Hemispheric asymmetry in visuospatial attention assessed with transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) was used to study visuospatial attention processing in ten healthy volunteers. In a forced choice recognition task the subjects were confronted with two symbols simultaneously presented during 120 ms at random positions, one in the left and the other in the right visual field. The subject had to identify the presented pattern out of four possible combinations and to press the corresponding response key within 2 s. Double-pulse TMS (dTMS) with a 100-ms interstimulus interval (ISI) and an intensity of 80% of the stimulator output (corresponding to 110-120% of the motor threshold) was applied by a non-focal coil over the right or left posterior parietal cortex (PPC, corresponding to P3/P4 of the international 10-20 system) at different time intervals after onset of the visual stimulus (starting at 120 ms, 270 ms and 520 ms). Double-pulse TMS over the right PPC starting at 270 ms led to a significant increase in percentage of errors in the contralateral, left visual field (median: 23% with TMS vs 13% without TMS, P=0.0025). TMS applied earlier or later showed no effect. Furthermore, no significant increase in contra- or ipsilateral percentage of errors was found when the left parietal cortex was stimulated with the same timing. These data indicate that: (1) parietal influence on visuospatial attention is mainly controlled by the right lobe since the same stimulation over the left parietal cortex had no significant effect, and (2) there is a vulnerable time window to disturb this cortical process, since dTMS had a significant effect on the percentage of errors in the contralateral visual hemifield only when applied 270 ms after visual stimulus presentation.     

Hemispheric asymmetry in memory-guided pointing during single-pulse transcranial magnetic stimulation of human parietal cortex

Dorsal posterior parietal cortex (PPC) has been implicated through single-unit recordings, neuroimaging data, and studies of brain-damaged humans in the spatial guidance of reaching and pointing movements. The present study examines the causal effect of single-pulse transcranial magnetic stimulation (TMS) over the left and right dorsal posterior parietal cortex during a memory-guided "reach-to-touch" movement task in six human subjects. Stimulation of the left parietal hemisphere significantly increased endpoint variability, independent of visual field, with no horizontal bias. In contrast, right parietal stimulation did not increase variability, but instead produced a significantly systematic leftward directional shift in pointing (contralateral to stimulation site) in both visual fields. Furthermore, the same lateralized pattern persisted with left-hand movement, suggesting that these aspects of parietal control of pointing movements are spatially fixed. To test whether the right parietal TMS shift occurs in visual or motor coordinates, we trained subjects to point correctly to optically reversed peripheral targets, viewed through a left-right Dove reversing prism. After prism adaptation, the horizontal pointing direction for a given visual target reversed, but the direction of shift during right parietal TMS did not reverse. Taken together, these data suggest that induction of a focal current reveals a hemispheric asymmetry in the early stages of the putative spatial processing in PPC. These results also suggest that a brief TMS pulse modifies the output of the right PPC in motor coordinates downstream from the adapted visuomotor reversal, rather than modifying the upstream visual coordinates of the memory representation.     

Self-specific processing in the default network: a single-pulse TMS study

In examining neural processing specific to the self, primarily by contrasting self-related stimuli with non-self-related stimuli (i.e., self vs. other), neuroimaging studies have activated a consistent set of regions, including medial prefrontal cortex (MPFC), precuneus, and right and left inferior parietal cortex. However, criticism has arisen that this network may not be specific to self-related processing, but instead reflects a more general aspect of cortical processing. For example, it is almost identical to the active network of the resting state, the "default" mode, when the subject is free to think about anything at all. We tested the self-specificity of this network by using transcranial magnetic stimulation (TMS) to briefly disrupt local cortical processing while subjects rated adjectives as like or unlike themselves or their best friend. Healthy volunteers show a self-reference effect (SRE) in this task, in which performance with self-related items is superior to that with other-related items. As individual adjectives appeared on a monitor, single-pulse TMS was applied at five different times relative to stimulus onset (SOA: stimulus onset asynchrony) ranging from 0 to 480 ms. In 18 subjects, TMS to left parietal cortex suppressed the SRE from 160 to 480 ms. SRE suppression occurred at later SOA with TMS to the right parietal cortex. In contrast, no effects were seen with TMS to MPFC. Together with our previous work, these results provide evidence for a self-specific processing system in which midline and lateral inferior parietal cortices, as elements of the default network, play a role in ongoing self-awareness.     

Modulation of excitatory and inhibitory circuits for visual awareness in the human right parietal cortex

The balance of specific patterns of excitation and inhibition in critical regions of both hemispheres could be relevant in orienting attention over the extrapersonal space. In the present study a group of normal subjects had to detect small rectangular stimuli presented briefly on a computer screen in three different conditions: unilateral presentation either to left or right visual periphery or bilateral simultaneous presentation. Paired transcranial magnetic stimulation (TMS), was applied over the right parietal cortex 150 ms after the presentation of the visual stimuli with different inter-stimulus intervals (ISIs: 1, 3,5 and 10 ms). When paired TMS was applied 150 ms, but not 100 ms, after simultaneous visual presentation, the number of failures in detecting left targets increased compared to the single-pulse condition if the ISI was 3 ms; on the contrary, it decreased if the ISI was 5 ms. No effects were seen when paired pulses of the same intensity were delivered. These findings provide evidence of a supramodal-specific pattern of excitability of the right posterior parietal cortex in processing visuospatial information.     

Time series analysis of postural responses to combined visual pitch and support surface tilt

Transcranial magnetic stimulation (TMS) is a neurophysiological tool that can transiently influence brain excitability and improve cognitive performance. Facilitation effects induced by low frequency repetitive TMS on memory functions have been shown in a few studies in young and healthy participants [29] and in older individuals with memory complaints [40]. However, regions specifically involved in encoding and retrieval were not always systematically targeted. We thus aimed to facilitate episodic memory with online TMS systematically applied over the left or right dorsolateral prefrontal cortex (DLPFC) while participants were performing a recognition task. We applied online paired-pulse TMS (ppTMS) (15 ms inter-stimulus interval) either during encoding or retrieving of verbal or non-verbal material. Participants were 11 right-handed young individuals (21.33 ± 2.27 years old). Repeated measures ANOVA showed shorter reaction time when ppTMS are applied over the left DLPFC during encoding as compared to right homologous stimulation or to Sham condition. In contrast, ppTMS over the right DLPFC during retrieval was associated with shorter reaction times compared to left homologous stimulation. Overall, our data support for the first time that online ppTMS over the DLPFCs is capable of hastening memory processes in young and healthy individuals.     

Spatial working memory performance after high-frequency repetitive transcranial magnetic stimulation of the left and right posterior parietal cortex in humans

The effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) at the left or right posterior parietal cortex were studied using a spatial working memory task. Eight subjects were stimulated over the P3 and P4 electrode site at 115% of the motor threshold (frequency 25 Hz, trains of 200 ms) during the 1000-ms delay of the spatial working memory task, or received sham stimulation. It was found that the reaction times were slower during right-parietal rTMS than during left-parietal rTMS. No differences were found between the percentages correct responses. These results are in line with recent neuroimaging findings and data from patients with cerebral lesions, suggesting that the posterior parietal cortex is especially involved in spatial processing, and provide converging evidence for recent theories on hemispheric specialization.     

Cortico-cortical interactions in spatial attention: A combined ERP/TMS study

To gain insight into the neural basis of visual attention, we combined transcranial magnetic stimulation (TMS) and event-related potentials (ERPs) during a visual search task. Single-pulse TMS over right posterior parietal cortex (rPPC) delayed response times to targets during conjunction search, and this behavioral effect had a direct ERP correlate. The early phase of the N2pc component that reflects the focusing of attention onto target locations in a search display was eliminated over the right hemisphere when TMS was applied there but was present when TMS was delivered to a control site (vertex). This finding demonstrates that rPPC TMS interferes with attentional selectivity in remote visual areas.     

Contributions of human parietal and frontal cortices to attentional control during conflict resolution: a 1-Hz offline rTMS study

Various brain regions contribute to aspects of attentional control in conflict resolution. Here, we used transcranial magnetic stimulation (TMS) to examine the functions of posterior parietal cortex (PPC) and dorsal medial frontal cortex (dMFC) in a visual flanker task. Participants responded to a central target that was flanked by congruent, neutral or incongruent stimuli on the left or right. Offline low-frequency repetitive TMS (1 Hz, 110% motor threshold, 20 min) was applied to right PPC or dMFC. Performance, as measured by reaction times and accuracy, was established at baseline, after rTMS, and sham stimulation before or after active rTMS. After rTMS to right PPC, the interference of flankers presented in the left visual hemispace diminished selectively. By contrast, after rTMS over the right dMFC, flanker effects in both visual fields remained. Our results suggest that right PPC specifically contributes to the assignment of spatial attention during stimulus encoding.     

Role of the posterior parietal cortex in updating reaching movements to a visual target.

The exact role of posterior parietal cortex (PPC) in visually directed reaching is unknown. We propose that, by building an internal representation of instantaneous hand location, PPC computes a dynamic motor error used by motor centers to correct the ongoing trajectory. With unseen right hands, five subjects pointed to visual targets that either remained stationary or moved during saccadic eye movements. Transcranial magnetic stimulation (TMS) was applied over the left PPC during target presentation. Stimulation disrupted path corrections that normally occur in response to target jumps, but had no effect on those directed at stationary targets. Furthermore, left-hand movement corrections were not blocked, ruling out visual or oculomotor effects of stimulation.     

Transcranial magnetic stimulation of the posterior parietal cortex delays the latency of both isolated and combined vergence-saccade movements in humans

To explore the 3D visual environment most frequently we make combined saccade-vergence eye movements. We studied the effect of transcranial magnetic stimulation (TMS) of the right posterior parietal cortex (rPPC) on such combined eye movements versus isolated saccade and vergence. In the main experiment, TMS was applied on the rPPC 80, 90 or 100 ms after target onset. In a control experiment, TMS was applied over the primary motor cortex at 90 ms after the target presentation. TMS trials were compared with no-TMS trials. TMS of the motor cortex had no effect at all on eye movements. TMS of the rPPC had no effect on the accuracy of eye movements, but it caused a latency increase: the increase was similar for the two components of the combined saccade-vergence movements, and it did not alter the naturally existing tight relationship of latency between the two components. Furthermore, the amount of latency prolongation was similar to that of isolated vergence, and of saccades in either direction (ipsilateral or contralateral relative to the stimulated site). Latency prolongation was time-specific but in a different way for different types of eye movements: for combined and convergence eye movements, the critical time window was -130 ms or more prior to the onset of eye movement, while for saccades and divergence TMS was disruptive later, -110 ms or more prior to the onset of eye movements. The latency increase is attributed to the interference by the TMS with the fixation disengagement process, for which the rPPC is believed to be instrumental. These results suggest that fixation disengagement occurs earlier for convergence and combined eye movements than for saccades and divergence.     

Involvement of ipsilateral parieto-occipital cortex in the planning of reaching movements: Evidence by TMS

Involvement of the ipsilateral hemisphere during planning of reaching movements is still matter of debate. While it has been demonstrated that the contralateral hemisphere is dominant in visuo-motor integration, involvement of the ipsilateral hemisphere has also been proposed. Furthermore, a dominant role for left posterior parietal cortex has been shown in this process, independently of the hand and visual field involved. In this study, the possible involvement of ipsilateral parieto-occipital cortex in planning of reaching movements was investigated by transcranial magnetic stimulation (TMS). TMS was applied on four points of the parietal and occipital cortex at 50% (Time 1), 75% (Time 2) and 90% (Time 3) of reaction time from a go-signal to hand movement. The only effect observed was an increase in reaction time when a region around the parieto-occipital junction was stimulated at Time 2. These results provide further support to the hypothesis that, in the posterior parietal cortex, planning of reaching movements also relies on the ipsilateral hemisphere, in addition to the contralateral or dominant one.     

Executive control over response priming and conflict: a transcranial magnetic stimulation study

In the present study repetitive transcranial magnetic stimulation (rTMS) was utilised to interrupt neural activity in selected cortical areas at several different time periods while participants performed a stimulus-response correspondence (SRC) task. Responses are usually faster and less error-prone when stimulus (S) and response (R) features correspond than when they do not. Dual-route models of response preparation account for such SRC effects by postulating an indirect route performing S-R selection and a parallel direct route where S features prime their corresponding responses. SRC effects have recently been shown to depend on the preceding trial type, that is, SRC effects are largely reduced when preceded by a non-corresponding trial as compared to a preceding corresponding trial. Present results show that this context dependency of the SRC effect was hindered when rTMS was applied to the left dorsolateral prefrontal cortex (DLPFC) 500-300 ms before the onset of the next trial. Moreover, the SRC effect was reduced overall when applying rTMS volleys to the right posterior parietal cortex (PPC) for 200 ms with the onset of the visual stimulus. We conclude that the left DLPFC is involved in the context-dependent control of response conflicts, whereas the right PPC serves early visuomotor transformations and is, therefore, related to direct route priming.     

Neural activation during frequency-memory performance.

Lesion studies have demonstrated that frequency memory, or memory for the frequency of occurrence, is associated with prefrontal and not temporal lobe lesions. This study examined neural activation during performance on a frequency-memory-judgment task and a recognition-memory task, both using words. Relative to a control task, the authors observed peaks of activation during frequency-memory performance in the left ventrolateral prefrontal cortex (BA 45) and other areas typically associated with working memory (dorsolateral prefrontal cortex, posterior parietal cortex). Recognition performance was associated with activation in the same left ventrolateral prefrontal location as was observed with frequency memory. When comparing activation during frequency memory with activation during recognition memory, the authors found a suppression of activation in the hippocampus bilaterally during frequency memory. This study supports a neuroanatomical distinction between frequency and recognition memory.     

Decreased cortical response to verbal working memory following sleep deprivation

STUDY OBJECTIVE: To investigate the cerebral hemodynamic response to verbal working memory following sleep deprivation. DESIGN: Subjects were scheduled for 3 functional magnetic resonance imaging scanning visits: an initial screening day (screening state), after a normal night of sleep (rested state), and after 30 hours of sleep deprivation (sleep-deprivation state). Subjects performed the Sternberg working memory task alternated with a control task during an approximate 13-minute functional magnetic resonance imaging scan. SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: Results from 33 men (mean age, 28.6 +/- 6.6 years) were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Subjects performed the same Sternberg working memory task at the 3 states within the magnetic resonance imaging scanner. Neuroimaging data revealed that, in the screening and rested states, the brain regions activated by the Sternberg working memory task were found in the left dorsolateral prefrontal cortex, Broca's area, supplementary motor area, right ventrolateral prefrontal cortex, and the bilateral posterior parietal cortexes. After 30 hours of sleep deprivation, the activations in these brain regions significantly decreased, especially in the bilateral posterior parietal cortices. Task performance also decreased. A repeated-measures analysis of variance revealed that subjects at the screening and rested states had similar activation patterns, with each having significantly more activation than during the sleep-deprivation state. CONCLUSIONS: These results suggest that human sleep-deprivation deficits are not caused solely or even predominantly by prefrontal cortex dysfunction and that the paretal cortex, in particular, and other brain regions involved in verbal working memory exhibit significant sleep-deprivation vulnerability.     

Effect of transcranial magnetic stimulation on bimanual movements

Transcranial magnetic stimulation (TMS) of the motor cortex can interrupt voluntary contralateral rhythmic limb movements. Using the method of "resetting index" (RI), our study investigated the TMS effect on different types of bimanual movements. Six normal subjects participated. For unimanual movement, each subject tapped either the right or left index finger at a comfortable rate. For bimanual movement, index fingers of both hands tapped in the same (in-phase) direction or in the opposite (antiphase) direction. TMS was applied to each hemisphere separately at various intensities from 0.5 to 1.5 times motor threshold (MT). TMS interruption of rhythm was quantified by RI. For the unimanual movements, TMS disrupted both contralateral and ipsilateral rhythmic hand movements, although the effect was much less in the ipsilateral hand. For the bimanual in-phase task, TMS could simultaneously reset the rhythmic movements of both hands, but the effect on the contralateral hand was less and the effect on the ipsilateral hand was more compared with the unimanual tasks. Similar effects were seen from right and left hemisphere stimulation. TMS had little effect on the bimanual antiphase task. The equal effect of right and left hemisphere stimulation indicates that neither motor cortex is dominant for simple bimanual in-phase movement. The smaller influence of contralateral stimulation and the greater effect of ipsilateral stimulation during bimanual in-phase movement compared with unimanual movement suggest hemispheric coupling. The antiphase movements were resistant to TMS disruption, and this suggests that control of rhythm differs in the 2 tasks. TMS produced a transient asynchrony of movements on the 2 sides, indicating that both motor cortices might be downstream of the clocking command or that the clocking is a consequence of the 2 hemispheres communicating equally with each other.     

Transcranial magnetic stimulation over human dorsal-lateral posterior parietal cortex disrupts integration of hand position signals into the reach plan

Posterior parietal cortex (PPC) has been implicated in the integration of visual and proprioceptive information for the planning of action. We previously reported that single-pulse transcranial magnetic stimulation (TMS) over dorsal–lateral PPC perturbs the early stages of spatial processing for memory-guided reaching. However, our data did not distinguish whether TMS disrupted the reach goal or the internal estimate of initial hand position needed to calculate the reach vector. To test between these hypotheses, we investigated reaching in six healthy humans during left and right parietal TMS while varying visual feedback of the movement. We reasoned that if TMS were disrupting the internal representation of hand position, visual feedback from the hand might still recalibrate this signal. We tested four viewing conditions: 1) final vision of hand position; 2) full vision of hand position; 3) initial and final vision of hand position; and 4) middle and final vision of hand position. During the final vision condition, left parietal stimulation significantly increased endpoint variability, whereas right parietal stimulation produced a significant leftward shift in both visual fields. However, these errors significantly decreased with visual feedback of the hand during both planning and control stages of the reach movement. These new findings demonstrate that 1) visual feedback of hand position during the planning and early execution of the reach can recalibrate the perturbed signal and, importantly, and 2) TMS over dorsal–lateral PPC does not disrupt the internal representation of the visual goal, but rather the reach vector, or more likely the sense of initial hand position that is used to calculate this vector.     

The effect of transcranial magnetic stimulation on the latencies of vertical saccades

In this study, we investigated the effect of transcranial magnetic stimulation (TMS) over the right posterior parietal cortex (PPC) on the latency of two different types of visually-guided vertical saccades: reflexive saccades triggered by the sudden onset of a target, and saccades towards target locations known in advance. For this reason, we used two oculomotor tasks: a gap and a delay task, respectively. Nine normal subjects performed vertical saccades at ±7.5 and ±15°. TMS was applied at 80 and 100 ms after target onset in the gap task, and after fixation offset in the delay task. Without TMS, we confirmed a latency asymmetry in the gap task favouring upward saccades at the lower eccentricity (7.5°), and a latency symmetry in the delay task. TMS increased the latencies of all saccades in the delay task, when delivered at 100 ms. This effect was mostly pronounced for downward saccades at 7.5°. As a result, saccade latencies showed an asymmetry in this condition, similar to the one observed in the gap task without TMS. The gap task with TMS resulted in a variable latency distribution and no significant overall effect on saccade latency. Our results indicate that the right PPC is involved in the initiation of vertical saccades in the delay task, and that this involvement appears to be enhanced for downward saccades. A conclusion for the involvement of this area in the gap task could not be drawn from this study.     

Effects of motor cortical stimulation on the excitability of contralateral motor and sensory cortices

Single pulses of transcranial magnetic stimulation (TMS) were applied to the right hemisphere over either the hand sensory area, the hand motor area (M1), ventral premotor area (vPM), dorsolateral prefrontal cortex, or 10 cm away from head (sham stimulation) in order to test the effect on motor evoked potentials (MEPs) elicited by single pulse TMS or transcranial electrical stimulus (TES) over the left M1 or the somatosensory evoked potential (SEP) elicited by an electrical stimulus to the right median nerve. The interstimulus intervals (ISIs) for MEP experiments were 50, 100, 150, 200, 300 and 400 ms, with those for SEP experiments being adjusted for the impulse conduction time from the wrist to the cortex. TMS over the right M1 reduced MEPs elicited by TMS of the left motor cortex at ISIs of 50–150 ms, whereas MEPs produced by TES were unaffected. TMS over M1 and vPM facilitated the contralateral cortical median nerve SEPs at an ISI of 100–200 ms, whereas it had no effect on tibial nerve SEPs or paired median nerve stimulation SEP. Based on these results, we conclude that at around 150-ms intervals, TMS over the motor areas (M1 and vPM) reduces the excitability of the contralateral motor area. This has a secondary effect of enhancing the responsiveness of the sensory cortex through cortico-cortical connections.     

Hemiextinction induced by transcranial magnetic stimulation over the right temporo-parietal junction

Whereas it is widely accepted that the parietal cortex is crucial for visual attention, the role of the temporal cortex and the temporo-parietal junction (TPJ) is less clear. There are clinical reports of patients with lesions in different posterior temporal areas which exhibit contralateral visual neglect but this syndrome seems to be less frequent than in patients with parietal lesions. In a previous study, we could show that single-pulse transcranial magnetic stimulation (TMS) over the right inferior parietal cortex is capable to induce both neglect-like and extinction-like impairments of performance in normal subjects. In the present study, we used this method to examine the functional role of the superior temporal gyrus (STG) and the TPJ of the right hemisphere for visuo-spatial attention. Healthy volunteers were asked to detect small dots appearing for 40 ms unilaterally on right or left side or bilaterally on a computer screen. TMS was applied over the TPJ or STG. TMS over the TPJ induced an extinction-like behavioral pattern to the contralateral hemifield. TMS over the STG had no effect. The results demonstrate a functional involvement of the TPJ in visuo-attentional processing of competing stimuli in both hemifields. This region is part of the cortical network mediating stimulus-driven attention which is relevant for processing of competing stimuli.     

TMS activation of interhemispheric pathways between the posterior parietal cortex and the contralateral motor cortex

Using a twin coil transcranial magnetic stimulation (tc-TMS) approach we have previously demonstrated that facilitation may be detected in the primary motor cortex (M1) following stimulation over the ipsilateral caudal intraparietal sulcus (cIPS). Here we tested the interhemispheric interactions between the IPS and the contralateral motor cortex (M1). We found that conditioning the right cIPS facilitated contralateral M1 when the conditioning stimulus had an intensity of 90% resting motor threshold (RMT) but not at 70% or 110% RMT. Facilitation was maximal when the interstimulus interval (ISI) between cIPS and M1 was 6 or 12 ms. These facilitatory effects were mediated by interactions with specific groups of interneurons in the contralateral M1. In fact, short intracortical inhibition (SICI) was reduced following cIPS stimulation. Moreover, additional comparison of facilitation of responses evoked by anterior–posterior versus posterior–anterior stimulation of M1 suggested that facilitation was more effective on early I1/I2 circuits than on I3 circuits. In contrast to these effects, stimulation of anterior IPS (aIPS) at 90% RMT induced inhibition, instead of facilitation, of contralateral M1 at ISIs of 10–12 ms. Finally, we found similar facilitation between left cIPS and right M1 although the conditioning stimuli had to have a higher intensity compared with stimulation of right cIPS (110% instead of 90% RMT). These findings demonstrate that different subregions of the posterior parietal cortex (PPC) in humans exert both facilitatory and inhibitory effects towards the contralateral primary motor cortex. These corticocortical projections could contribute to a variety of motor tasks such as bilateral manual coordination, movement planning in space and grasping.