evaluated 4,927 abstracts returned from a search of 8 databases, with 222 fMRI experiments meeting inclusion criteria. We analyzed these experiments using Activation Likelihood Estimation with rigorous type I error control (voxel height p < 0.001, cluster p < 0.05 FWE-corrected) and found a convergent, largely bilateral pattern of pain-related activation in the secondary somatosensory cortex, insula, midcingulate cortex, and thalamus. Notably, these regions were consistently recruited regardless of stimulation technique, location of induction, and participant sex. These findings suggest a highly-conserved core set of pain-related brain areas, encouraging applications as a biomarker for novel therapeutics targeting acute nociceptive pain.

Brain dynamics and connectivity networks under natural auditory stimulation.

The analysis of functional magnetic resonance imaging (fMRI) data is challenging when subjects are under exposure to natural sensory stimulation. In this study, a two-stage approach was developed to enable the identification of connectivity networks involved in the processing of information in the brain under natural sensory stimulation. In the first stage, the degree of concordance between the results of inter-subject and intra-subject correlation analyses is assessed statistically. The microstructurally (i.e., cytoarchitectonically) defined brain areas are designated either as concordant in which the results of both correlation analyses are in agreement, or as discordant in which one analysis method shows a higher proportion of supra-threshold voxels than does the other. In the second stage, connectivity networks are identified using the time courses of supra-threshold voxels in brain areas contingent upon the classifications derived in the first stage. In an empirical study, fMRI data were collected from 40 young adults (19 males, average age 22.76 ±â€¯3.25), who underwent auditory stimulation involving sound clips of human voices and animal vocalizations under two operational conditions (i.e., eyes-closed and eyes-open). The operational conditions were designed to assess confounding effects due to auditory instructions or visual perception. The proposed two-stage analysis demonstrated that stress modulation (affective) and language networks in the limbic and cortical structures were respectively engaged during sound stimulation, and presented considerable variability among subjects. The network involved in regulating visuomotor control was sensitive to the eyes-open instruction, and presented only small variations among subjects. A high degree of concordance was observed between the two analyses in the primary auditory cortex which was highly sensitive to the pitch of sound clips. Our results have indicated that brain areas can be identified as concordant or discordant based on the two correlation analyses. This may further facilitate the search for connectivity networks involved in the processing of information under natural sensory stimulation.

Functional brain alterations in acute sleep deprivation: An activation likelihood estimation meta-analysis.

Sleep deprivation (SD) is a common problem in modern societies, which leads to cognitive dysfunctions including attention lapses, impaired working memory, hindering decision making, impaired emotional processing, and motor vehicle accidents. Numerous neuroimaging studies have investigated the neural correlates of SD, but these studies have reported inconsistent results. Thus, we aimed to identify convergent patterns of abnormal brain functions due to acute SD. Based on the preferred reporting for systematic reviews and meta-analyses statement, we searched the PubMed database and performed reference tracking and finally retrieved 31 eligible functional neuroimaging studies. Then, we applied activation estimation likelihood meta-analysis and found reduced activity mainly in the right intraparietal sulcus and superior parietal lobule. The functional decoding analysis using the BrainMap database indicated that this region is mostly related to visuospatial perception, memory and reasoning. The significant co-activation of this region using the BrainMap database were found in the left superior parietal lobule, intraparietal sulcus, bilateral occipital cortex, left fusiform gyrus and thalamus. This region also connected with the superior parietal lobule, intraparietal sulcus, insula, inferior frontal gyrus, precentral, occipital and cerebellum through resting-state functional connectivity in healthy subjects. Taken together, our findings highlight the role of superior parietal cortex in SD.

Neural correlates of action: Comparing meta-analyses of imagery, observation, and execution.

Several models propose Motor Imagery, Action Observation, and Movement Execution recruit the same brain regions. There is, however, no quantitative synthesis of the literature that directly compares their respective networks. Here we summarized data from neuroimaging experiments examining Motor Imagery (303 experiments, 4902 participants), Action Observation (595 experiments, 11,032 participants), and related control tasks involving Movement Execution (142 experiments, 2302 participants). Comparisons across these networks showed that Motor Imagery and Action Observation recruited similar premotor-parietal cortical networks. However, while Motor Imagery recruited a similar subcortical network to Movement Execution, Action Observation did not consistently recruit any subcortical areas. These data quantify and amend previous models of the similarities in the networks for Motor Imagery, Action Observation, and Movement Execution, while highlighting key differences in their recruitment of motor cortex, parietal cortex, and subcortical structures.

Modulation of affective face processing deficits in Schizophrenia by congruent emotional sounds.

Schizophrenia is a psychiatric disorder resulting in prominent impairments in social functioning. Thus, clinical research has focused on underlying deficits of emotion processing and their linkage to specific symptoms and neurobiological dysfunctions. Although there is substantial research investigating impairments in unimodal affect recognition, studies in schizophrenia exploring crossmodal emotion processing are rare. Therefore, event-related potentials were measured in 15 patients with schizophrenia and 15 healthy controls while rating the expression of happy, fearful and neutral faces and concurrently being distracted by emotional or neutral sounds. Compared with controls, patients with schizophrenia revealed significantly decreased P1 and increased P2 amplitudes in response to all faces, independent of emotion or concurrent sound. Analyzing these effects with regard to audiovisual (in)congruence revealed that P1 amplitudes in patients were only reduced in response to emotionally incongruent stimulus pairs, whereas similar amplitudes between groups could be observed for congruent conditions. Correlation analyses revealed a significant negative correlation between general symptom severity (Brief Psychiatric Rating Scale-V4) and P1 amplitudes in response to congruent audiovisual stimulus pairs. These results indicate that early visual processing deficits in schizophrenia are apparent during emotion processing but, depending on symptom severity, these deficits can be restored by presenting concurrent emotionally congruent sounds.

Crossmodal emotional integration in major depression.

Major depression goes along with affective and social-cognitive deficits. Most research on affective deficits in depression has, however, only focused on unimodal emotion processing, whereas in daily life, emotional perception is often highly dependent on the evaluation of multimodal inputs. We thus investigated emotional audiovisual integration in patients with depression and healthy subjects. Subjects rated the expression of happy, neutral and fearful faces while concurrently being exposed to emotional or neutral sounds. Results demonstrated group differences in left inferior frontal gyrus and inferior parietal cortex when comparing incongruent to congruent happy facial conditions, mainly due to a failure of patients to deactivate these regions in response to congruent stimulus pairs. Moreover, healthy subjects decreased activation in right posterior superior temporal gyrus/sulcus and midcingulate cortex when an emotional stimulus was paired with a neutral rather than another emotional one. In contrast, patients did not show such deactivation when neutral stimuli were integrated. These results demonstrate aberrant neural response in audiovisual processing in depression, indicated by failure to deactivate regions involved in inhibition and salience processing when congruent and neutral audiovisual stimuli pairs are integrated, providing a possible mechanism of constant arousal and readiness to act in this patient group.

Mapping repetition suppression of the P50 evoked response to the human cerebral cortex.

OBJECTIVE: The cerebral network subserving repetition suppression (RS) of the P50 auditory evoked response as observed using paired-identical-stimulus (S1-S2) paradigms is not well-described. METHODS: We analyzed S1-S2 data from electrodes placed on the cortices of 64 epilepsy patients. We identified regions with maximal amplitude responses to S1 (i.e., stimulus registration), regions with maximal suppression of responses to S2 relative to S1 (i.e., RS), and regions with no or minimal RS 30-80 ms post stimulation. RESULTS: Several temporal, parietal and cingulate area regions were shown to have significant initial registration activity (i.e., strong P50 response to S1). Moreover, prefrontal, cingulate, and parietal lobe regions not previously proposed to be part of the P50 habituation neural circuitry were found to exhibit significant RS. CONCLUSIONS: The data suggest that the neural network underlying the initial phases of the RS process may include regions not previously thought to be involved like the parietal and cingulate cortexes. In addition, a significant role for the frontal lobe in mediating this function is supported. SIGNIFICANCE: A number of regions of interest are identified through invasive recording that will allow further probing of the RS function using less invasive technology.

A coordinate-based meta-analytic model of trauma processing in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) has a well-defined set of symptoms that can be elicited during traumatic imagery tasks. For this reason, trauma imagery tasks are often employed in functional neuroimaging studies. Here, coordinate-based meta-analysis (CBM) was used to pool eight studies applying traumatic imagery tasks to identify sites of task-induced activation in 170 PTSD patients and 104 healthy controls. In this way, right anterior cingulate (ACC), right posterior cingulate (PCC), and left precuneus (Pcun) were identified as regions uniquely active in PTSD patients relative to healthy controls. To further characterize these regions, their normal interactions, and their typical functional roles, meta-analytic connectivity modeling (MACM) with behavioral filtering was applied. MACM indicated that the PCC and Pcun regions were frequently co-active and associated with processing of cognitive information, particularly in explicit memory tasks. Emotional processing was particularly associated with co-activity of the ACC and PCC, as mediated by the thalamus. By narrowing the regions of interest to those commonly active across multiple studies (using CBM) and developing a priori hypotheses about directed probabilistic dependencies amongst these regions, this proposed model-when applied in the context of graphical and causal modeling-should improve model fit and thereby increase statistical power for detecting differences between subject groups and between treatments in neuroimaging studies of PTSD.

Staying responsive to the world: modality-specific and -nonspecific contributions to speeded auditory, tactile, and visual stimulus detection.

Sustained responsiveness to external stimulation is fundamental to many time-critical interactions with the outside world. We used functional magnetic resonance imaging during speeded stimulus detection to identify convergent and divergent neural correlates of maintaining the readiness to respond to auditory, tactile, and visual stimuli. In addition, using a multimodal condition, we investigated the effect of making stimulus modality unpredictable. Relative to sensorimotor control tasks, all three unimodal detection tasks elicited stronger activity in the right temporo-parietal junction, inferior frontal cortex, anterior insula, dorsal premotor cortex, and anterior cingulate cortex as well as bilateral mid-cingulum, midbrain, brainstem, and medial cerebellum. The multimodal detection condition additionally activated left dorsal premotor cortex and bilateral precuneus. Modality-specific modulations were confined to respective sensory areas: we found activity increases in relevant, and decreases in irrelevant sensory cortices. Our findings corroborate the modality independence of a predominantly right-lateralized core network for maintaining an alert (i.e., highly responsive) state and extend previous results to the somatosensory modality. Monitoring multiple sensory channels appears to induce additional processing, possibly related to stimulus-driven shifts of intermodal attention. The results further suggest that directing attention to a given sensory modality selectively enhances and suppresses sensory processing-even in simple detection tasks, which do not require inter- or intra-modal selection.

Incongruence effects in crossmodal emotional integration.

Emotions are often encountered in a multimodal fashion. Consequently, contextual framing by other modalities can alter the way that an emotional facial expression is perceived and lead to emotional conflict. Whole brain fMRI data was collected when 35 healthy subjects judged emotional expressions in faces while concurrently being exposed to emotional (scream, laughter) or neutral (yawning) sounds. The behavioral results showed that subjects rated fearful and neutral faces as being more fearful when accompanied by screams than compared to yawns (and laughs for fearful faces). Moreover, the imaging data revealed that incongruence of emotional valence between faces and sounds led to increased activation in the middle cingulate cortex, right superior frontal cortex, right supplementary motor area as well as the right temporoparietal junction. Against expectations no incongruence effects could be found in the amygdala. Further analyses revealed that, independent of emotional valence congruency, the left amygdala was consistently activated when the information from both modalities was emotional. If a neutral stimulus was present in one modality and emotional in the other, activation in the left amygdala was significantly attenuated. These results indicate that incongruence of emotional valence in audiovisual integration activates a cingulate-fronto-parietal network involved in conflict monitoring and resolution. Furthermore in audiovisual pairing amygdala responses seem to signal also the absence of any neutral feature rather than only the presence of an emotionally charged one.

Modality-independent involvement of the left BA 44 during lexical decision making.

During a lexical decision task, lexical decision making can be distinguished from lexical retrieval. Lexical decision making is independent of stimulus modality and not reflected in the decision times, whereas the opposite holds for lexical retrieval. In neuroimaging studies investigating lexical decision tasks with either visual or auditory stimuli these two processes have so far been confused. Therefore, it is not clear whether the activation of Broca's region, consisting of the left Brodmann's area (BA) 44 and BA 45, reported in such studies really reflects lexical decision making. The present event-related fMRI study investigated the role of Broca's region in lexical decision by analyzing brain activation that is independent of stimulus modality or decision times. Twenty-two healthy participants performed lexical decisions on visual and auditory real words and pseudo-words. The left BA 44 was conjointly activated during visual and auditory lexical decisions as compared to rest indicating the modality-independent involvement of BA 44 in lexical decision tasks in general. To identify brain activation related to lexical decision making rather than lexical retrieval the decision times were entered as covariates into the fMRI analysis. In this analysis, the left BA 44 was activated for visual and for auditory lexical decision making. These results indicate that the left BA 44 as a distinct sub-part of Broca's region plays an important role in lexical decision making independently of stimulus modality and decision times.

Response properties of human amygdala subregions: evidence based on functional MRI combined with probabilistic anatomical maps.

The human amygdala is thought to play a pivotal role in the processing of emotionally significant sensory information. The major subdivisions of the human amygdala-the laterobasal group (LB), the superficial group (SF), and the centromedial group (CM)-have been anatomically delineated, but the functional response properties of these amygdala subregions in humans are still unclear. We combined functional MRI with cyto-architectonically defined probabilistic maps to analyze the response characteristics of amygdala subregions in subjects presented with auditory stimuli. We found positive auditory stimulation-related signal changes predominantly in probabilistically defined LB, and negative responses predominantly in SF and CM. In the left amygdala, mean response magnitude in the core area of LB with 90-100% assignment probability was significantly larger than in the core areas of SF and CM. These differences were observed for pleasant and unpleasant stimuli. Our findings reveal that the probabilistically defined anatomical subregions of the human amygdala show distinctive fMRI response patterns. The stronger auditory responses in LB as compared with SF and CM may reflect a predominance of auditory inputs to human LB, similar to many animal species in which the majority of sensory, including auditory, afferents project to this subdivision of the amygdala. Our study indicates that the intrinsic functional differentiation of the human amygdala may be probed using fMRI combined with probabilistic anatomical maps.