Effects of TMS on Different Stages of Motor and Non-Motor Verb Processing in the Primary Motor Cortex

The embodied cognition hypothesis suggests that motor and premotor areas are automatically and necessarily involved in understanding action language, as word conceptual representations are embodied. This transcranial magnetic stimulation (TMS) study explores the role of the left primary motor cortex in action-verb processing. TMS-induced motor-evoked potentials from right-hand muscles were recorded as a measure of M1 activity, while participants were asked either to judge explicitly whether a verb was action-related (semantic task) or to decide on the number of syllables in a verb (syllabic task). TMS was applied in three different experiments at 170, 350 and 500 ms post-stimulus during both tasks to identify when the enhancement of M1 activity occurred during word processing. The delays between stimulus onset and magnetic stimulation were consistent with electrophysiological studies, suggesting that word recognition can be differentiated into early (within 200 ms) and late (within 400 ms) lexical-semantic stages, and post-conceptual stages. Reaction times and accuracy were recorded to measure the extent to which the participants' linguistic performance was affected by the interference of TMS with M1 activity. No enhancement of M1 activity specific for action verbs was found at 170 and 350 ms post-stimulus, when lexical-semantic processes are presumed to occur (Experiments 1–2). When TMS was applied at 500 ms post-stimulus (Experiment 3), processing action verbs, compared with non-action verbs, increased the M1-activity in the semantic task and decreased it in the syllabic task. This effect was specific for hand-action verbs and was not observed for action-verbs related to other body parts. Neither accuracy nor RTs were affected by TMS. These findings suggest that the lexical-semantic processing of action verbs does not automatically activate the M1. This area seems to be rather involved in post-conceptual processing that follows the retrieval of motor representations, its activity being modulated (facilitated or inhibited), in a top-down manner, by the specific demand of the task

Associative Vocabulary Learning: Development and Testing of Two Paradigms for the (Re-) Acquisition of Action- and Object-Related Words

Despite a growing number of studies, the neurophysiology of adult vocabulary acquisition is still poorly understood. One reason is that paradigms that can easily be combined with neuroscientfic methods are rare. Here, we tested the efficiency of two paradigms for vocabulary (re-) acquisition, and compared the learning of novel words for actions and objects. Cortical networks involved in adult native-language word processing are widespread, with differences postulated between words for objects and actions. Words and what they stand for are supposed to be grounded in perceptual and sensorimotor brain circuits depending on their meaning. If there are specific brain representations for different word categories, we hypothesized behavioural differences in the learning of action-related and object-related words. Paradigm A, with the learning of novel words for body-related actions spread out over a number of days, revealed fast learning of these new action words, and stable retention up to 4 weeks after training. The single-session Paradigm B employed objects and actions. Performance during acquisition did not differ between action-related and object-related words (time*word category: p = 0.01), but the translation rate was clearly better for object-related (79%) than for action-related words (53%, p = 0.002). Both paradigms yielded robust associative learning of novel action-related words, as previously demonstrated for object-related words. Translation success differed for action- and object-related words, which may indicate different neural mechanisms. The paradigms tested here are well suited to investigate such differences with neuroscientific means. Given the stable retention and minimal requirements for conscious effort, these learning paradigms are promising for vocabulary re-learning in brain-lesioned people. In combination with neuroimaging, neuro-stimulation or pharmacological intervention, they may well advance the understanding of language learning to optimize therapeutic strategies

Bi-Directional Effect of Cholecystokinin Receptor-2 Overexpression on Stress-Triggered Fear Memory and Anxiety in the Mouse

Fear, an emotional response of animals to environmental stress/threats, plays an important role in initiating and driving adaptive response, by which the homeostasis in the body is maintained. Overwhelming/uncontrollable fear, however, represents a core symptom of anxiety disorders, and may disturb the homeostasis. Because to recall or imagine certain cue(s) of stress/threats is a compulsory inducer for the expression of anxiety, it is generally believed that the pathogenesis of anxiety is associated with higher attention (acquisition) selectively to stress or mal-enhanced fear memory, despite that the actual relationship between fear memory and anxiety is not yet really established. In this study, inducible forebrain-specific cholecystokinin receptor-2 transgenic (IF-CCKR-2 tg) mice, different stress paradigms, batteries of behavioral tests, and biochemical assays were used to evaluate how different CCKergic activities drive fear behavior and hormonal reaction in response to stresses with different intensities. We found that in IF-CCKR-2 tg mice, contextual fear was impaired following 1 trial of footshock, while overall fear behavior was enhanced following 36 trials of footshock, compared to their littermate controls. In contrast to a standard Yerkes-Dodson (inverted-U shaped) stress-fear relationship in control mice, a linearized stress-fear curve was observed in CCKR-2 tg mice following gradient stresses. Moreover, compared to 1 trial, 36 trials of footshock in these transgenic mice enhanced anxiety-like behavior in other behavioral tests, impaired spatial and recognition memories, and prolonged the activation of adrenocorticotropic hormone (ACTH) and glucocorticoids (CORT) following new acute stress. Taken together, these results indicate that stress may trigger two distinctive neurobehavioral systems, depending on both of the intensity of stress and the CCKergic tone in the brain. A “threshold theory” for this two-behavior system has been suggested

Adenosine A1 receptor: Functional receptor-receptor interactions in the brain

Over the past decade, many lines of investigation have shown that receptor-mediated signaling exhibits greater diversity than previously appreciated. Signal diversity arises from numerous factors, which include the formation of receptor dimers and interplay between different receptors. Using adenosine A1 receptors as a paradigm of G protein-coupled receptors, this review focuses on how receptor-receptor interactions may contribute to regulation of the synaptic transmission within the central nervous system. The interactions with metabotropic dopamine, adenosine A2A, A3, neuropeptide Y, and purinergic P2Y1 receptors will be described in the first part. The second part deals with interactions between A1Rs and ionotropic receptors, especially GABAA, NMDA, and P2X receptors as well as ATP-sensitive K+ channels. Finally, the review will discuss new approaches towards treating neurological disorders