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.     

基于视觉搜索的外源易化和返回抑制脑机制研究

采用事件相关电位技术研究了在视觉搜索过程中的外源易化和返回抑制（inhibition of return,IOR）的相互关系。当外源注意保持在序列搜索过的位置上时,有一个延时反应(即IOR）,伴随其产生的相关脑电成分有：分布在后顶的潜伏期为200 ms 的正差异、分布在前额叶内侧靠左的潜伏期为240 毫秒的负差异,以及分布在两侧颞顶联合区的潜伏期为280 ms 的负差异。而当外源注意保持在平行搜索的位置上时,则出现了明显的易化效应,伴随其产生的脑电成分仅为分布在枕顶区域的潜伏期为280 ms 的负差异。这些结果表明,外源易化和IOR 涉及了不同的脑区和神经过程,从而支持两者在机制上是可分离性的观点。     

Dissociable influences of auditory object vs. spatial attention on visual system oscillatory activity

Given that both auditory and visual systems have anatomically separate object identification ("what") and spatial ("where") pathways, it is of interest whether attention-driven cross-sensory modulations occur separately within these feature domains. Here, we investigated how auditory "what" vs. "where" attention tasks modulate activity in visual pathways using cortically constrained source estimates of magnetoencephalograpic (MEG) oscillatory activity. In the absence of visual stimuli or tasks, subjects were presented with a sequence of auditory-stimulus pairs and instructed to selectively attend to phonetic ("what") vs. spatial ("where") aspects of these sounds, or to listen passively. To investigate sustained modulatory effects, oscillatory power was estimated from time periods between sound-pair presentations. In comparison to attention to sound locations, phonetic auditory attention was associated with stronger alpha (7-13 Hz) power in several visual areas (primary visual cortex; lingual, fusiform, and inferior temporal gyri, lateral occipital cortex), as well as in higher-order visual/multisensory areas including lateral/medial parietal and retrosplenial cortices. Region-of-interest (ROI) analyses of dynamic changes, from which the sustained effects had been removed, suggested further power increases during Attend Phoneme vs. Location centered at the alpha range 400-600 ms after the onset of second sound of each stimulus pair. These results suggest distinct modulations of visual system oscillatory activity during auditory attention to sound object identity ("what") vs. sound location ("where"). The alpha modulations could be interpreted to reflect enhanced crossmodal inhibition of feature-specific visual pathways and adjacent audiovisual association areas during "what" vs. "where" auditory attention.     

Electrophysiological correlates of strategic monitoring in event-based and time-based prospective memory

Prospective memory (PM) is the ability to remember to accomplish an action when a particular event occurs (i.e., event-based PM), or at a specific time (i.e., time-based PM) while performing an ongoing activity. Strategic Monitoring is one of the basic cognitive functions supporting PM tasks, and involves two mechanisms: a retrieval mode, which consists of maintaining active the intention in memory; and target checking, engaged for verifying the presence of the PM cue in the environment. The present study is aimed at providing the first evidence of event-related potentials (ERPs) associated with time-based PM, and at examining differences and commonalities in the ERPs related to Strategic Monitoring mechanisms between event- and time-based PM tasks.The addition of an event-based or a time-based PM task to an ongoing activity led to a similar sustained positive modulation of the ERPs in the ongoing trials, mainly expressed over prefrontal and frontal regions. This modulation might index the retrieval mode mechanism, similarly engaged in the two PM tasks. On the other hand, two further ERP modulations were shown specifically in an event-based PM task. An increased positivity was shown at 400-600 ms post-stimulus over occipital and parietal regions, and might be related to target checking. Moreover, an early modulation at 130-180 ms post-stimulus seems to reflect the recruitment of attentional resources for being ready to respond to the event-based PM cue. This latter modulation suggests the existence of a third mechanism specific for the event-based PM; that is, the "readiness mode".     

Task-specific impairments and enhancements induced by magnetic stimulation of human visual area V5.

Transcranial magnetic stimulation (TMS) can be used to simulate the effects of highly circumscribed brain damage permanently present in some neuropsychological patients, by reversibly disrupting the normal functioning of the cortical area to which it is applied. By using TMS we attempted to recreate deficits similar to those reported in a motion-blind patient and to assess the specificity of deficits when TMS is applied over human area V5. We used six visual search tasks and showed that subjects were impaired in a motion but not a form ''pop-out'' task when TMS was applied over V5. When motion was present, but irrelevant, or when attention to colour and form were required, TMS applied to V5 enhanced performance. When attention to motion was required in a motion-form conjunction search task, irrespective of whether the target was moving or stationary, TMS disrupted performance. These data suggest that attention to different visual attributes involves mutual inhibition between different extrastriate visual areas.     

Attentional Requirements on Feature Search Are Modulated by Stimulus Properties

We report a series of dual-task experiments, in which a rapid serial visual presentation (RSVP) task was combined with a visual search task. Orientation, motion, and color were used as the defining target features in the search task. Lag between target onsets was manipulated and interference between the two tasks was quantified by measuring detection scores for the search task as a function of lag. While simultaneous performance of an orientation detection task with an RSVP letter identification task resulted in a performance decrease for lags up to 320 ms, no such decrease was detected for highly salient motion- and color-defined targets. Subsequently, detectability of the motion and color feature was matched to that of the orientation-feature resulting in the reintroduction of a (smaller) performance decrease, but only during simultaneous performance (lag 0 ms). The results suggest that there are two causes for the impaired search performance occurring when a feature search task is combined with an RSVP task. The first is short-lasting interference probably due to attentional competition; the second, which plays a role only when targets for both tasks share features, is interference that may be attributed to a central processing bottleneck.     

Single-trial classification of parallel pre-attentive and serial attentive processes using functional magnetic resonance imaging

Theories of perception have proposed a basic distinction between parallel pre-attentive and serial attentive modes of processing. However, chronometric measures are often ambiguous in separating parallel and serial processes. We have used the activity of attention-related regions of the human brain, measured with functional magnetic resonance imaging, to separate parallel from serial processes at the single-trial level in a visual quantification task. In this task, some have suggested the deployment of two qualitatively different processes, a fast parallel 'subitizing' for sets of one, two or three objects and a slow serial counting for larger sets. Our results indicate that attention-related regions of the posterior parietal and frontal cortices show a sudden increase in activity only from numerosity four onwards, confirming the parallel-serial dichotomy of subitizing and counting. Moreover, using the presence or absence of attentional shifts, as inferred from the activation of posterior parietal regions, we successfully predict whether, on a given trial, subjects deployed a serial exploration of the display or a parallel apprehension. Beyond the subitizing/counting debate, this approach may prove useful to probe the attentional demands of other cognitive tasks.     

The Brain's Router: A Cortical Network Model of Serial Processing in the Primate Brain

The human brain efficiently solves certain operations such as object recognition and categorization through a massively parallel network of dedicated processors. However, human cognition also relies on the ability to perform an arbitrarily large set of tasks by flexibly recombining different processors into a novel chain. This flexibility comes at the cost of a severe slowing down and a seriality of operations (100–500 ms per step). A limit on parallel processing is demonstrated in experimental setups such as the psychological refractory period (PRP) and the attentional blink (AB) in which the processing of an element either significantly delays (PRP) or impedes conscious access (AB) of a second, rapidly presented element. Here we present a spiking-neuron implementation of a cognitive architecture where a large number of local parallel processors assemble together to produce goal-driven behavior. The precise mapping of incoming sensory stimuli onto motor representations relies on a “router” network capable of flexibly interconnecting processors and rapidly changing its configuration from one task to another. Simulations show that, when presented with dual-task stimuli, the network exhibits parallel processing at peripheral sensory levels, a memory buffer capable of keeping the result of sensory processing on hold, and a slow serial performance at the router stage, resulting in a performance bottleneck. The network captures the detailed dynamics of human behavior during dual-task-performance, including both mean RTs and RT distributions, and establishes concrete predictions on neuronal dynamics during dual-task experiments in humans and non-human primates.     

Task-dependent interaction between parietal and contralateral primary motor cortex during explicit versus implicit motor imagery

Both mental rotation (MR) and motor imagery (MI) involve an internalization of movement within motor and parietal cortex. Transcranial magnetic stimulation (TMS) techniques allow for a task-dependent investigation of the interhemispheric interaction between these areas. We used image-guided dual-coil TMS to investigate interactions between right inferior parietal lobe (rIPL) and left primary motor cortex (M1) in 11 healthy participants. They performed MI (right index-thumb pinching in time with a 1 Hz metronome) or hand MR tasks, while motor evoked potentials (MEPs) were recorded from right first dorsal interosseous. At rest, rIPL conditioning 6 ms prior to M1 stimulation facilitated MEPs in all participants, whereas this facilitation was abolished during MR. While rIPL conditioning 12 ms prior to M1 stimulation had no effect on MEPs at rest, it suppressed corticomotor excitability during MI. These results support the idea that rIPL forms part of a distinct inhibitory network that may prevent unwanted movement during imagery tasks.     

Paired associative stimulation of the auditory system: a proof-of-principle study

Background

Paired associative stimulation (PAS) consisting of repeated application of transcranial magnetic stimulation (TMS) pulses and contingent exteroceptive stimuli has been shown to induce neuroplastic effects in the motor and somatosensory system. The objective was to investigate whether the auditory system can be modulated by PAS.

Methods

Acoustic stimuli (4 kHz) were paired with TMS of the auditory cortex with intervals of either 45 ms (PAS(45 ms)) or 10 ms (PAS(10 ms)). Two-hundred paired stimuli were applied at 0.1 Hz and effects were compared with low frequency repetitive TMS (rTMS) at 0.1 Hz (200 stimuli) and 1 Hz (1000 stimuli) in eleven healthy students. Auditory cortex excitability was measured before and after the interventions by long latency auditory evoked potentials (AEPs) for the tone (4 kHz) used in the pairing, and a control tone (1 kHz) in a within subjects design.

Results

Amplitudes of the N1-P2 complex were reduced for the 4 kHz tone after both PAS(45 ms) and PAS(10 ms), but not after the 0.1 Hz and 1 Hz rTMS protocols with more pronounced effects for PAS(45 ms). Similar, but less pronounced effects were observed for the 1 kHz control tone.

Conclusion

These findings indicate that paired associative stimulation may induce tonotopically specific and also tone unspecific human auditory cortex plasticity.     

Modality-specific control of strategic spatial attention in parietal cortex

The neural basis of selective spatial attention presents a significant challenge to cognitive neuroscience. Recent neuroimaging studies have suggested that regions of the parietal and temporal cortex constitute a "supramodal" network that mediates goal-directed attention in multiple sensory modalities. Here we used transcranial magnetic stimulation (TMS) to determine which cortical subregions control strategic attention in vision and touch. Healthy observers undertook an orienting task in which a central arrow cue predicted the location of a subsequent visual or somatosensory target. To determine the attentional role of cortical subregions at different stages of processing, TMS was delivered to the right hemisphere during cue or target events. Results indicated a critical role of the inferior parietal cortex in strategic orienting to visual events, but not to somatosensory events. These findings are inconsistent with the existence of a supramodal attentional network and instead provide direct evidence for modality-specific attentional processing in parietal cortex.     

Perceiving what is reachable depends on motor representations: evidence from a transcranial magnetic stimulation study

Background

Visually determining what is reachable in peripersonal space requires information about the egocentric location of objects but also information about the possibilities of action with the body, which are context dependent. The aim of the present study was to test the role of motor representations in the visual perception of peripersonal space.

Methodology

Seven healthy participants underwent a TMS study while performing a right-left decision (control) task or perceptually judging whether a visual target was reachable or not with their right hand. An actual grasping movement task was also included. Single pulse TMS was delivered 80% of the trials on the left motor and premotor cortex and on a control site (the temporo-occipital area), at 90% of the resting motor threshold and at different SOA conditions (50ms, 100ms, 200ms or 300ms).

Principal Findings

Results showed a facilitation effect of the TMS on reaction times in all tasks, whatever the site stimulated and until 200ms after stimulus presentation. However, the facilitation effect was on average 34ms lower when stimulating the motor cortex in the perceptual judgement task, especially for stimuli located at the boundary of peripersonal space.

Conclusion

This study provides the first evidence that brain motor area participate in the visual determination of what is reachable. We discuss how motor representations may feed the perceptual system with information about possible interactions with nearby objects and thus may contribute to the perception of the boundary of peripersonal space.     

Attention modulates earliest responses in the primary auditory and visual cortices

A fundamental question about the neural correlates of attention concerns the earliest sensory processing stage that it can affect. We addressed this issue by recording magnetoencephalography (MEG) signals while subjects performed detection tasks, which required employment of spatial or nonspatial attention, in auditory or visual modality. Using distributed source analysis of MEG signals, we found that, contrary to previous studies that used equivalent current dipole (ECD) analysis, spatial attention enhanced the initial feedforward response in the primary visual cortex (V1) at 55-90 ms. We also found attentional modulation of the putative primary auditory cortex (A1) activity at 30-50 ms. Furthermore, we reproduced our findings using ECD modeling guided by the results of distributed source analysis and suggest a reason why earlier studies using ECD analysis failed to identify the modulation of earliest V1 activity.     

Exploring BOLD Changes during Spatial Attention in Non-Stimulated Visual Cortex

Blood oxygen level-dependent (BOLD) responses were measured in parts of primary visual cortex that represented unstimulated visual field regions at different distances from a stimulated central target location. The composition of the visual scene varied by the presence or absence of additional peripheral distracter stimuli. Bottom-up effects were assessed by comparing peripheral activity during central stimulation vs. no stimulation. Top-down effects were assessed by comparing active vs. passive conditions. In passive conditions subjects simply watched the central letter stimuli and in active conditions they had to report occurrence of pre-defined targets in a rapid serial letter stream. Onset of the central letter stream enhanced activity in V1 representations of the stimulated region. Within representations of the periphery activation decreased and finally turned into deactivation with increasing distance from the stimulated location. This pattern was most pronounced in the active conditions and during the presence of peripheral stimuli. Active search for a target did not lead to additional enhancement at areas representing the attentional focus but to a stronger deactivation in the vicinity. Suppressed neuronal activity was also found in the non distracter condition suggesting a top-down attention driven effect. Our observations suggest that BOLD signal decreases in primary visual cortex are modulated by bottom-up sensory-driven factors such as the presence of distracters in the visual field as well as by top-down attentional processes.     

Task Type Affects Location of Language-Positive Cortical Regions by Repetitive Navigated Transcranial Magnetic Stimulation Mapping

Objectives

Recent repetitive TMS (rTMS) mapping protocols for language mapping revealed deficits of this method, mainly in posterior brain regions. Therefore this study analyzed the impact of different language tasks on the localization of language-positive brain regions and compared their effectiveness, especially with regard to posterior brain regions.

Methods

Nineteen healthy, right-handed subjects performed object naming, pseudoword reading, verb generation, and action naming during rTMS language mapping of the left hemisphere. Synchronically, 5 Hz/10 pulses were applied with a 0 ms delay

Results

The object naming task evoked the highest error rate (14%), followed by verb generation (13%) and action naming (11%). The latter revealed more errors in posterior than in anterior areas. Pseudoword reading barely generated errors, except for phonological paraphasias.

Conclusions

In general, among the evaluated language tasks, object naming is the most discriminative task to detect language-positive regions via rTMS. However, other tasks might be used for more specific questions.     

Fast noninertial shifts of attention

It was suggested that some discrimination tasks (e.g. discrimination between the letters T and L) require serial search by scrutinizing each letter (target) with a small aperture of focal attention. Here we examine the effect of intertarget distance on discrimination performance, using two targets. We find reduction in performance at short distances, in agreement with masking studies, but constant performance independent of distance outside this masking region. This constant performance is still lower than expected from masking effects and might reflect attentive process. Sequential presentation of the targets with delays up to 30-40 ms, while reducing available processing time, does not cause reduction in performance, thus supporting the suggestion that discrimination of the two targets is a serial process. The independence of performance on distance suggests fast noninertial shifts of attention.     

Visual attention: spotlight on the primary visual cortex.

Visual search tasks appear to involve spatially selective attention to the target, but evidence for attentional modulation in the visual area with the most precise retinotopic organization V1 has been elusive. Recent imaging studies show that spatial attention can indeed enhance visual responses in human V1.     

Development of working memory brain organization in young schoolchildren

In children of 7-8 and 9-10 years old, the ERP components were studied by comparing two non-verbalized visuo-spatial stimuli shown in succession with 1.5-1.8 s interstimulus interval. We found the age-related differences in the specific way (and the extent to which) the cortical areas were involved into the processes of the reference stimulus (the first stimulus in the pair) encoding and into the process of comparing the memory trace against the test stimulus. In both age groups, the sensory-specific N1 ERP component in the visual cortices had larger amplitude during working memory than during free observation. Age-related differences in the processing of the sensory-specific parameters of a stimulus are most pronounced in ERP to the test stimulus: in children of 9-10, the amplitude of N1 component increased significantly in all caudal leads following the earlier increase in P1 component in the inferior temporal and occipital areas. In the children of that age, unlike children of 7-8, the early involvement of ventro-lateral prefrontal cortex becomes apparent. In that area an increase of positivity confined to 100-200 ms post-stimulus is observed. Substantial inter-group differences are observed in the late ERP components that are related to cognitive operations. In children of 7-8, presenting both reference and test stimuli causes a significant increase in the amplitude of late positive complex (LPC) in caudal leads with maximal increase being observed in parietal areas at 300-800 ms post-stimulus. In children of 9-10, one can see some adult-like features of the late ERP components during different stages of the working memory process: in fronto-central areas N400 component increases in response to the reference stimulus, whereas LPC increases in response to the test stimulus. The data reported in this work show that the almost mature functional organization of working memory is already in place at the age of 9-10. However, the extent of the prefrontal cortex (especially its dorsal areas) involvement does not yet match the level of maturity.     

No evidence for early modulation of evoked responses in primary visual cortex to irrelevant probe stimuli presented during the attentional blink

Background

During rapid serial visual presentation (RSVP), observers often miss the second of two targets if it appears within 500 ms of the first. This phenomenon, called the attentional blink (AB), is widely held to reflect a bottleneck in the processing of rapidly sequential stimuli that arises after initial sensory registration is complete (i.e., at a relatively late, post-perceptual stage of processing). Contrary to this view, recent fMRI studies have found that activity in the primary visual area (V1), which represents the earliest cortical stage of visual processing, is attenuated during the AB. Here we asked whether such changes in V1 activity during the AB arise in the initial feedforward sweep of stimulus input, or instead reflect the influence of feedback signals from higher cortical areas.

Methodology/Principal Findings

EEG signals were recorded while participants monitored a sequential stream of distractor letters for two target digits (T1 and T2). Neural responses associated with an irrelevant probe stimulus presented simultaneously with T2 were measured using an ERP marker – the C1 component – that reflects initial perceptual processing of visual information in V1. As expected, T2 accuracy was compromised when the inter-target interval was brief, reflecting an AB deficit. Critically, however, the magnitude of the early C1 component evoked by the probe was not reduced during the AB.

Conclusions/Significance

Our finding that early sensory processing of irrelevant probe stimuli is not suppressed during the AB is consistent with theoretical models that assume that the bottleneck underlying the AB arises at a post-perceptual stage of processing. This suggests that reduced neural activity in V1 during the AB is driven by re-entrant signals from extrastriate areas that regulate early cortical activity via feedback connections with V1.     

Characterization of visual percepts evoked by noninvasive stimulation of the human posterior parietal cortex

Phosphenes are commonly evoked by transcranial magnetic stimulation (TMS) to study the functional organization, connectivity, and excitability of the human visual brain. For years, phosphenes have been documented only from stimulating early visual areas (V1-V3) and a handful of specialized visual regions (V4, V5/MT+) in occipital cortex. Recently, phosphenes were reported after applying TMS to a region of posterior parietal cortex involved in the top-down modulation of visuo-spatial processing. In the present study, we systematically characterized parietal phosphenes to determine if they are generated directly by local mechanisms or emerge through indirect activation of other visual areas. Using technology developed in-house to record the subjective features of phosphenes, we found no systematic differences in the size, shape, location, or frame-of-reference of parietal phosphenes when compared to their occipital counterparts. In a second experiment, discrete deactivation by 1 Hz repetitive TMS yielded a double dissociation: phosphene thresholds increased at the deactivated site without producing a corresponding change at the non-deactivated location. Overall, the commonalities of parietal and occipital phosphenes, and our ability to independently modulate their excitability thresholds, lead us to conclude that they share a common neural basis that is separate from either of the stimulated regions.