Paired pulse TMS over the right posterior parietal cortex modulates visuospatial perception

OBJECTIVE: We previously observed a relative contralateral neglect by right parietal single-pulse TMS given 150 ms after visual stimulus presentation. Here we investigated the effects of parietal paired TMS in normal subjects performing a visuospatial task. METHODS: Thirteen right-handed healthy subjects underwent a line-length judgement task during single-pulse and paired (1, 3, 5, 10 ms ISIs) TMS, delivered on the right parietal cortex 150 ms after visual stimulus. RESULTS: Single pulse TMS over the right parietal cortex induced a significant rightward bias compared to the baseline condition. At 1 and 3 ms ISIs, paired-pulse TMS did not show any effect in comparison with single pulse TMS. More importantly, 5 ms ISI was able to restore baseline levels, thus inducing a significant improvement of the performance compared to single-pulse TMS and 1-3 ms ISIs. CONCLUSIONS: Paired TMS seems able to modulate activity of the right posterior parietal cortex in healthy subjects performing a cognitive visuospatial task.     

Hemispheric asymmetry in cortical control of memory-guided saccades. A transcranial magnetic stimulation study

To study the temporal organisation of memory-guided saccade control we used single-pulse transcranial magnetic stimulation (TMS) over the left posterior parietal (PPC) and prefrontal cortex (PFC) in eight healthy subjects. TMS was applied either following presentation of a visual target, i.e. 160, 260, and 360 ms after the flashed point, or during the period of memorisation, i.e. between 700 and 1500 ms, or finally 100 ms after extinguishing of the central fixation point (i.e. 2100 ms after the target presentation). Latency of memory-guided saccades and the percentage of error in amplitude (PEA) was measured and compared with results without stimulation.TMS over the left PPC 100 ms after the extinguishing of the central fixation point significantly increased memory-guided saccade latency bilaterally. Furthermore, stimulation over the left PFC had a significant effect on the PEA of contralateral memory-guided saccades when applied during the period of memorisation, i.e. between 700 and 1500 ms.In a previous study using identical methodology [13: Müri RM, Vermersch SI, Rivaud S, Gaymard B, Pierrot-Deseilligny C. Effects of single-pulse transcranial magnetic stimulation over the prefrontal and posterior parietal cortices during memory-guided saccades in humans. Journal of Neurophysiology 1996;76:2102-2106], we found that TMS over the right PPC increased the contralateral PEA when applied 260 ms after the flash, the effects on saccade latency after right PPC stimulation or on the PEA after right PFC stimulation being similar to those observed here. Taken together, these results show that (1) a hemispheric asymmetry in the preparation of memory-guided saccade amplitude during the early phase of sensorimotor integration exists, (2) memory-guided saccade triggering is controlled by PPC on both sides, and (3) PFC on both sides are involved in spatial working memory performance.     

Posterior parietal cortex mediates encoding and maintenance processes in change blindness

It is commonly accepted that right posterior parietal cortex (PPC) plays an important role in updating spatial representations, directing visuospatial attention, and planning actions. However, recent studies suggest that right PPC may also be involved in processes that are more closely associated with our visual awareness as its activation level positively correlates with successful conscious change detection (Beck, D.M., Rees, G., Frith, C.D., & Lavie, N. (2001). Neural correlates of change detection and change blindness. Nature Neuroscience, 4, 645-650.). Furthermore, disruption of its activity increases the occurrences of change blindness, thus suggesting a causal role for right PPC in change detection (Beck, D.M., Muggleton, N., Walsh, V., & Lavie, N. (2006). Right parietal cortex plays a critical role in change blindness. Cerebral Cortex, 16, 712-717.). In the context of a 1-shot change detection paradigm, we applied transcranial magnetic stimulation (TMS) during different time intervals to elucidate the temporally precise involvement of PPC in change detection. While subjects attempted to detect changes between two image sets separated by a brief time interval, TMS was applied either during the presentation of picture 1 when subjects were encoding and maintaining information into visual short-term memory, or picture 2 when subjects were retrieving information relating to picture 1 and comparing it to picture 2. Our results show that change blindness occurred more often when TMS was applied during the viewing of picture 1, which implies that right PPC plays a crucial role in the processes of encoding and maintaining information in visual short-term memory. In addition, since our stimuli did not involve changes in spatial locations, our findings also support previous studies suggesting that PPC may be involved in the processes of encoding non-spatial visual information (Todd, J.J. & Marois, R. (2004). Capacity limit of visual short-term memory in human posterior parietal cortex. Nature, 428, 751-754.).     

Hemispheric lateralization of number comparison

In order to clarify the respective contribution of the right and left posterior parietal cortex (PPC) to number comparison, transcranial magnetic stimulation (TMS) was used to disrupt PPC processing in subjects instructed to determine whether a digit was smaller or larger than 5. Single pulse TMS was applied over the PPC, either unilaterally or bilaterally, 150, 200, or 250 ms after digit presentation. Sham TMS was used as a control condition to take into account the unspecific effects of TMS on reaction time (RT). The main finding of the present study is a significant increase in RTs when comparing digits close to 5 following a disruption either of the left PPC alone or of both PPC simultaneously. The comparison of digits far from 5 was unaltered by disrupting only one PPC but RTs were found increased after bilateral PPC stimulation. These disruptive effects were observed irrespective of the TMS delay. We concluded that coding precise numerical values requires the integrity of the left PPC, as suggested by the deficit in discriminating close digits consequent to its disruption. In contrast, approximate comparisons can be processed either by the left or right PPC, since simultaneous bilateral TMS was needed to alter the comparison of digits far from 5.     

Interhemispheric balance of overt attention: a theta burst stimulation study

Interhemispheric imbalance is discussed as a pathophysiological mechanism in visuospatial neglect. It is suggested that after a lesion of the right hemisphere the mutual transcallosal inhibition is impaired, resulting in an increased activity of the left hemisphere. We investigated the interhemispheric balance of attention in healthy subjects by using a free visual exploration task and by interfering with the neural activity of the posterior parietal cortex (PPC) of either hemisphere using an inhibitory transcranial magnetic stimulation routine with theta burst stimulation (TBS). Subjects explored colour photographs of real-life scenes presented on a computer screen under four conditions: (i) without TBS; (ii) after TBS over the right PPC; (iii) after TBS over the left PPC; and (iv) after TBS over the right PPC and, after the first half of the task, over the left PPC. Eye movements were measured, and distribution of mean cumulative fixation duration over screen halves was analyzed. TBS over the right PPC resulted in a significant rightward shift of mean cumulative fixation duration of ∼30 min. The shift could be reversed when a subsequent train of TBS was applied over the left PPC. However, left PPC stimulation alone had no significant effect on visual exploration behaviour. The present study shows that the effect of TBS on the PPC depends on which hemisphere is stimulated and on the state of the contralateral homologue area. These findings are in accordance with the predictions of the interhemispheric rivalry model in neglect.     

Differential effects of transcranial magnetic stimulation of left and right posterior parietal cortex on mental rotation tasks

A recently published study used the interference strategy of transcranial magnetic stimulation (TMS) to demonstrate the role of the right posterior parietal cortex (PPC) in the mental rotation of alphanumeric stimuli. We used similar stimulation parameters over the same left and right PPC regions, and examined the ability to rotate more complex 3D Shepard and Metzler (1971) images. There was reduced accuracy of performance with both right and left PPC stimulation for different angles of rotation of the visual stimuli. Right PPC stimulation led to reduced accuracy to rotate stimuli by 1200, whereas left PPC stimulation affected 180 degrees C rotation. We hypothesise that the two hemispheres make different contributions to the processing underlying visuospatial mental imagery: the right PPC is important for spatial rotations through smaller angles; the left hemisphere has a unique role when the stimuli to be compared are rotated through 180 degrees C, a task that engages verbal strategies due to the well-documented special nature of enantiomorphs.     

Parietal rTMS distorts the mental number line: simulating 'spatial' neglect in healthy subjects

Patients with left-sided visuospatial neglect, typically after damage to the right parietal lobe, show a systematic bias towards larger numbers when asked to bisect a numerical interval. This has been taken as further evidence for a spatial representation of numbers, perhaps akin to a mental number line with smaller numbers represented to the left and larger numbers to the right. Previously, contralateral neglect-like symptoms in physical line bisection have been induced in healthy subjects with repetitive transcranial magnetic stimulation (rTMS) over right posterior parietal lobe. Here we used rTMS over parietal and occipital sites in healthy subjects to investigate spatial representations in a number bisection task. Subjects were asked to name the midpoint of numerical intervals without calculating. On control trials subjects' behaviour was similar to performance reported in physical line bisection experiments. Subjects underestimated the midpoint of the numerical interval. Repetitive transcranial magnetic stimulation produced representational neglect-like symptoms in number bisection when applied over right posterior parietal cortex (right PPC). Repetitive TMS over right PPC shifted the perceived midpoint of the numerical interval significantly to the right while occipital TMS had no effect on bisection performance. Our study therefore provides further evidence that subjects use spatial representations, perhaps akin to a mental number line, in basic numerical processing tasks. Furthermore, we showed that the right posterior parietal cortex is crucially involved in spatial representation of numbers.     

Network mechanisms of responsiveness to continuous theta‐burst stimulation

Continuous theta‐burst stimulation (cTBS) can modify behavior, but effects are inconsistent and their mechanisms insufficiently understood. As coherence in resting‐state networks influences human behavior, we hypothesized that cTBS may act via modulation of neural oscillation coherence. This study used electroencephalography (EEG) to investigate whether behavioral effects of cTBS on visuospatial attention are associated with coherence changes in the attention network. In healthy human subjects, cTBS of the right posterior parietal cortex (PPC) and the right frontal eye field was compared with sham stimulation. Effects on visuospatial attention were quantified with a visual exploration task, and network effects were assessed from surface EEG with inverse solutions and source coherence analyses. Before stimulation, left visual exploration was linearly correlated with alpha‐band coherence between the right temporo‐parietal cortex and the rest of the brain. Posterior parietal cortex stimulation induced neglect‐like visual exploration behavior in the majority, but not all, subjects. It reduced alpha‐band coherence between the stimulation site and the rest of the brain but also enhanced it between the contralateral left parietal cortex and the rest of the brain. The contralateral increase correlated with the induced reduction in left visual attention. The behavioral response of individual participants to cTBS could be predicted by coherence in the right temporo‐parietal junction before stimulation. Behavioral effects of cTBS therefore depend on network states before stimulation and are linearly associated with changes in network interactions. In particular, cTBS modulates an interhemispheric competition in alpha‐band coherence. EEG network imaging might help to optimize therapeutic cTBS in the future.     

The role of the left posterior parietal lobule in top-down modulation on space-based attention: a transcranial magnetic stimulation study

Converging evidence from neuroimaging as well as lesion and transcranial magnetic stimulation (TMS) studies has been obtained for the involvement of right ventral posterior parietal cortex (PPC) in exogenous orienting. However, the contribution of dorsal PPC to attentional orienting, particularly endogenous orienting, is still under debate. In an informative peripheral cueing paradigm, in which the exogenous and endogenous orienting can be studied in relative isolation within a single task, we applied TMS over sub-regions of dorsal PPC to explore their possible distinct involvement in exogenous and endogenous processes. We found that disruption of the left posterior intraparietal sulcus (pIPS) weakened the attentional effects of endogenous orienting, but did not affect exogenous processes. In addition, TMS applied over the right superior parietal lobule (SPL) resulted in an overall increase in reaction times. The present study provides the causal evidence that the left pIPS plays a crucial role in voluntary orienting of visual attention, while right SPL is involved in the processing of arousal and/or vigilance.     

Event-related TMS over the right posterior parietal cortex induces ipsilateral visuo-spatial interference

The right posterior parietal cortex (PPC) is implicated in visuo-spatial processing, as illustrated by patients with visuo-spatial neglect, but the precise time-course of its contribution is still an open question. In the present study we assessed whether single-pulse transcranial magnetic stimulation (TMS) can interfere with the performance of normal subjects in a standard visuo-spatial task. Participants had to perform a landmark task while TMS was applied over the right PPC, the homologue region in the left hemisphere or the right primary motor cortex. Stimulation was time-locked to the stimulus presentation with a stimulus onset asynchrony (SOA) varying between 50 and 200 ms. Our results indicate that TMS interfered mainly with the visuo-spatial task when applied over the right PPC at an early stage (50 ms post-stimulus). The interference effect of single-pulse TMS in the present visuo-spatial processing is revealed by a processing cost for ipsilateral targets. These results are in agreement with neuropsychological and brain imaging studies showing a right hemispheric dominance in visuo-spatial processing but add crucial information about the time-course of visuo-spatial processing within the right PPC.     

Transcranial magnetic stimulation to the parietal lobes reduces detection of contralateral somatosensory stimuli

OBJECTIVES: Neglect has been described in patients with lesions of the parietal cortex and has been interpreted as a disorder of the allocation of spatial attention. The persistence of neglect has been linked to poor rehabilitation outcome in patients suffering from acute stroke. Transcranial magnetic stimulation (TMS) applied to the parietal cortex has been shown to induce changes in the perception of stimuli including tactile stimulation of the fingers contra- and ipsilateral to the stimulated hemisphere. MATERIAL AND METHODS: In the current study, eleven normal young subjects performed a detection task for cutaneous electrical stimuli to the left or right forearm that had been precued by a preceding visual warning stimulus. To investigate the role of the parietal cortical areas for attentional processes TMS was applied to frontal and parietal scalp sites of each hemisphere in the cue-target interval before the somatosensory stimulus. RESULTS: Right and left parietal stimulation led to reduced detection sensitivity for near threshold stimuli to the forearm contralateral to the stimulated hemisphere without hemispheric differences. Ipsilateral tactile perception was not influenced by parietal TMS and there was no change in perception after frontal stimulation to left or right scalp sites. CONCLUSION: This pattern of results is consistent with a role of the right and left parietal lobe in the distribution of spatial attention and provides an experimental basis for possible therapeutical application of TMS to improve attentional deficits in stroke patients.     

Effects of transcranial magnetic stimulation of the posterior parietal cortex on saccades and vergence.

Previous studies showed that transcranial magnetic stimulation (TMS) of the posterior parietal cortex (PPC) prolongs the latency of intentional saccades. We examined whether a similar effect exists for reflexive saccades and vergence. To elicit reflexive movements, a gap paradigm was used; lateral saccades and vergence along the median plane were interleaved. TMS was applied on the right PPC 80 ms after target onset. Blocks without TMS were performed and a control experiment with TMS over the primary motor cortex. The latter had no effect on the latency of any type of movements. In contrast, stimulation of the PPC increased the latency of both saccades and vergence, suggesting that the PPC is involved in the triggering of reflexive movements both in direction and in depth.     

Maintenance of visual stability in the human posterior parietal cortex

Visual stability refers to our stable visuospatial perceptions despite the unstable visual input caused by saccades. Functional neuroimaging results, studies on patients with posterior parietal cortex (PPC) lesions, and single-unit recordings in the lateral intraparietal sulcus of primates indirectly suggest that the PPC might be a potential locus of visual stability through its involvement with spatial remapping. Here we directly explored the role of the PPC in visual stability by applying transcranial magnetic stimulation (TMS) while participants performed a perisaccadic displacement detection task. We show that TMS over the PPC but not a frontal control site alters sensitivity to displacement detection when administered just before contralateral saccades and that a general impairment in attention or in the perception of apparent motion cannot account for the decreased sensitivity. The specific relationship between the timing of TMS and saccade direction demonstrates that saccadic suppression of displacement (SSD) is likely a consequence of noisy contralateral spatial representations in the PPC around the time of a saccade. The same mechanism may keep the unstable visual world in the temporal proximity of saccades from reaching our consciousness.     

Effects of rTMS conditioning over the fronto-parietal network on motor versus visual attention

Many studies have shown that visuospatial orienting attention depends on a network of frontal and parietal areas in the right hemisphere. Rushworth et al. [Rushworth, M. F., Krams, M., & Passingham, R. E. The attentional role of the left parietal cortex: The distinct lateralization and localization of motor attention in the human brain. Journal of Cognitive Neuroscience, 13, 698-710, 2001] have recently provided evidence for a left-lateralized network of parietal areas involved in motor attention. Using two variants of a cued reaction time (RT) task, we set out to investigate whether high-frequency repetitive transcranial magnetic stimulation (rTMS; 5 Hz) delivered "off-line" in a virtual lesion paradigm over the right or left dorsolateral prefrontal cortex (DLPFC) or the posterior parietal cortex (PPC) would affect performance in a motor versus a visual attention task. Although rTMS over the DLPFC on either side did not affect RT performance on a spatial orienting task, it did lead to an increase in the RTs of invalidly cued trials in a motor attention task when delivered to the left DLPFC. The opposite effect was found when rTMS was delivered to the PPC: In this case, conditioning the right PPC led to increased RTs in invalidly cued trials located in the left hemispace, in the spatial orienting task. rTMS over the PPC on either side did not affect performance in the motor attention task. This double dissociation was evident in the first 10 min after rTMS conditioning. These results enhance our understanding of the networks associated with attention. They provide evidence of a role for the left DLPFC in the mechanisms of motor preparation, and confirm Mesulam's original proposal for a right PPC dominance in spatial attention [Mesulam, M. M. A cortical network for directed attention and unilateral neglect. Annals of Neurology, 10, 309-325, 1981].     

Novel ‘hunting’ method using transcranial magnetic stimulation over parietal cortex disrupts visuospatial sensitivity in relation to motor thresholds

There is considerable inter-study and inter-individual variation in the scalp location of parietal sites where transcranial magnetic stimulation (TMS) may modulate visuospatial behaviours (e.g. see Ryan, Bonilha, & Jackson, 2006); and no clear consensus on methods for identifying such sites. Here we introduce a novel TMS “hunting paradigm” that allows rapid, reliable identification of a site over the right anterior intraparietal sulcus (IPS), where short trains (at 10 Hz for 0.5 s) of TMS disrupt performance of a visuospatial task. The task involves detection of a small peripheral gap (at 14° eccentricity), on one or other (known) side of an extended (29°) horizontal line centred on fixation. Signal-detection analysis confirmed that TMS at the right IPS site reduced sensitivity (d′) for gap targets in the left visual hemifield. A further experiment showed that the same right-parietal TMS increased sensitivity instead for gaps in the right hemifield. Comparing TMS across a grid of scalp locations around the identified ‘hotspot’ confirmed the spatial-specificity of the effective site. Assessment of the TMS intensity required to produce the phenomena found this was linearly related to individuals’ resting motor TMS threshold over hand M1. Our approach provides a systematic new way to identify an effective site and intensity in individuals, at which TMS over right-parietal cortex reliably changes visuospatial sensitivity.     

The timing of the involvement of the frontal eye fields and posterior parietal cortex in visual search

The frontal eye fields (FEFs) and posterior parietal cortex (PPC) are important for target detection in conjunction visual search but the relative timings of their contribution have not been compared directly. We addressed this using temporally specific double pulse transcranial magnetic stimulation delivered at different times over FEFs and PPC during performance of a visual search task. Disruption of performance was earlier (0/40 ms) with FEF stimulation than with PPC stimulation (120/160 ms), revealing a clear and substantial temporal dissociation of the involvement of these two areas in conjunction visual search. We discuss these timings with reference to the respective roles of FEF and PPC in the modulation of extrastriate visual areas and selection of responses.     

Using state-dependency of transcranial magnetic stimulation (TMS) to investigate letter selectivity in the left posterior parietal cortex: a comparison of TMS-priming and TMS-adaptation paradigms

The state-dependency of transcranial magnetic stimulation (TMS) can be used to investigate the neural properties of subregions of the stimulated region. The objective of the present study was to determine whether state-dependency can reveal letter selectivity in the left posterior parietal cortex (PPC), a region known to contain letter-selective neurons. In two experiments, we used visual priming and adaptation to modulate the initial activation state of the left PPC prior to application of TMS. In the priming experiment, TMS was applied over the left PPC during the delay between the prime and the target stimulus on each experimental trial. Left PPC TMS reversed the effects of priming by facilitating the detection of non-primed letters, whereas detection of primed letters was unaffected. As neurons tuned to non-primed letters were less active at the time of TMS application than neurons tuned to the primed letters, this finding demonstrates that TMS preferentially facilitates the detection of attributes encoded by the less active neural populations. A similar facilitation of the less active neural populations was observed when adaptation was used to suppress letter-selective neurons prior to application of TMS. Our study demonstrates that TMS-priming and TMS-adaptation paradigms can reveal letter selectivity in the left PPC and thus be useful in the study of language processes. Our results also show that the state-dependent TMS effects obtained with visual priming are similar to those found with TMS adaptation: in both cases, attributes encoded by the less active neural populations are preferentially facilitated.     

Reflexive and preparatory selection and suppression of salient information in the right and left posterior parietal cortex

Attentional cues can trigger activity in the parietal cortex in anticipation of visual displays, and this activity may, in turn, induce changes in other areas of the visual cortex, hence, implementing attentional selection. In a recent TMS study [Mevorach, C., Humphreys, G. W., & Shalev, L. Opposite biases in salience-based selection for the left and right posterior parietal cortex. Nature Neuroscience, 9, 740-742, 2006b], it was shown that the posterior parietal cortex (PPC) can utilize the relative saliency (a nonspatial property) of a target and a distractor to bias visual selection. Furthermore, selection was lateralized so that the right PPC is engaged when salient information must be selected and the left PPC when the salient information must be ignored. However, it is not clear how the PPC implements these complementary forms of selection. Here we used on-line triple-pulse TMS over the right or left PPC prior to or after the onset of global/local displays. When delivered after the onset of the display, TMS to the right PPC disrupted the selection of the more salient aspect of the hierarchical letter. In contrast, left PPC TMS delivered prior to the onset of the stimulus disrupted responses to the lower saliency stimulus. These findings suggest that selection and suppression of saliency, rather than being "two sides of the same coin," are fundamentally different processes. Selection of saliency seems to operate reflexively, whereas suppression of saliency relies on a preparatory phase that "sets up" the system in order to effectively ignore saliency.     

Modulation of a fronto-parietal network in event-based prospective memory: an rTMS study

Event-based prospective memory (PM) is a multi-component process that requires remembering the delayed execution of an intended action in response to a pre-specified PM cue, while being actively engaged in an ongoing task. Some neuroimaging studies have suggested that both prefrontal and parietal areas are involved in the maintenance and realization of delayed intentions. In the present study, transcranial magnetic stimulation (TMS) was used to investigate the causal involvement of frontal and parietal areas in different stages of the PM process (in particular, target checking and intention retrieval), and to determine the specific contribution of these regions to PM performance.Our results demonstrate that repetitive TMS (rTMS) interferes with prospective memory performance when applied at 150-350 ms to the right dorsolateral prefrontal cortex (DLPFC), and at 400-600 ms when applied to the left posterior parietal cortex (PPC).The present study provides clear evidence that the right DLPFC plays a crucial role in early components of the PM process (target checking), while the left PPC seems to be mainly involved in later processes, such as the retrieval of the intended action.     

Concurrent TMS-fMRI reveals dynamic interhemispheric influences of the right parietal cortex during exogenously cued visuospatial attention

We used concurrent transcranial magnetic stimulation and functional MRI (TMS-fMRI) during a visuospatial cueing paradigm in humans, to study the causal role of the right angular gyrus (AG) as a source of attentional control. Our findings show that TMS over the right AG (high vs. low intensity) modulates neural responses interhemispherically, in a manner that varies dynamically with the current attentional condition. The behavioural impact of such TMS depended not only on the target hemifield but also on exogenous cue validity, facilitating spatial reorienting to invalidly cued right visual targets. On a neural level, right AG TMS had corresponding interhemispheric effects in the left AG and left retinotopic cortex, including area V1. We conclude that the direction of covert visuospatial attention can involve dynamic interplay between the right AG and remote interconnected regions of the opposite left hemisphere, whereas our findings also suggest that the right AG can influence responses in the retinotopic visual cortex.