Neural substrates of word category information as the basis of syntactic processing

The ability to use word category information (WCI) for syntactic structure building has been hypothesized to be the essence of human language faculty. The neural substrate of the ability of using the WCI for the complex syntactic hierarchical structure processing, however, is yet unknown. Therefore, we directly conducted an fMRI experiment by using a pseudo‐Chinese artificial language with syntactic structures containing a center‐embedded relative clause. Thirty non‐Chinese native (Korean) speakers were randomly divided into two groups: one acquired WCI and WCI‐based syntactic rules (the WCI group) before the scanning session, and the other did not (the non‐WCI group). Both groups were required to judge the grammaticality of the testing sentences, with critical long‐distance dependencies between two elements (the main verb and the relativizer). Behaviorally, the WCI group's accuracy was significantly higher and its reaction time was shorter. The scanning results showed that the left superior temporal gyrus (STG) and Broca's area were more strongly activated for the WCI group, and the dynamic causal modeling analyses revealed a distinct effective connectivity pattern for this group. Therefore, the present research, for the first time, reveals that the activation of and the functional connectivity between Broca's area and the left STG play a critical role in the ability of the rule‐based use of the WCI which is crucial for complex hierarchical structure building, and might be substantially corresponding to the “labeling competence” within the linguistic framework.     

Neural substrates of processing path and manner information of a moving event

Languages consistently distinguish the path and the manner of a moving event in different constituents, even if the specific constituents themselves vary across languages. Children also learn to categorize moving events according to their path and manner at different ages. Motivated by these linguistic and developmental observations, we employed fMRI to test the hypothesis that perception of and attention to path and manner of motion is segregated neurally. Moreover, we hypothesize that such segregation respects the "dorsal-where and ventral-what" organizational principle of vision. Consistent with this proposal, we found that attention to the path of a moving event was associated with greater activity within bilateral inferior/superior parietal lobules and the frontal eye-field, while attention to manner was associated with greater activity within bilateral postero-lateral inferior/middle temporal regions. Our data provide evidence that motion perception, traditionally considered as a dorsal "where" visual attribute, further segregates into dorsal path and ventral manner attributes. This neural segregation of the components of motion, which are linguistically tagged, points to a perceptual counterpart of the functional organization of concepts and language.     

Neural substrates of facial emotion processing using fMRI

We identified human brain regions involved in the perception of sad, frightened, happy, angry, and neutral facial expressions using functional magnetic resonance imaging (fMRI). Twenty-one healthy right-handed adult volunteers (11 men, 10 women; aged 18-45; mean age 21.6 years) participated in four separate runs, one for each of the four emotions. Participants viewed blocks of emotionally expressive faces alternating with blocks of neutral faces and scrambled images. In comparison with scrambled images, neutral faces activated the fusiform gyri, the right lateral occipital gyrus, the right superior temporal sulcus, the inferior frontal gyri, and the amygdala/entorhinal cortex. In comparisons of emotional and neutral faces, we found that (1) emotional faces elicit increased activation in a subset of cortical regions involved in neutral face processing and in areas not activated by neutral faces; (2) differences in activation as a function of emotion category were most evident in the frontal lobes; (3) men showed a differential neural response depending upon the emotion expressed but women did not.     

Neural processing of what and who information in speech

Human speech is composed of two types of information, related to content (lexical information, i.e., "what" is being said [e.g., words]) and to the speaker (indexical information, i.e., "who" is talking [e.g., voices]). The extent to which lexical versus indexical information is represented separately or integrally in the brain is unresolved. In the current experiment, we use short-term fMRI adaptation to address this issue. Participants performed a loudness judgment task during which single or multiple sets of words/pseudowords were repeated with single (repeat) or multiple talkers (speaker-change) conditions while BOLD responses were collected. As reflected by adaptation fMRI, the left posterior middle temporal gyrus, a crucial component of the ventral auditory stream performing sound-to-meaning computations ("what" pathway), showed sensitivity to lexical as well as indexical information. Previous studies have suggested that speaker information is abstracted during this stage of auditory word processing. Here, we demonstrate that indexical information is strongly coupled with word information. These findings are consistent with a plethora of behavioral results that have demonstrated that changes to speaker-related information can influence lexical processing.     

Neural substrates of olfactory processing in schizophrenia patients and their healthy relatives

Odorants represent powerful stimuli capable of eliciting various emotional responses. In schizophrenia patients and their non-affected relatives, olfactory and emotional functions are impaired, revealing a familial influence on these deficits. We aimed at determining the neural basis of emotional olfactory dysfunctions using odors of different emotional valence for mood induction and functional magnetic resonance imaging (fMRI) by comparing 13 schizophrenia patients, their non-affected brothers and 26 matched healthy controls. Blood-oxygen-level-dependent (BOLD) effects and subjective mood changes were assessed during negative (rotten yeast), positive (vanilla) and neutral (ambient air) olfactory stimulation. Group comparisons of brain activation were performed in regions of interest. Subjective ratings were comparable between groups and indicated successful mood induction. However, during stimulation with the negative odor, hypofunctional activity emerged in regions of the right frontal and temporal cortex in the patients. A familial influence in the neural substrates of negative olfactory dysfunction was indicated by a similar reduced frontal brain activity in relatives. Dysfunctions therefore appeared to be located in regions involved in higher cognitive processes associated with olfaction. No familial influences were indicated for cerebral dysfunctions during positive olfactory stimulation. Results point to a differentiation between trait and state components in cerebral dysfunctions during emotional olfactory processing in schizophrenia.     

Neural substrates differentiating global/local processing of bilateral visual inputs

We investigated neural substrates of global/local processing of bilateral hierarchical stimuli using functional magnetic resonance imaging (fMRI). Subjects were presented with two compound letters that were displayed simultaneously in the left and right visual fields, respectively. In a steady-state, block-design paradigm, hemodynamic responses were recorded while subjects detected infrequent global or local targets presented in one hemifield in separate epochs of trials. While behavioural responses were more accurate and faster to global than local targets, attention to the global level of bilateral visual inputs induced stronger activations in the left and right temporal cortex relative to attention to the local level. However, attention to the local level generated stronger activations in bilateral superior parietal cortex compared with attention to the global level. The results suggest that distinct neural substrates in the temporal and parietal cortices are preferentially engaged in the global and local processing of bilateral visual inputs, respectively.     

Dependence of carotid chemosensory responses on metabolic substrates.

The dependence of the carotid chemosensory response to hypoxia on metabolic substrate and the hypothesis that lactic acidosis is essential for O2 chemoreception were tested. Effects of 3 types of substrate (glucose, glutamate and a mixture of amino acids) on the response to hypoxia (perfusate flow interruption) were measured (n = 33 carotid bodies). The response to nicotine (n = 25) was used to determine whether these effects were exclusive to the hypoxic response. The cat carotid body was perfused and superfused in vitro with modified Tyrode solution (pO2 > 400 Torr, pCO2 < 1 Torr, pH = 7.4) at 36 degrees C containing a given substrate for at least 15 min prior to flow interruption or nicotine injection. Without substrate, responses to flow interruption (n = 4) and nicotine (n = 2) were irreversibly depressed. With glucose, responses to flow interruption (n = 13) and nicotine (n = 8) increased in a concentration-dependent fashion. Glutamate (42 mM) alone (n = 11) or a mixture of amino acids (4.2 mM) plus 5.5 mM glucose (n = 12) substituted for 11 mM glucose (n = 10). Thus, glutamate (42 mM), or a mixture of amino acids (4.2 mM) or a high concentration of glucose (11 mM) can support chemosensory responses to flow interruption and nicotine. Since glutamate undergoes oxidative deamination to alpha-ketoglutarate without lactic acid production, O2 chemoreception does not depend on lactic acidosis.     

Neural substrates of habit

Active reward pursuit is supported by the balance between the cognitive and habitual control of behavior. The cognitive, goal-directed strategy relies on the prospective evaluation of anticipated consequences, which allows behavior to readily adapt when circumstances change. Repetition of successful actions promotes less cognitively taxing habits, in which behavior is automatically executed without prospective consideration. Disruption in either of these behavioral regulatory systems contributes to the symptoms that underlie many psychiatric disorders. Here, I review recently identified neural substrates, at multiple neural levels, that contribute to habits and outline gaps in knowledge that must be addressed to fully understand the neural mechanisms of behavioral control.     

Neural substrates for serial reaction time tasks in pigeons

Most behavior is composed of action sequences. Pigeons were often used as a model to study sequence learning and execution. Yet, virtually nothing is known about the neural structures underlying sequential behavior in pigeons. We therefore applied a serial reaction time task (SRTT) that is commonly used to investigate sequential behavior. During task performance either the nidopallium caudolaterale (NCL) or the nidopallium intermedium medialis pars laterale (NIMl) was transiently inactivated with tetrodotoxin (TTX). Since prefrontal structures play a role in sequence acquisition and performance in mammals and since the NCL is functionally analogous to the prefrontal cortex, NCL was chosen a possibly critical structure of our study. The NIMl is equivalent by hodology and topology to the song nucleus LMAN. Since LMAN plays a key role in song learning and since song consists of learned vocalizatory sequences, we hypothesized that NIMl could also be a candidate for sequence performance in a non-songbird. Moreover, TTX injections into the entopallium were performed as a control. Indeed, inactivation of both the NCL and the NIMl resulted in an increase of sequence specific errors. Hence, we could identify components of neural systems in the pigeon that underlie sequence execution.     

Neural substrates for observing and imagining non-object-directed actions

The present fMRI study was aimed at assessing the cortical areas active when individuals observe non-object-directed actions (mimed, symbolic, and meaningless), and when they imagine performing those same actions. fMRI signal increases in common between action observation and motor imagery were found in the premotor cortex and in a large region of the inferior parietal lobule. While the premotor cortex activation overlapped that previously found during the observation and imagination of object-directed actions, in the parietal lobe the signal increase was not restricted to the intraparietal sulcus region, known to be active during the observation and imagination of object-directed actions, but extended into the supramarginal and angular gyri. When contrasting motor imagery with the observation of non-object-directed actions, signal increases were found in the mesial frontal and cingulate cortices, the supramarginal gyrus, and the inferior frontal gyrus. The opposite contrast showed activation virtually limited to visual areas. In conclusion, the present data define the common circuit for observing and imagining non-object-directed actions. In addition, they show that the representation of non-object-directed actions include parietal regions not found to be involved in coding object-directed actions.     

厌恶情绪加工神经机制的研究

目的探讨岛叶、基底节卒中患者的情绪认知特征,验证这些脑结构参与情绪加工以及厌恶的特异性神经机制的假说。方法测试2例岛叶损伤患者(例1、例2)、32例基底节卒中患者(基底节梗死或出血)和30名健康对照组的6种基本情绪(喜、惊、怕、悲、厌、怒)和中性情绪的面孔表情以及声音辨认能力。结果与相应对照组比较(厌恶面孔和厌恶声音的正确得分为14.65±2.25、17.61±3.12),例1、例2对厌恶声音和厌恶面孔的辨别均有障碍(厌恶面孔识别正确得分分别为7、9,厌恶声音识别正确得分分别为7、8,P<0.01)。而基底节卒中患者主要表现厌恶面孔辨别障碍(正确得分为10.42±2.71,P<0.01),对厌恶声音辨别正常,但表现为“怕”和“怒”的辨别障碍(正确得分为11.00±2.31、13.30±2.75,P<0.05)。结论基底节可能选择性参与厌恶情绪的视觉加工,而岛叶则选择性参与了厌恶情绪视觉和听觉通道的加工。岛叶-基底节系统在厌恶情绪加工中起着重要作用。     

Neural substrates of opiate reinforcement

1. 1. A major component of opiate reward is derived from a drug action in the ventral tegmental area: (a) rats quickly learn to self-administer morphine directly into the ventral tegmentum, (b) intracranial self-administration into other brain sites is not quickly learned, and (c) narcotic antagonist microinjections into the ventral tegmentum attenuate reward from intravenous heroin infusions.

2. 2. At least one component of opiate reward is dependent on a dopaminergic system: (a) electrophysiological and neurochemical indices suggest that opiates activate ventral tegmental dopaminergic neurons, (b) ventral tegmental opiate infusions are behaviorally activating producing contralateral rotation that is blocked by neuroleptics, (c) reward from heroin is blocked by neuroleptics, and (d) reward from heroin is attenuated by dopamine-depleting lesions of the ventral tegmental system.

3. 3. Brain sites involved in the production of physical dependence on opiates are anatomically distinct from those initiating the acutely rewarding action of opiates.

4. 4. It is theoretically viable that opiates derive their reinforcing impact from a combination of positive and negative reinforcement processes: (a) the neural substrate for the positive reinforcing action probably involves a ventral tegmental dopamine system important in appetitive motivation, and (b) the neural substrate for the negative reinforcing action may involve a periventricular gray system that is independent of the system which mediates the acutely rewarding property of opiates.

Neural substrates underlying intentional empathy

Although empathic responses to stimuli with emotional contents may occur automatically, humans are capable to intentionally empathize with other individuals. Intentional empathy for others is even possible when they do not show emotional expressions. However, little is known about the neuronal mechanisms of this intentionally controlled empathic process. To investigate the neuronal substrates underlying intentional empathy, we scanned 20 healthy Chinese subjects, using fMRI, when they tried to feel inside the emotional states of neutral or angry faces of familiar (Asian) and unfamiliar (Caucasian) models. Skin color evaluation of the same stimuli served as a control task. Compared to a baseline condition, the empathy task revealed a network of established empathy regions, including the anterior cingulate cortex, bilateral inferior frontal cortex and bilateral anterior insula. The contrast of intentional empathy vs skin color evaluation, however, revealed three regions: the bilateral inferior frontal cortex, whose hemodynamic responses were independent of perceived emotion and familiarity and the right-middle temporal gyrus, whose activity was modulated by emotion but not by familiarity. These findings extend our understanding of the role of the inferior frontal cortex and the middle temporal gyrus in empathy by demonstrating their involvement in intentional empathy.     

Neural substrates of numerosity estimation in autism

Visual skills, including numerosity estimation are reported to be superior in autism spectrum disorders (ASD). This phenomenon is attributed to individuals with ASD processing local features, rather than the Gestalt. We examined the neural correlates of numerosity estimation in adults with and without ASD, to disentangle perceptual atypicalities from numerosity processing. Fourteen adults with ASD and matched typically developed (TD) controls estimated the number of dots (80–150) arranged either randomly (local information) or in meaningful patterns (global information) while brain activity was recorded with magnetoencephalography (MEG). Behavioral results showed no significant group difference in the errors of estimation. However, numerical estimation in ASD was more variable across numerosities than TD and was not affected by the global arrangement of the dots. At 80–120 ms, MEG analyses revealed early significant differences (TD > ASD) in source amplitudes in visual areas, followed from 120 to 400 ms by group differences in temporal, and then parietal regions. After 400 ms, a source was found in the superior frontal gyrus in TD only. Activation in temporal areas was differently sensitive to the global arrangement of dots in TD and ASD. MEG data show that individuals with autism exhibit widespread functional abnormalities. Differences in temporal regions could be linked to atypical global perception. Occipital followed by parietal and frontal differences might be driven by abnormalities in the processing and conversion of visual input into a number‐selective neural code and complex cognitive decisional stages. These results suggest overlapping atypicalities in sensory, perceptual and number‐related processing during numerosity estimation in ASD. Hum Brain Mapp 35:4362–4385, 2014. © 2014 Wiley Periodicals, Inc .     

Neural substrates of opiate withdrawal.

Drug withdrawal is an integral part of most types of dependence and, to a large extent, opiate withdrawal has been considered the prototypic, classic measure of opiate dependence. The opiate withdrawal syndrome is characterized by multiple behavioral and physiological signs such as behavioral activation, ptosis, diarrhea, 'wet dog' shakes and motivational dysfunction, which may be represented in the CNS at multiple sites. It seems that the activating effects associated with the opiate withdrawal syndrome may be mediated by the nucleus locus coeruleus. Other signs such as wet dog shakes may involve sites in the hypothalamus important for temperature regulation. Certain other signs such as diarrhea and lacrimation may be dependent on peripheral opiate receptors. The motivational aspects of opiate withdrawal as demonstrated by the aversive stimulus effects or negative reinforcing effects (e.g. disrupted lever-pressing for food and place aversions) may involve those elements of the nucleus accumbens that are known to be important for the acute reinforcing effects of opiates in nondependent rats. Evidence exists at the cellular and molecular level for both 'within-system' and 'between-system' adaptations to dependence. Elucidation of the neural networks, cellular mechanisms and molecular elements involved in opiate withdrawal may provide not only a model for our understanding of the adaptive processes associated with drug dependence but also of those associated with other chronic insults to CNS function.     

Neural substrates of dynamic object occlusion

In everyday environments, objects frequently go out of sight as they move and our view of them becomes obstructed by nearer objects, yet we perceive these objects as continuous and enduring entities. Here, we used functional magnetic resonance imaging with an attentive tracking paradigm to clarify the nature of perceptual and cognitive mechanisms subserving this ability to fill in the gaps in perception of dynamic object occlusion. Imaging data revealed distinct regions of cortex showing increased activity during periods of occlusion relative to full visibility. These regions may support active maintenance of a representation of the target's spatiotemporal properties ensuring that the object is perceived as a persisting entity when occluded. Our findings may shed light on the neural substrates involved in object tracking that give rise to the phenomenon of object permanence.     

Neural substrates of action event knowledge

Human concepts can be roughly divided into entities (prototypically referred to in language by nouns) and events (prototypically referred to in language by verbs). While much work in cognitive neuroscience has investigated how the brain represents different categories of entities, less attention has been given to the more basic distinction between entities and events. We used functional magnetic resonance imaging to examine brain activity while subjects performed a conceptual matching task that required them to access knowledge of objects and actions, using either pictures or words. Since action events involve movement through space, we hypothesized that accessing knowledge of actions would cause greater activation in brain regions involved in motion or spatial processing. In comparison to objects, accessing knowledge of actions through pictures was accompanied by increased activity bilaterally in the human MT/MST and nearby regions of the lateral temporal cortex. Accessing knowledge of actions through words activated areas just anterior and dorsal to area MT/MST on the left, within the posterior aspect of the middle and superior temporal gyri. We propose that the lateral occipital-temporal cortex contains a mosaic of neural regions that processes different kinds of motion, ranging from the perception of objects moving in the world to the conception of movement implied in action verbs. The lateral occipital-temporal cortex mediates the perceptual and conceptual features of action events, similar to the way that the ventral occipital-temporal cortex processes the perceptual and conceptual features of entities.