Large-scale visuomotor integration in the cerebral cortex

Efficient visuomotor behavior depends on integrated processing by the visual and motor systems of the cerebral cortex. Yet, many previous cortical neurophysiology studies have examined the visual and motor modalities in isolation, largely ignoring questions of large-scale cross-modal integration. To address this issue, we analyzed event-related local field potentials simultaneously recorded from multiple visual, motor, and executive cortical sites in monkeys performing a visuomotor pattern discrimination task. The timing and cortical location of four aspects of event-related activities were examined: stimulus-evoked activation onset, stimulus-specific processing, stimulus category-specific processing, and response-specific processing. Activations appeared earliest in striate cortex and rapidly thereafter in other visual areas. Stimulus-specific processing began early in most visual cortical areas, some at activation onset. Early onset latencies were also observed in motor, premotor, and prefrontal areas, some as early as in striate cortex, but these early-activating frontal sites did not show early stimulus-specific processing. Response-specific processing began around 150 ms poststimulus in widespread cortical areas, suggesting that perceptual decision formation and response selection arose through concurrent processes of visual, motor, and executive areas. The occurrence of stimulus-specific and stimulus category-specific differences after the onset of response-specific processing suggests that sensory and motor stages of visuomotor processing overlapped in time.     

Cortical connections of the macaque anterior intraparietal (AIP) area

We traced the cortical connections of the anterior intraparietal (AIP) area, which is known to play a crucial role in visuomotor transformations for grasping. AIP displayed major connections with 1) areas of the inferior parietal lobule convexity, the rostral part of the lateral intraparietal area and the SII region; 2) ventral visual stream areas of the lower bank of the superior temporal sulcus and the middle temporal gyrus; and 3) the premotor area F5 and prefrontal areas 46 and 12. Additional connections were observed with the caudal intraparietal area and the ventral part of the frontal eye field. This study suggests that visuomotor transformations for object-oriented actions, processed in AIP, rely not only on dorsal visual stream information related to the object's physical properties but also on ventral visual stream information related to object identity. The identification of direct anatomical connections with the inferotemporal cortex suggests that AIP also has a unique role in linking the parietofrontal network of areas involved in sensorimotor transformations for grasping with areas involved in object recognition. Thus, AIP could represent a crucial node in a cortical circuit in which hand-related sensory and motor signals gain access to representations of object identity for tactile object recognition.     

Reading salt activates gustatory brain regions: FMRI evidence for semantic grounding in a novel sensory modality

Because many words are typically used in the context of their referent objects and actions, distributed cortical circuits for these words may bind information about their form with perceptual and motor aspects of their meaning. Previous work has demonstrated such semantic grounding for sensorimotor, visual, auditory, and olfactory knowledge linked to words, which is manifest in activation of the corresponding areas of the cortex. Here, we explore the brain basis of gustatory semantic links of words whose meaning is primarily related to taste. In a blocked functional magnetic resonance imaging design, Spanish taste words and control words matched for a range of factors (including valence, arousal, imageability, frequency of use, number of letters and syllables) were presented to 59 right-handed participants in a passive reading task. Whereas all the words activated the left inferior frontal (BA44/45) and the posterior middle and superior temporal gyri (BA21/22), taste-related words produced a significantly stronger activation in these same areas and also in the anterior insula, frontal operculum, lateral orbitofrontal gyrus, and thalamus among others. As these areas comprise primary and secondary gustatory cortices, we conclude that the meaning of taste words is grounded in distributed cortical circuits reaching into areas that process taste sensations.     

Distribution of cortical activation during visuospatial n-back tasks as revealed by functional magnetic resonance imaging

Human neuroimaging studies conducted during visuospatial working memory tasks have inconsistently detected activation in the prefrontal cortical areas depending presumably on the type of memory and control tasks employed. We used functional magnetic resonance imaging to study brain activation related to the performance of a visuospatial n-back task with different memory loads (0-back, 1-back and 2-back tasks). Comparison of the 2-back versus 0-back tasks revealed consistent, bilateral activation in the medial frontal gyrus (MFG), superior frontal sulcus and adjacent cortical tissue (SFS/SFG) in all subjects and in six out of seven subjects in the intraparietal sulcus (IPS). Activation was also detected in the inferior frontal gyrus, medially in the superior frontal gyrus, precentral gyrus, superior and inferior parietal lobuli, occipital visual association areas, anterior and posterior cingulate areas and in the insula. Comparison between the 1- back versus 0-back tasks revealed activation only in a few brain areas. Activation in the MFG, SFS/SFG and IPS appeared dependent on memory load. The results suggest that the performance of a visuospatial working memory task engages a network of distributed brain areas and that areas in the dorsal visual pathway are engaged in mnemonic processing of visuospatial information.      

Human neural systems for conceptual knowledge of proper object use: a functional magnetic resonance imaging study

Ideational apraxia is characterized by impaired knowledge of action concepts and proper object usage. The present functional magnetic resonance imaging study aimed at investigating the neural system underlying conceptual knowledge for proper object use in healthy subjects, when the effects of visuospatial properties and perceptual modality were taken into account. Subjects performed semantic decision tasks requiring retrieval of knowledge about either object functional purposes (functional task) or visuospatial object properties (visuospatial task) and perceptual control tasks. The semantic tasks were performed with pairs of either written object names or object drawings. Activation for the functional task in common for words and pictures, compared with the visuospatial and control tasks, was found in left parietal-temporal-occipital (PTO) junction, inferior frontal, anterior dorsal premotor, and presupplementary motor areas. Ventral inferior frontal cortex activation correlated negatively with reaction time in the functional condition. No specific activation characterized the visuospatial task compared with the functional task. The conceptual tasks, compared with the control tasks, demonstrated overlapping activation in left PTO junction, prefrontal, dorsal premotor, cuneus, and inferior temporal areas. These results outline the neural processes underlying conceptual knowledge for proper object use. The left ventral inferior frontal gyrus might facilitate behavioral decisions regarding functional/pragmatical object properties.     

The role of semantics and grammatical class in the neural representation of words

On the basis of neuropsychological and functional imaging evidence, meaning and grammatical class (particularly the verb-noun distinction) have been proposed as organizational principles of linguistic knowledge in the brain. However, previous studies investigating verb and noun processing have been confounded by the presence of systematic correlations between word meaning and grammatical class. In this positron emission tomography study, we investigated implicit word processing using stimuli that allowed the effects of semantic and grammatical properties to be examined independently, without grammatical-semantic confounds. We found that left hemisphere cortical activation during single-word processing was modulated by word meaning, but not by grammatical class. Motor word processing produced significant activation in left precentral gyrus, whereas sensory word processing produced significant activation in left inferior temporal and inferior frontal regions. In contrast to previous studies, there were no effects of grammatical class in left inferior frontal gyrus (IFG). Instead, we found semantic-based differences within left IFG: anterior, but not posterior, left IFG regions responded preferentially to sensory words. These findings demonstrate that the neural substrates of implicit word processing are determined by semantic rather than grammatical properties and suggest that word comprehension involves the activation of modality-specific representations linked to word meaning.     

Segregating semantic and syntactic aspects of processing in the human brain: an fMRI investigation of different word types

The processing of single words that varied in their semantic (concrete/abstract word) and syntactic (content/function word) status was investigated under different task demands (semantic/ syntactic task) in an event-related functional magnetic resonance imaging experiment. Task demands to a large degree determined which subparts of the neuronal network supporting word processing were activated. Semantic task demands selectively activated the left pars triangularis of the inferior frontal gyrus (BA 45) and the posterior part of the left middle/superior temporal gyrus (BA 21/22/37). In contrast, syntactic processing requirements led to an increased activation in the inferior tip of the left frontal operculum (BA 44) and the cortex lining the junction of the inferior frontal and inferior precentral sulcus (BA 44/6). Moreover, for these latter areas a word class by concreteness interaction was observed when a syntactic judgement was required. This interaction can be interpreted as a prototypicality effect: non-prototypical members of a word class, i.e. concrete function words and abstract content words, showed a larger activation than prototypical members, i.e. abstract function words and concrete content words. The combined data suggest that the activation pattern underlying word processing is predicted neither by syntactic class nor semantic concreteness but, rather, by task demands focusing either on semantic or syntactic aspects. Thus, our findings that semantic and syntactic aspects of processing are both functionally distinct and involve different subparts of the neuronal network underlying word processing support a domain-specific organization of the language system.     

Neural correlates of the spontaneous phase transition during bimanual coordination

Repetitive bimanual finger-tapping movements tend toward mirror symmetry: There is a spontaneous transition from less stable asymmetrical movement patterns to more stable symmetrical ones under frequency stress but not vice versa. During this phase transition, the interaction between the signals controlling each hand (cross talk) is expected to be prominent. To depict the regions of the brain in which cortical cross talk occurs during bimanual coordination, we conducted event-related functional magnetic resonance imaging using a bimanual repetitive-tapping task. Transition-related activity was found in the following areas: the bilateral ventral premotor cortex, inferior frontal gyrus, middle frontal gyrus, inferior parietal lobule, insula, and thalamus; the right rostral portion of the dorsal premotor cortex and midbrain; the left cerebellum; and the presupplementary motor area, rostral cingulate zone, and corpus callosum. These regions were discrete from those activated by bimanual movement execution. The phase-transition-related activation was right lateralized in the prefrontal, premotor, and parietal regions. These findings suggest that the cortical neural cross talk occurs in the distributed networks upstream of the primary motor cortex through asymmetric interhemispheric interaction.     

Idiom comprehension: a prefrontal task?

We investigated the neural correlates of idiomatic sentence processing using event-related functional magnetic resonance imaging. Twenty-two healthy subjects were presented with 62 literal sentences and 62 idiomatic sentences, each followed by a picture and were required to judge whether the sentence matched the picture or not. A common network of cortical activity was engaged by both conditions, with the nonliteral task eliciting overall greater activation, both in terms of magnitude and spatial extent. The network that was specifically activated by the nonliteral condition involved the left temporal cortex, the left superior medial frontal gyrus (Brodmann area 9), and the left inferior frontal gyrus (IFG). Activations were also present in the right superior and middle temporal gyri and temporal pole and in the right IFG. In contrast, literal sentences selectively activated the left inferior parietal lobule and the right supramarginal gyrus. An analysis of effective connectivity indicated that the medial prefrontal area significantly increased the connection between frontotemporal areas bilaterally during idiomatic processing. Overall, the present findings indicate a crucial role of the prefrontal cortex in idiom comprehension, which could reflect the selection between alternative sentence meanings.     

静息态fMRI评估急性酒精暴露对恒河猴脑功能的影响

目的采用静息态fMRI基于分数低频振荡幅度(fALFF)方法评估急性酒精暴露后恒河猴脑功能改变。方法分别对7只健康雄性恒河猴于静脉注射酒精前及注射后10、28、46min进行BOLD fMRI序列及3D结构像扫描,采用fALFF算法获得并比较4个时间点fALFF差异的脑区。结果 4个时间点fALFF总体差异显著的脑区为右侧中央后回、右侧岛叶、右侧小脑、左侧海马旁回、双侧额下回、小脑蚓部、右枕叶、楔前叶、左侧缘上回(P均0.05);静脉注射酒精后fALFF值减低的脑区为双侧额上回、右侧额下回、右侧梭状回、右侧角回、双侧颞上回、右枕叶、左侧外侧沟、左侧中央后回、左侧楔状叶、左侧丘脑、左侧岛叶、前扣带回(P均0.05);静脉注射酒精后fALFF值增高的脑区为右侧额下回、右侧颞中回(P均0.05)。结论酒精暴露急性期脑代谢活动发生显著变化,主要涉及默认网络、奖赏及情绪加工系统、视听皮层等。     

Dominance for vestibular cortical function in the non-dominant hemisphere

The aim of this (15)O-labelled H(2)O bolus positron emission tomography (PET) study was to analyse the hemispheric dominance of the vestibular cortical system. Therefore, the differential effects of caloric vestibular stimulation (right or left ear irrigation with warm water at 44 degrees C) on cortical and subcortical activation were studied in 12 right-handed and 12 left-handed healthy volunteers. Caloric irrigation induces a direction-specific sensation of rotation and nystagmus. Significant regional cerebral blood flow increases were found in a network within both hemispheres, including the superior frontal gyrus/sulcus, the precentral gyrus and the inferior parietal lobule with the supramarginal gyrus. These areas correspond best to the cortical ocular motor centres, namely the prefrontal cortex, the frontal eye field and the parietal eye field, known to be involved in the processing of caloric nystagmus. Furthermore, distinct temporo-parietal activations could be separated in the posterior part of the insula with the adjacent superior temporal gyrus, the inferior parietal lobule and precuneus. These areas fit best to the human homologues of multisensory vestibular cortex areas identified in the monkey and correspond to the parieto-insular vestibular cortex (PIVC), the visual temporal sylvian area (VTS) and areas 7 and 6. Further cortical activations were seen in the anterior insula, the inferior frontal gyrus and anterior cingulum. The subcortical activation pattern in the putamen, thalamus and midbrain is consistent with the organization of efferent ocular motor pathways. Cortical and subcortical activation of the described areas was bilateral during monaural stimulation, but predominant in the hemisphere ipsilateral to the stimulated ear and exhibited a significant right hemispheric dominance for vestibular and ocular motor structures in right-handed volunteers. Similarly, a significant left hemispheric dominance was found in the 12 left-handed volunteers. Thus, this PET study showed for the first time that cortical and subcortical activation by vestibular caloric stimulation depends (i) on the handedness of the subjects and (ii) on the side of the stimulated ear. Maximum activation was therefore found when the non-dominant hemisphere was ipsilateral to the stimulated ear, i.e. in the right hemisphere of right-handed subjects during caloric irrigation of the right ear and in the left hemisphere of left-handed subjects during caloric irrigation of the left ear. The localization of handedness and vestibular dominance in opposite hemispheres might conceivably indicate that the vestibular system and its hemispheric dominance, which matures earlier during ontogenesis, determine right- or left-handedness.     

Sound to language: different cortical processing for first and second languages in elementary school children as revealed by a large-scale study using fNIRS

A large-scale study of 484 elementary school children (6-10 years) performing word repetition tasks in their native language (L1-Japanese) and a second language (L2-English) was conducted using functional near-infrared spectroscopy. Three factors presumably associated with cortical activation, language (L1/L2), word frequency (high/low), and hemisphere (left/right), were investigated. L1 words elicited significantly greater brain activation than L2 words, regardless of semantic knowledge, particularly in the superior/middle temporal and inferior parietal regions (angular/supramarginal gyri). The greater L1-elicited activation in these regions suggests that they are phonological loci, reflecting processes tuned to the phonology of the native language, while phonologically unfamiliar L2 words were processed like nonword auditory stimuli. The activation was bilateral in the auditory and superior/middle temporal regions. Hemispheric asymmetry was observed in the inferior frontal region (right dominant), and in the inferior parietal region with interactions: low-frequency words elicited more right-hemispheric activation (particularly in the supramarginal gyrus), while high-frequency words elicited more left-hemispheric activation (particularly in the angular gyrus). The present results reveal the strong involvement of a bilateral language network in children's brains depending more on right-hemispheric processing while acquiring unfamiliar/low-frequency words. A right-to-left shift in laterality should occur in the inferior parietal region, as lexical knowledge increases irrespective of language.     

The functional neuroanatomy of metrical stress evaluation of perceived and imagined spoken words

We hypothesized that areas in the temporal lobe that have been implicated in the phonological processing of spoken words would also be activated during the generation and phonological processing of imagined speech. We tested this hypothesis using functional magnetic resonance imaging during a behaviorally controlled task of metrical stress evaluation. Subjects were presented with bisyllabic words and had to determine the alternation of strong and weak syllables. Thus, they were required to discriminate between weak-initial words and strong-initial words. In one condition, the stimuli were presented auditorily to the subjects (by headphones). In the other condition the stimuli were presented visually on a screen and subjects were asked to imagine hearing the word. Results showed activation of the supplementary motor area, inferior frontal gyrus (Broca's area) and insula in both conditions. In the superior temporal gyrus (STG) and in the superior temporal sulcus (STS) strong activation was observed during the auditory (perceptual) condition. However, a region located in the posterior part of the STS/STG also responded during the imagery condition. No activation of this same region of the STS was observed during a control condition which also involved processing of visually presented words, but which required a semantic decision from the subject. We suggest that processing of metrical stress, with or without auditory input, relies in part on cortical interface systems located in the posterior part of STS/STG. These results corroborate behavioral evidence regarding phonological loop involvement in auditory-verbal imagery.     

The effects of feature attention on prestimulus cortical activity in the human visual system

Covert attention affects prestimulus activity in the visual cortex. Although most studies investigating neural mechanisms of attention have focused on the effects of spatial attention, attention can also be directed to particular features. To investigate the spatiotemporal nature of feature attention, we measured subjects' brain activity using magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) while subjects attended to color or motion of a stimulus based on a visual cue, which was presented 1 s before the stimulus onset. We used the hierarchical Bayesian method that allows us to estimate cortical currents with MEG and fMRI data in the order of millimeters and milliseconds. When subjects attended to color, activity within the color-sensitive area (fusiform gyrus) was selectively enhanced within the prestimulus period. By contrast, when subjects attended to motion, activity within the motion-sensitive area (middle temporal gyrus) was selectively enhanced during this period. This effect was not seen in frontal, parietal, and lower visual areas. Additionally, this effect was transient rather than sustained, suggesting that it differs from temporal aspects of spatial attention. These results suggest that, although both spatial and feature attention modulate prestimulus activity within specific visual areas, neural mechanisms underlying these effects might be different.     

Cortical connections of area V4 in the macaque

To determine the locus, full extent, and topographic organization of cortical connections of area V4 (visual area 4), we injected anterograde and retrograde tracers under electrophysiological guidance into 21 sites in 9 macaques. Injection sites included representations ranging from central to far peripheral eccentricities in the upper and lower fields. Our results indicated that all parts of V4 are connected with occipital areas V2 (visual area 2), V3 (visual area 3), and V3A (visual complex V3, part A), superior temporal areas V4t (V4 transition zone), MT (medial temporal area), and FST (fundus of the superior temporal sulcus [STS] area), inferior temporal areas TEO (cytoarchitectonic area TEO in posterior inferior temporal cortex) and TE (cytoarchitectonic area TE in anterior temporal cortex), and the frontal eye field (FEF). By contrast, mainly peripheral field representations of V4 are connected with occipitoparietal areas DP (dorsal prelunate area), VIP (ventral intraparietal area), LIP (lateral intraparietal area), PIP (posterior intraparietal area), parieto-occipital area, and MST (medial STS area), and parahippocampal area TF (cytoarchitectonic area TF on the parahippocampal gyrus). Based on the distribution of labeled cells and terminals, projections from V4 to V2 and V3 are feedback, those to V3A, V4t, MT, DP, VIP, PIP, and FEF are the intermediate type, and those to FST, MST, LIP, TEO, TE, and TF are feedforward. Peripheral field projections from V4 to parietal areas could provide a direct route for rapid activation of circuits serving spatial vision and spatial attention. By contrast, the predominance of central field projections from V4 to inferior temporal areas is consistent with the need for detailed form analysis for object vision.     

Spontaneous activity associated with primary visual cortex: a resting-state FMRI study

Brain functions during the resting state have attracted considerable attention in the past several years. However, little has been known about spontaneous activity in the sensory cortices in the task-free state. This study used functional magnetic resonance imaging (fMRI) to investigate the existence of spontaneous activity in the primary visual areas (PVA) of normal-sighted subjects and to explore the physiological implications of such activity. Our results revealed that we were able to detect spontaneous activity, which was nonrandom in that it was distinctly clustered both temporally and spatially in the PVA of each subject. In addition, the neural network associated with the PVA-related spontaneous activity included the visual association areas, the precuneus, the precentral/postcentral gyrus, the middle frontal gyrus, the fusiform gyrus, the inferior/middle temporal gyrus, and the parahippocampal gyrus. After considering the functions of these regions, we speculated that the PVA-related spontaneous activity may be associated with memory-related mental imagery and/or visual memory consolidation processes. These findings confirm the presence of spontaneous activity in the PVA and related brain areas. This confirmation supports the perspective that brain is a system intrinsically operating on its own, and sensory information interacts with rather than determines the operation of the system.     

Nouns and verbs in the intact brain: evidence from event-related potentials and high-frequency cortical responses.

Lesion evidence indicates that words from different lexical categories, such as nouns and verbs, may have different cortical counterparts. In this study, processing of nouns and verbs was investigated in the intact brain using (i) behavioral measures, (ii) stimulus-triggered event-related potentials and (iii) high-frequency electrocortical responses in the gamma band. Nouns and verbs carefully matched for various variables, including word frequency, length, arousal and valence, were presented in a lexical decision task while electrocortical responses were recorded. In addition, information about cognitive processing of these stimuli was obtained using questionnaires and reaction times. As soon as approximately 200 ms after stimulus onset, event-related potentials disclosed electrocortical differences between nouns and verbs over widespread cortical areas. In a later time window, 500-800 ms after stimulus onset, there was a significant difference between high-frequency responses in the 30 Hz range. Difference maps obtained from both event-related potentials and high-frequency responses revealed strong between-category differences of signals recorded above motor and visual cortices. Behavioral data suggest that these different physiological responses are related to semantic associations (motor or visual) elicited by these word groups. Our results are consistent with a neurobiological model of language representation postulating cell assemblies with distinct cortical topographies as biological counterparts of words. Assemblies representing nouns referring to visually perceived objects may include neurons in visual cortices, and assemblies representing action verbs may include additional neurons in motor, premotor and prefrontal cortices. Event-related potentials and high-frequency responses are proposed to indicate two different functional states of cell assemblies: initial full activation ('ignition') and continuous reverberatory activity.     

Neural correlates of different types of deception: an fMRI investigation

Deception is a complex cognitive activity, and different types of lies could arise from different neural systems. We investigated this possibility by first classifying lies according to two dimensions, whether they fit into a coherent story and whether they were previously memorized. fMRI revealed that well-rehearsed lies that fit into a coherent story elicit more activation in right anterior frontal cortices than spontaneous lies that do not fit into a story, whereas the opposite pattern occurs in the anterior cingulate and in posterior visual cortex. Furthermore, both types of lies elicited more activation than telling the truth in anterior prefrontal cortices (bilaterally), the parahippocampal gyrus (bilaterally), the right precuneus, and the left cerebellum. At least in part, distinct neural networks support different types of deception.     

Prefrontal selection and medial temporal lobe reactivation in retrieval of short-term verbal information

Both the prefrontal cortex (PFC) and medial temporal lobe (MTL) are involved in memory retrieval. Here we distinguish between their roles by manipulating demand for interference resolution and reactivation of maintained information. Subjects were tested on a letter working memory task with distractors. When the memory delay was interrupted with letter distractors, there was higher activity in the middle frontal gyrus at retrieval compared to when the delay was interrupted by number distractors, suggesting the role of the PFC in interference resolution. By contrast, activity in the parahippocampal gyrus did not differ between the two conditions. The two structures were then compared using the dataset of our previous study on memory reactivation, where subjects performed a letter working memory task with arithmetic distractors or non-distractors. The activity in the parahippocampal gyrus at retrieval was higher when distractors interrupted rehearsal than when the intervening task was non-distracting and subjects continued to rehearse, suggesting the role of the MTL in reactivating the stored information. By contrast, the activity in the middle frontal gyrus did not differ between the two conditions. Taking these results together, we have shown the double dissociation between the PFC and MTL in memory retrieval.     

The anatomical connections of the macaque monkey orbitofrontal cortex. A review

The orbitofrontal cortex (OfC) is a heterogeneous prefrontal sector selectively connected with a wide constellation of other prefrontal, limbic, sensory and premotor areas. Among the limbic cortical connections, the ones with the hippocampus and parahippocampal cortex are particularly salient. Sensory cortices connected with the OfC include areas involved in olfactory, gustatory, somatosensory, auditory and visual processing. Subcortical structures with prominent OfC connections include the amygdala, numerous thalamic nuclei, the striatum, hypothalamus, periaqueductal gray matter, and biochemically specific cell groups in the basal forebrain and brainstem. Architectonic and connectional evidence supports parcellation of the OfC. The rostrally placed isocortical sector is mainly connected with isocortical areas, including sensory areas of the auditory, somatic and visual modalities, whereas the caudal non-isocortical sector is principally connected with non-isocortical areas, and, in the sensory domain, with olfactory and gustatory areas. The connections of the isocortical and non-isocortical orbital sectors with the amygdala, thalamus, striatum, hypothalamus and periaqueductal gray matter are also specific. The medial sector of the OfC is selectively connected with the hippocampus, posterior parahippocampal cortex, posterior cingulate and retrosplenial areas, and area prostriata, while the lateral orbitofrontal sector is the most heavily connected with sensory areas of the gustatory, somatic and visual modalities, with premotor regions, and with the amygdala.