Neural circuits and functional organization of the striatum

The basal ganglia and motor thalamic nuclei are functionally and anatomically divided into the sensorimotor, supplementary motor, premotor, associative and limbic territories. There exist both primary segregated basal ganglia-thalamocortical loops and convergence of functionally related information from different cortical areas onto these cortical basal gaglia-thalamocortical loops. The basal ganglia-thalamocortical loop arising from the sensorimotor area, supplementary motor area (SMA), premotor area and cingulate motor area provides distinct segregated subloops through the functionally distict stritial, pallidal and thalamic regions with partial overlap. The subthalamic nucleus (STN) is also topographically organized. The ventrolateral part of the caudal 2/3 levels of the medial pallidal segment (GPi) projects to the primary motor area via the oral part of the ventral lateral thalamic nucleus (VLo) (Voa, Vop by Hassler's nomenclature). The thalamic relay nuclei of the GPi projection to SMA are identified in the transitional zoe of the VApc (parvicellular part of the anterior ventral nucleus)-VLo and in the rostromedical part of the VLo. The thalamic nuclei relaying the cingulate subloop are not yet clearly defined. The supplementary motor subloop appears to be divided into the pre-SMA and SMA proper subloops. The premotor area is also divided into the dorsal premotor area subloop and the ventral premotor area subloop. It is suggested that the limbic loop consists of a number of subloops in the monkey as indicated by Haber et al. [67] and in rats [64]. We review here the microcircuitry of the striatum, as well as the convergence and integration between the functionally segregated loops. Finally, we discuss the functional implications of stritial connections.

     

Functional Connectivity Differences of the Subthalamic Nucleus Related to Parkinson's Disease

A typical feature of Parkinson's disease (PD) is pathological activity in the subthalamic nucleus (STN). Here, we tested whether in patients with PD under dopaminergic treatment functional connectivity of the STN differs from healthy controls (HC) and whether some brain regions show (anti‐) correlations between functional connectivity with STN and motor symptoms. We used functional magnetic resonance imaging to investigate whole‐brain resting‐state functional connectivity with STN in 54 patients with PD and 55 HC matched for age, gender, and within‐scanner motion. Compared to HC, we found attenuated negative STN‐coupling with Crus I of the right cerebellum and with right ventromedial prefrontal regions in patients with PD. Furthermore, we observed enhanced negative STN‐coupling with bilateral intraparietal sulcus/superior parietal cortex, right sensorimotor, right premotor, and left visual cortex compared to HC. Finally, we found a decline in positive STN‐coupling with the left insula related to severity of motor symptoms and a decline of inter‐hemispheric functional connectivity between left and right STN with progression of PD‐related motor symptoms. Motor symptom related uncoupling of the insula, a key region in the saliency network and for executive function, from the STN might be associated with well‐known executive dysfunction in PD. Moreover, uncoupling between insula and STN might also induce an insufficient setting of thresholds for the discrimination between relevant and irrelevant salient environmental stimuli, explaining observations of disturbed response control in PD. In sum, motor symptoms in PD are associated with a reduced coupling between STN and a key region for executive function. Hum Brain Mapp 37:1235–1253, 2016. © 2015 Wiley Periodicals, Inc .     

Information processing from the motor cortices to the subthalamic nucleus and globus pallidus and their somatotopic organizations revealed electrophysiologically in monkeys

To understand how the information derived from different motor cortical areas representing different body parts is organized in the basal ganglia, we examined the neuronal responses in the subthalamic nucleus (STN), and the external (GPe) and internal (GPi) segments of the globus pallidus (input, relay and output nuclei, respectively) to stimulation of the orofacial, forelimb and hindlimb regions of the primary motor cortex (MI) and supplementary motor area (SMA) in macaque monkeys under the awake state. Most STN and GPe/GPi neurons responded exclusively to stimulation of either the MI or SMA, and one‐fourth to one‐third of neurons responded to both. STN neurons responding to the hindlimb, forelimb and orofacial regions of the MI were located along the medial–lateral axis in the posterolateral STN, while neurons responding to the orofacial region of the SMA were located more medially than the others in the anteromedial STN. GPe/GPi neurons responding to the hindlimb, forelimb and orofacial regions of the MI were found along the dorsal–ventral axis in the posterolateral GPe/GPi, and neurons responding to the corresponding regions of the SMA were similarly but less clearly distributed in more anteromedial regions. Moreover, neurons responding to the distal and proximal forelimb MI regions were found along the lateral–medial axis in the STN and the ventral–dorsal axis in the GPe/GPi. Most STN and GPe/GPi neurons showed kinaesthetic responses with similar somatotopic maps. These observations suggest that the somatotopically organized inputs from the MI and SMA are well preserved in the STN and GPe/GPi with partial convergence.     

Listening under difficult conditions: An activation likelihood estimation meta‐analysis

The brain networks supporting speech identification and comprehension under difficult listening conditions are not well specified. The networks hypothesized to underlie effortful listening include regions responsible for executive control. We conducted meta‐analyses of auditory neuroimaging studies to determine whether a common activation pattern of the frontal lobe supports effortful listening under different speech manipulations. Fifty‐three functional neuroimaging studies investigating speech perception were divided into three independent Activation Likelihood Estimate analyses based on the type of speech manipulation paradigm used: Speech‐in‐noise (SIN, 16 studies, involving 224 participants); spectrally degraded speech using filtering techniques (15 studies involving 270 participants); and linguistic complexity (i.e., levels of syntactic, lexical and semantic intricacy/density, 22 studies, involving 348 participants). Meta‐analysis of the SIN studies revealed higher effort was associated with activation in left inferior frontal gyrus (IFG), left inferior parietal lobule, and right insula. Studies using spectrally degraded speech demonstrated increased activation of the insula bilaterally and the left superior temporal gyrus (STG). Studies manipulating linguistic complexity showed activation in the left IFG, right middle frontal gyrus, left middle temporal gyrus and bilateral STG. Planned contrasts revealed left IFG activation in linguistic complexity studies, which differed from activation patterns observed in SIN or spectral degradation studies. Although there were no significant overlap in prefrontal activation across these three speech manipulation paradigms, SIN and spectral degradation showed overlapping regions in left and right insula. These findings provide evidence that there is regional specialization within the left IFG and differential executive networks underlie effortful listening.     

Functional connectivity of cortical motor areas in the resting state in Parkinson's disease

Parkinson's disease (PD) patients have difficulty in initiating movements. Previous studies have suggested that the abnormal brain activity may happen not only during performance of self‐initiated movements but also in the before movement (baseline or resting) state. In the current study, we investigated the functional connectivity of brain networks in the resting state in PD. We chose the rostral supplementary motor area (pre‐SMA) and bilateral primary motor cortex (M1) as “seed” regions, because the pre‐SMA is important in motor preparation, whereas the M1 is critical in motor execution. FMRIs were acquired in 18 patients and 18 matched controls. We found that in the resting state, the pattern of connectivity with both the pre‐SMA or the M1 was changed in PD. Connectivity with the pre‐SMA in patients with PD compared to normal subjects was increased connectivity to the right M1 and decreased to the left putamen, right insula, right premotor cortex, and left inferior parietal lobule. We only found stronger connectivity in the M1 with its own local region in patients with PD compared to controls. Our findings demonstrate that the interactions of brain networks are abnormal in PD in the resting state. There are more connectivity changes of networks related to motor preparation and initiation than to networks of motor execution in PD. We postulate that these disrupted connections indicate a lack of readiness for movement and may be partly responsible for difficulty in initiating movements in PD. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Increased functional connectivity between presupplementary motor area and inferior frontal gyrus associated with the ability of motor response inhibition in obsessive–compulsive disorder

Recent evidence suggests that presupplementary motor area (pre‐SMA) and inferior frontal gyrus (IFG) play an important role in response inhibition. However, no study has investigated the relationship between these brain networks at resting‐state and response inhibition in obsessive–compulsive disorder (OCD). We performed resting‐state functional magnetic resonance imaging scans and then measured the response inhibition of 41 medication‐free OCD patients and 49 healthy control (HC) participants by using the stop‐signal task outside the scanner. We explored the differences between OCD and HC groups in the functional connectivity of pre‐SMA and IFG associated with the ability of motor response inhibition. OCD patients showed a longer stop‐signal reaction time (SSRT). Compared to HC, OCD patients exhibit different associations between the ability of motor response inhibition and the functional connectivity between pre‐SMA and IFG, inferior parietal lobule, dorsal anterior cingulate cortex, insula, and anterior prefrontal cortex. Additional analysis to investigate the functional connectivity difference from the seed ROIs to the whole brain voxels revealed that, compared to HC, OCD exhibited greater functional connectivity between pre‐SMA and IFG. Also, this functional connectivity was positively correlated with the SSRT score. These results provide additional insight into the characteristics of the resting‐state functional connectivity of the regions belonging to the cortico‐striato‐thalamo‐cortical circuit and the cingulo‐opercular salience network, underlying the impaired motor response inhibition of OCD. In particular, we emphasize the importance of altered functional connectivity between pre‐SMA and IFG for the pathophysiology of motor response inhibition in OCD.     

Insula‐based networks in professional musicians: Evidence for increased functional connectivity during resting state fMRI

Despite considerable research on experience‐dependent neuroplasticity in professional musicians, detailed understanding of an involvement of the insula is only now beginning to emerge. We investigated the effects of musical training on intrinsic insula‐based connectivity in professional classical musicians relative to nonmusicians using resting‐state functional MRI. Following a tripartite scheme of insula subdivisions, coactivation profiles were analyzed for the posterior, ventral anterior, and dorsal anterior insula in both hemispheres. While whole‐brain connectivity across all participants confirmed previously reported patterns, between‐group comparisons revealed increased insular connectivity in musicians relative to nonmusicians. Coactivated regions encompassed constituents of large‐scale networks involved in salience detection (e.g., anterior and middle cingulate cortex), affective processing (e.g., orbitofrontal cortex and temporal pole), and higher order cognition (e.g., dorsolateral prefrontal cortex and the temporoparietal junction), whereas no differences were found for the reversed group contrast. Importantly, these connectivity patterns were stronger in musicians who experienced more years of musical practice, including also sensorimotor regions involved in music performance (M1 hand area, S1, A1, and SMA). We conclude that musical training triggers significant reorganization in insula‐based networks, potentially facilitating high‐level cognitive and affective functions associated with the fast integration of multisensory information in the context of music performance. Hum Brain Mapp 38:4834–4849, 2017. © 2017 Wiley Periodicals, Inc.     

Functional and anatomical connectivity abnormalities in left inferior frontal gyrus in schizophrenia

Functional studies in schizophrenia demonstrate prominent abnormalities within the left inferior frontal gyrus (IFG) and also suggest the functional connectivity abnormalities in language network including left IFG and superior temporal gyrus during semantic processing. White matter connections between regions involved in the semantic network have also been indicated in schizophrenia. However, an association between functional and anatomical connectivity disruptions within the semantic network in schizophrenia has not been established. Functional (using levels of processing paradigm) as well as diffusion tensor imaging data from 10 controls and 10 chronic schizophrenics were acquired and analyzed. First, semantic encoding specific activation was estimated, showing decreased activation within the left IFG in schizophrenia. Second, functional time series were extracted from this area, and left IFG specific functional connectivity maps were produced for each subject. In an independent analysis, tract‐based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) values between groups, and to correlate these values with functional connectivity maps. Schizophrenia patients showed weaker functional connectivity within the language network that includes left IFG and left superior temporal sulcus/middle temporal gyrus. FA was reduced in several white matter regions including left inferior frontal and left internal capsule. Finally, left inferior frontal white matter FA was positively correlated with connectivity measures of the semantic network in schizophrenics, but not in controls. Our results indicate an association between anatomical and functional connectivity abnormalities within the semantic network in schizophrenia, suggesting further that the functional abnormalities observed in this disorder might be directly related to white matter disruptions. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Determination of the posterior boundary of Wernicke's area based on multimodal connectivity profiles

Wernicke's area is one of the most important language regions and has been widely studied in both basic research and clinical neurology. However, its exact anatomy has been controversial. In this study, we proposed to address the anatomy of Wernicke's area by investigating different connectivity profiles. First, the posterior superior temporal gyrus (STG), traditionally called “Wernicke's area”, was parcellated into three component subregions with diffusion MRI. Then, whole‐brain anatomical connectivity, resting‐state functional connectivity (RSFC) and meta‐analytic connectivity modeling (MACM) analyses were used to establish the anatomical, resting‐state and task‐related coactivation network of each subregion to identify which subregions participated in the language network. In addition, behavioral domain analysis, meta‐analyses of semantics, execution speech, and phonology and intraoperative electrical stimulation were used to determine which subregions were involved in language processing. Anatomical connectivity, RSFC and MACM analyses consistently identified that the two anterior subregions in the posterior STG primarily participated in the language network, whereas the most posterior subregion in the temporoparietal junction area primarily participated in the default mode network. Moreover, the behavioral domain analyses, meta‐analyses of semantics, execution speech and phonology and intraoperative electrical stimulation mapping also confirmed that only the two anterior subregions were involved in language processing, whereas the most posterior subregion primarily participated in social cognition. Our findings revealed a convergent posterior anatomical border for Wernicke's area and indicated that the brain's functional subregions can be identified on the basis of its specific structural and functional connectivity patterns. Hum Brain Mapp 36:1908–1924, 2015. © 2015 Wiley Periodicals, Inc .     

The role of anterior midcingulate cortex in cognitive motor control

The rostral cingulate cortex has been associated with a multitude of cognitive control functions. Recent neuroimaging data suggest that the anterior midcingulate cortex (aMCC) has a key role for cognitive aspects of movement generation, i.e., intentional motor control. We here tested the functional connectivity of this area using two complementary approaches: (1) resting‐state connectivity of the aMCC based on fMRI scans obtained in 100 subjects, and (2) functional connectivity in the context of explicit task conditions using meta‐analytic connectivity modeling (MACM) over 656 imaging experiment. Both approaches revealed a convergent functional network architecture of the aMCC with prefrontal, premotor and parietal cortices as well as anterior insula, area 44/45, cerebellum and dorsal striatum. To specifically test the role of the aMCC's task‐based functional connectivity in cognitive motor control, separate MACM analyses were conducted over “cognitive” and “action” related experimental paradigms. Both analyses confirmed the same task‐based connectivity pattern of the aMCC. While the “cognition” domain showed higher convergence of activity in supramodal association areas in prefrontal cortex and anterior insula, “action” related experiments yielded higher convergence in somatosensory and premotor areas. Secondly, to probe the functional specificity of the aMCC's convergent functional connectivity, it was compared with a neural network of intentional movement initiation. This exemplary comparison confirmed the involvement of the state independent FC network of the aMCC in the intentional generation of movements. In summary, the different experiments of the present study suggest that the aMCC constitute a key region in the network realizing intentional motor control. Hum Brain Mapp 35:2741–2753, 2014. © 2013 Wiley Periodicals, Inc .     

The intrinsic resting state voice network in Parkinson's disease

Over 90 percent of patients with Parkinson's disease experience speech‐motor impairment, namely, hypokinetic dysarthria characterized by reduced pitch and loudness. Resting‐state functional connectivity analysis of blood oxygen level‐dependent functional magnetic resonance imaging is a useful measure of intrinsic neural functioning. We utilized resting‐state functional connectivity modeling to analyze the intrinsic connectivity in patients with Parkinson's disease within a vocalization network defined by a previous meta‐analysis of speech (Brown et al., 2009). Functional connectivity of this network was assessed in 56 patients with Parkinson's disease and 56 gender‐, age‐, and movement‐matched healthy controls. We also had item 5 and 18 of the UPDRS, and the PDQ‐39 Communication subscale available for correlation with the voice network connectivity strength in patients. The within‐group analyses of connectivity patterns demonstrated a lack of subcortical–cortical connectivity in patients with Parkinson's disease. At the cortical level, we found robust (homotopic) interhemispheric connectivity but only inconsistent evidence for many intrahemispheric connections. When directly contrasted to the control group, we found a significant reduction of connections between the left thalamus and putamen, and cortical motor areas, as well as reduced right superior temporal gyrus connectivity. Furthermore, most symptom measures correlated with right putamen, left cerebellum, left superior temporal gyrus, right premotor, and left Rolandic operculum connectivity in the voice network. The results reflect the importance of (right) subcortical nodes and the superior temporal gyrus in Parkinson's disease, enhancing our understanding of the neurobiological underpinnings of vocalization impairment in Parkinson's disease. Hum Brain Mapp 36:1951–1962, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Meta‐analytic evidence for a joint neural mechanism underlying response inhibition and state anger

Although anger may weaken response inhibition (RI) by allowing outbursts to bypass deliberate processing, it is equally likely that RI deficits precipitate a state of anger (SA). In adolescents, for instance, anger occurs more frequently and often leads to escalating aggressive behaviors. Even though RI is considered a key component in explaining individual differences in SA expression, the neural overlap between SA and RI remains elusive. Here, we aimed to meta‐analytically revisit and update the neural correlates of motor RI, to determine a consistent neural architecture of SA, and to identify their joint neural network. Considering that inhibitory abilities follow a protracted maturation until early adulthood, we additionally computed RI meta‐analyses in youths and adults. Using activation likelihood estimation, we calculated twelve meta‐analyses across 157 RI and 39 SA experiments on healthy individuals. Consistent with previous findings, RI was associated with a broad frontoparietal network including the anterior insula/inferior frontal gyrus (aI/IFG), premotor and midcingulate cortices, extending into right temporoparietal areas. Youths showed convergent activity in right midcingulate and medial prefrontal areas, left aI/IFG, and the temporal poles. SA, on the other hand, reliably recruited the right aI/IFG and anterior cingulate cortex. Conjunction analyses between RI and SA yielded a single convergence cluster in the right aI/IFG. While frontoparietal networks and bilateral aI are ubiquitously recruited during RI, the right aI/IFG cluster likely represents a node in a dynamically‐adjusting monitoring network that integrates salient information thereby facilitating the execution of goal‐directed behaviors under highly unpredictable scenarios.     

Characterizing the role of the pre‐SMA in the control of speed/accuracy trade‐off with directed functional connectivity mapping and multiple solution reduction

Several plausible theories of the neural implementation of speed/accuracy trade‐off (SAT), the phenomenon in which individuals may alternately emphasize speed or accuracy during the performance of cognitive tasks, have been proposed, and multiple lines of evidence point to the involvement of the pre‐supplemental motor area (pre‐SMA). However, as the nature and directionality of the pre‐SMA's functional connections to other regions involved in cognitive control and task processing are not known, its precise role in the top‐down control of SAT remains unclear. Although recent advances in cross‐sectional path modeling provide a promising way of characterizing these connections, such models are limited by their tendency to produce multiple equivalent solutions. In a sample of healthy adults (N = 18), the current study uses the novel approach of Group Iterative Multiple Model Estimation for Multiple Solutions (GIMME‐MS) to assess directed functional connections between the pre‐SMA, other regions previously linked to control of SAT, and regions putatively involved in evidence accumulation for the decision task. Results reveal a primary role of the pre‐SMA for modulating activity in regions involved in the decision process but suggest that this region receives top‐down input from the DLPFC. Findings also demonstrate the utility of GIMME‐MS and solution‐reduction methods for obtaining valid directional inferences from connectivity path models.     

Altered functional connectivity of the subthalamic nucleus during self-initiated movement in Parkinson's disease

Background and purpose

Patients with Parkinson's disease (PD) have difficulty performing self-initiated movements. The neural mechanism of this deficiency remains unclear. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate the functional connectivity of the subthalamic nucleus (STN) during self-initiated movement in patients with PD.

The human subthalamic nucleus and globus pallidus internus differentially encode reward during action control

The subthalamic nucleus (STN) and globus pallidus internus (GPi) have recently been shown to encode reward, but few studies have been performed in humans. We investigated STN and GPi encoding of reward and loss (i.e., valence) in humans with Parkinson's disease. To test the hypothesis that STN and GPi neurons would change their firing rate in response to reward‐ and loss‐related stimuli, we recorded the activity of individual neurons while participants performed a behavioral task. In the task, action choices were associated with potential rewarding, punitive, or neutral outcomes. We found that STN and GPi neurons encode valence‐related information during action control, but the proportion of valence‐responsive neurons was greater in the STN compared to the GPi. In the STN, reward‐related stimuli mobilized a greater proportion of neurons than loss‐related stimuli. We also found surprising limbic overlap with the sensorimotor regions in both the STN and GPi, and this overlap was greater than has been previously reported. These findings may help to explain alterations in limbic function that have been observed following deep brain stimulation therapy of the STN and GPi. Hum Brain Mapp 38:1952–1964, 2017 . © 2017 Wiley Periodicals, Inc.     

A tug of war: antagonistic effective connectivity patterns over the motor cortex and the severity of motor symptoms in Gilles de la Tourette syndrome

We tested the hypothesis that Gilles de la Tourette syndrome (GTS) is characterized by perturbed connectivity within cortico–subcortical motor networks. To this end, we performed a dynamic causal modelling (DCM) analysis of fMRI data collected during a finger opposition task in 24 normal controls and 24 GTS patients. The DCM analysis allowed us to assess whether any GTS‐specific patterns of brain activity were related to intrinsic and/or to task‐dependent connectivity. While no abnormalities were found for task‐dependent connectivity, intrinsic connectivity was abnormally increased in the premotor network, with stronger connections from the supplementary motor area (SMA), from the dorsolateral premotor cortex and from the putamen to the right superior frontal gyrus, an area where GTS showed over‐activation in a previous univariate analysis. We also found a positive correlation between the connectivity strength from the right basal ganglia to the right primary motor cortex (M1) and disease severity measured by the Yale Global Tic Severity Scale (YGTSS). This pattern was mirrored by a negative correlation between the connection strength from the right SMA to the right area M1 and the YGTSS score. These two reverse correlation effects showed a specific relationship with individual disease severity: the greater the imbalance between subcortical and premotor connectivity towards area M1, the higher the YGTSS score. These results reveal the existence of perturbed intrinsic connectivity patterns in the motor networks of GTS patients with two competing forces operating in a tug of war‐like mechanism: aberrant subcortical afferents to M1, compensated for by inputs from the premotor cortex.     

Dynamic functional network connectivity reveals unique and overlapping profiles of insula subdivisions

The human insular cortex consists of functionally diverse subdivisions that engage during tasks ranging from interoception to cognitive control. The multiplicity of functions subserved by insular subdivisions calls for a nuanced investigation of their functional connectivity profiles. Four insula subdivisions (dorsal anterior, dAI; ventral, VI; posterior, PI; middle, MI) derived using a data‐driven approach were subjected to static‐ and dynamic functional network connectivity (s‐FNC and d‐FNC) analyses. Static‐FNC analyses replicated previous work demonstrating a cognition‐emotion‐interoception division of the insula, where the dAI is functionally connected to frontal areas, the VI to limbic areas, and the PI and MI to sensorimotor areas. Dynamic‐FNC analyses consisted of k‐means clustering of sliding windows to identify variable insula connectivity states. The d‐FNC analysis revealed that the most frequently occurring dynamic state mirrored the cognition‐emotion‐interoception division observed from the s‐FNC analysis, with less frequently occurring states showing overlapping and unique subdivision connectivity profiles. In two of the states, all subdivisions exhibited largely overlapping profiles, consisting of subcortical, sensory, motor, and frontal connections. Two other states showed the dAI exhibited a unique connectivity profile compared with other insula subdivisions. Additionally, the dAI exhibited the most variable functional connections across the s‐FNC and d‐FNC analyses, and was the only subdivision to exhibit dynamic functional connections with regions of the default mode network. These results highlight how a d‐FNC approach can capture functional dynamics masked by s‐FNC approaches, and reveal dynamic functional connections enabling the functional flexibility of the insula across time. Hum Brain Mapp 37:1770–1787, 2016. © 2016 Wiley Periodicals, Inc .     

An investigation of the structural,connectional, and functional subspecialization in the human amygdala

Although the amygdala complex is a brain area critical for human behavior, knowledge of its subspecialization is primarily derived from experiments in animals. We here employed methods for large‐scale data mining to perform a connectivity‐derived parcellation of the human amygdala based on whole‐brain coactivation patterns computed for each seed voxel. Voxels within the histologically defined human amygdala were clustered into distinct groups based on their brain‐wide coactivation maps. Using this approach, connectivity‐based parcellation divided the amygdala into three distinct clusters that are highly consistent with earlier microstructural distinctions. Meta‐analytic connectivity modelling then revealed the derived clusters' brain‐wide connectivity patterns, while meta‐data profiling allowed their functional characterization. These analyses revealed that the amygdala's laterobasal nuclei group was associated with coordinating high‐level sensory input, whereas its centromedial nuclei group was linked to mediating attentional, vegetative, and motor responses. The often‐neglected superficial nuclei group emerged as particularly sensitive to olfactory and probably social information processing. The results of this model‐free approach support the concordance of structural, connectional, and functional organization in the human amygdala and point to the importance of acknowledging the heterogeneity of this region in neuroimaging research. Hum Brain Mapp 34:3247–3266, 2013. © 2012 Wiley Periodicals, Inc.     

Meta‐analytic and functional connectivity evidence from functional magnetic resonance imaging for an anterior to posterior gradient of function along the hippocampal axis

There is considerable evidence from non‐human animal studies that the anterior and posterior regions of the hippocampus have different anatomical connections and support different behavioural functions. Although there are some recent human studies using functional magnetic resonance imaging (fMRI) that have addressed this idea directly in the memory and spatial processing domains and provided support for it, there has been no broader meta‐analysis of the fMRI literature to determine if there is consistent evidence for functional dissociations in anterior and posterior hippocampus across all of the different cognitive domains in which the hippocampus participates. The purpose of this review is to address this gap in our knowledge using three approaches. One approach involved PubMed searches to identify relevant fMRI papers reporting hippocampal activation during episodic encoding and retrieval, semantic retrieval, working memory, spatial navigation, simulation/scene construction, transitive inference, and social cognition tasks. The second was to use a large meta‐analytic database (neurosynth) to find text terms and coactivation maps associated with the anterior and posterior hippocampal regions identified in the literature search. The third approach was to contrast the resting‐state functional connectivity of the anterior and posterior hippocampal regions using a publicly available database that includes a large sample of adults. These three approaches provided converging evidence that not only are cognitive processes differently distributed along the hippocampal axis, but there also are distinct areas coactivated and functionally connected with the anterior and posterior segments. This anterior/posterior distinction involving multiple cognitive domains is consistent with the animal literature and provides strong support from fMRI for the idea of functional dissociations across the long axis of the hippocampus.     

The brain network reflecting bodily self-consciousness: a functional connectivity study

Several brain regions are important for processing self-location and first-person perspective, two important aspects of bodily self-consciousness. However, the interplay between these regions has not been clarified. In addition, while self-location and first-person perspective in healthy subjects are associated with bilateral activity in temporoparietal junction (TPJ), disturbed self-location and first-person perspective result from damage of only the right TPJ. Identifying the involved brain network and understanding the role of hemispheric specializations in encoding self-location and first-person perspective, will provide important information on system-level interactions neurally mediating bodily self-consciousness. Here, we used functional connectivity and showed that right and left TPJ are bilaterally connected to supplementary motor area, ventral premotor cortex, insula, intraparietal sulcus and occipitotemporal cortex. Furthermore, the functional connectivity between right TPJ and right insula had the highest selectivity for changes in self-location and first-person perspective. Finally, functional connectivity revealed hemispheric differences showing that self-location and first-person perspective modulated the connectivity between right TPJ, right posterior insula, and right supplementary motor area, and between left TPJ and right anterior insula. The present data extend previous evidence on healthy populations and clinical observations in neurological deficits, supporting a bilateral, but right-hemispheric dominant, network for bodily self-consciousness.