Neuronal responses in area 7a to multiple-stimulus displays: I. neurons encode the location of the salient stimulus.

The primate posterior parietal cortex (PPC) plays an important role in representing and recalling spatial relationships and in the ability to orient visual attention. This is evidenced by the parietal activation observed in brain imaging experiments performed during visuo- spatial tasks, and by the contralateral neglect syndrome that often accompanies parietal lesions. Individual neurons in monkey parietal cortex respond vigorously to the appearance of single, behaviorally relevant stimuli, but little is known about how they respond to more complex visual displays. The current experiments addressed this issue by recording activity from single neurons in area 7a of the PPC in monkeys performing a spatial version of a match-to-sample task. The task required them to locate salient stimuli in multiple-stimulus displays and release a lever after a subsequent stimulus appeared at the same location. Neurons responded preferentially to the appearance of salient stimuli inside their receptive fields. The presence of multiple stimuli did not affect appreciably the spatial tuning of responses in the majority of neurons or the population code for the location of the salient stimulus. Responses to salient stimuli could be distinguished from background stimuli approximately 100 ms after the onset of the cue. These results suggest that area 7a neurons represent the location of the stimulus attracting the animal's attention and can provide the spatial information required for directing attention to a salient stimulus in a complex scene.     

Dorsal posterior parietal rTMS affects voluntary orienting of visuospatial attention

Patients with lesions in posterior parietal cortex (PPC) are relatively unimpaired in voluntarily directing visual attention to different spatial locations, while many neuroimaging studies in healthy subjects suggest dorsal PPC involvement in this function. We used an offline repetitive transcranial magnetic stimulation (rTMS) protocol to study this issue further. Ten healthy participants performed a cue-target paradigm. Cues prompted covert orienting of spatial attention under voluntary control to either a left or right visual field position. Targets were flashed subsequently at the cued or uncued location, or bilaterally. Following rTMS over right dorsal PPC, (i) the benefit for target detection at cued versus uncued positions was preserved irrespective of cueing direction (left- or rightward), but (ii) leftward cueing was associated with a global impairment in target detection, at all target locations. This reveals that leftward orienting was still possible after right dorsal PPC stimulation, albeit at an increased overall cost for target detection. In addition, rTMS (iii) impaired left, but (iv) enhanced right target detection after rightward cueing. The finding of a global drop in target detection during leftward orienting with a spared, relative detection benefit at the cued (left) location (i-ii) suggests that right dorsal PPC plays a subsidiary rather than pivotal role in voluntary spatial orienting. This finding reconciles seemingly conflicting results from patients and neuroimaging studies. The finding of attentional inhibition and enhancement occurring contra- and ipsilaterally to the stimulation site (iii-iv) supports the view that spatial attention bias can be selectively modulated through rTMS, which has proven useful to transiently reduce visual hemispatial neglect.     

Independence of visual awareness from the scope of attention: an electrophysiological study

Recent brain imaging studies have revealed that increased neuralactivity along the ventral visual stream and parietal and frontalareas is associated with visual awareness. In order to studythe time-course and temporal aspects of awareness, we examinedelectrophysiological correlates of conscious vision in two maskingexperiments. The differences in event-related potentials (ERPs)between unmasked (consciously recognized) and masked (unrecognized)stimuli were considered to be electrophysiological correlatesof awareness. Two attentional conditions (global, local) wereincluded to examine the relationship between the scope of attentionand awareness. Two ERP-deflections were found to correlate withawareness. First, awareness was associated with a posteriornegative amplitude shift 130–320 ms after the stimulus.This effect was present in both attention conditions, suggestingthat it emerges independent of the scope of attention. Second,ERPs to unmasked stimuli became more positive as compared withmasked stimuli around 400 ms, peaking at parietal sites. Thiseffect was attenuated in the local attention condition, althoughthe participants were aware of the stimuli, suggesting thatthe late positivity does not directly correlate with visualawareness. The results imply that the earlier negativity isthe earliest and most direct correlate of visual awareness.     

Neuronal responses in area 7a to multiple stimulus displays: II. responses are suppressed at the cued location.

Everyday visual scenes contain a variety of stimuli that vary in their significance. The companion paper demonstrates that neurons in the posterior parietal cortex (PPC) are capable of encoding the spatial locations of the salient stimulus in multiple stimulus scenes. The present experiment sought to address how neuronal responses to stimuli appearing in the receptive field are modulated after attention has been drawn to one of multiple stimuli in a visual scene. We recorded from area 7a of the PPC in monkeys trained to do a spatial version of a match-to-sample task. The results show that neuronal responses are greatly suppressed when stimuli appear at previously attended locations. No reduction in responsiveness is observed for locations where stimuli had previously appeared but did not draw attention. These results support the hypothesis that area 7a has a role in redirecting attention to stimuli appearing at novel, unattended locations.     

Right parietal cortex plays a critical role in change blindness

There is increasing evidence from functional magnetic resonance imaging (fMRI) that visual awareness is not only associated with activity in ventral visual cortex but also with activity in the parietal cortex. However, due to the correlational nature of neuroimaging, it remains unclear whether this parietal activity plays a causal role in awareness. In the experiment presented here we disrupted activity in right or left parietal cortex by applying repetitive transcranial magnetic stimulation (rTMS) over these areas while subjects attempted to detect changes between two images separated by a brief interval (i.e. 1-shot change detection task). We found that rTMS applied over right parietal cortex but not left parietal cortex resulted in longer latencies to detect changes and a greater rate of change blindness compared with no TMS. These results suggest that the right parietal cortex plays a critical role in conscious change detection.     

The neural correlates of conscious vision

Conflicting accounts of the neurobiology of consciousness have emerged from previous imaging studies. Some studies suggest that visual consciousness relates to a distributed network of frontal and partietal regions while others point to localized activity within individual visual areas. While the two positions seem mutually exclusive, timing issues may help reconcile the two. Networks that appear unified in functional magnetic resonance imaging (fMRI) studies may reflect processes that are widely distributed in time. To help resolve this issue, we have investigated timing across a network correlating with consciousness in parallel fMRI and evoked potential (EP) studies of grating stimuli. At threshold, a stimulus is perceived on some occasions but not on others, dissociating sensory input and perception. We have found correlates of consciousness in the occipital lobe at 100 ms and in parietal, frontal, auditory and motor regions from 260 ms onwards. The broad temporal and spatial distribution of activity argues against a unified, distributed fronto-parietal correlate of consciousness. Instead, it suggests that correlates of consciousness are divided into primary and secondary network nodes, with early activity in the occipital lobe correlating with perception and later activity in downstream areas with secondary processes contingent on the outcome of earlier perceptual processing.     

Pre- and poststimulus alpha rhythms are related to conscious visual perception: a high-resolution EEG study

Conscious and unconscious visuospatial processes have been related to parietooccipital cortical activation as revealed by late visual-evoked potentials. Here the working hypothesis was that a specific pattern of pre- and poststimulus theta (about 4-6 Hz) and alpha (about 6-12 Hz) rhythms is differently represented during conscious compared with unconscious visuospatial processes. Electroencephalographic (EEG) data (128 channels) were recorded in normal adults during a visuospatial task. A cue stimulus appeared at the right or left (equal probability) monitor side for a "threshold time" inducing about 50% of correct recognitions. It was followed (2 s) by visual go stimuli at spatially congruent or incongruent position with reference to the cue location. Left (right) mouse button was clicked if the go stimulus appeared at the left (right) monitor side. Then, subjects said "seen" if they had detected the cue stimulus or "not seen" if missed (self-report). Sources of theta and alpha rhythms during seen and not seen EEG epochs were estimated by low-resolution electromagnetic brain topography software. Results showed that the prestimulus "low-band" (about 6-10 Hz) alpha rhythms in frontal, parietal, and occipital areas were stronger in power in the seen than in the not seen trials. After the visual stimulation, the power of the "high-band" (about 10-12 Hz) alpha rhythms in parietal and occipital areas decreased more in the seen than in the not seen trials. The present results suggest that visuospatial consciousness covary--presumably with a facilitatory effect--with the power of both pre- and poststimulus alpha rhythms.     

Hearing lips: gamma-band activity during audiovisual speech perception

Auditory pattern changes have been shown to elicit increases in magnetoencephalographic gamma-band activity (GBA) over left inferior frontal cortex, forming part of the putative auditory ventral "what" processing stream. The present study employed a McGurk-type paradigm to assess whether GBA would be associated with subjectively perceived changes even when auditory stimuli remain unchanged. Magnetoencephalograms were recorded in 16 human subjects during audiovisual mismatch perception. Both infrequent visual (auditory /ta/ + visual /pa/) and acoustic deviants (auditory/pa/ + visual /ta/) were compared with frequent audiovisual standards (auditory /ta/ and visual /ta/). Statistical probability mapping revealed spectral amplitude increases at approximately 75 and approximately 78 Hz to visual deviants. GBA to visual deviants peaked 160 ms after auditory stimulus onset over posterior parietal cortex, at 270 ms over occipital areas and at 320 ms over left inferior frontal cortex. The latter GBA enhancement was consistent with the increase observed previously to pure acoustic mismatch, supporting a role of left inferior frontal cortex for the representation of perceived auditory pattern change. The preceding gamma-band changes over posterior areas may reflect processing of incongruent lip movements in visual motion areas and back-projections to earlier visual cortex.     

Human parietal "reach region" primarily encodes intrinsic visual direction, not extrinsic movement direction, in a visual motor dissociation task

Posterior parietal cortex (PPC) participates in the planning of visuospatial behaviors, including reach movements, in gaze-centered coordinates. It is not known if these representations encode the visual goal in retinal coordinates, or the movement direction relative to gaze. Here, by dissociating the intrinsic retinal stimulus from the extrinsic direction of movement, we show that PPC employs a visual code. Using delayed pointing and event-related functional magnetic resonance imaging, we identified a cluster of PPC regions whose activity was topographically (contralaterally) related to the direction of the planned movement. We then switched the normal visual-motor spatial relationship by adapting subjects to optical left/right reversing prisms. With prisms, movement-related PPC topography reversed, remaining tied to the retinal image. Thus, remarkably, the PPC region in each hemisphere now responded more for planned ipsilateral pointing movements. Other non-PPC regions showed the opposite world- or motor-fixed pattern. These findings suggest that PPC primarily encodes not motor commands but movement goals in visual coordinates.     

The planning and guiding of reading saccades: a repetitive transcranial magnetic stimulation study.

A previous positron emission tomography study that investigated the cortical areas involved in directing eye movements during text reading showed two areas of extra-occipital asymmetry: left > right posterior parietal cortex (PPC), and right > left frontal eye-field (FEF). We used the temporal resolution of repetitive TMS (rTMS) to isolate the contributions of the left and right PPC and FEF to the planning and execution of rightward reading saccades. We present eye-movement data collected during text reading, which involves the initiation and maintenance of a series of saccades (scanpath). rTMS over the left but not right PPC slowed reading speeds for the whole array of words, indicating that this area is involved throughout the scanpath. rTMS over the right but not the left FEF slowed the time to make the first saccade, but only when triggered before the stimuli appeared, demonstrating that the role of this region is in the preparation of the scanpath. Our results are compatible with the hypotheses that the left PPC maintains reading saccades along a line of text while the right FEF is involved in the preparation of the motor plan for the scanpath at the start of each new line of text.     

Frontal and parietal contributions to probabilistic association learning

Neuroimaging studies have shown both dorsolateral prefrontal (DLPFC) and inferior parietal cortex (iPARC) activation during probabilistic association learning. Whether these cortical brain regions are necessary for probabilistic association learning is presently unknown. Participants' ability to acquire probabilistic associations was assessed during disruptive 1 Hz repetitive transcranial magnetic stimulation (rTMS) of the left DLPFC, left iPARC, and sham using a crossover single-blind design. On subsequent sessions, performance improved relative to baseline except during DLPFC rTMS that disrupted the early acquisition beneficial effect of prior exposure. A second experiment examining rTMS effects on task-naive participants showed that neither DLPFC rTMS nor sham influenced naive acquisition of probabilistic associations. A third experiment examining consecutive administration of the probabilistic association learning test revealed early trial interference from previous exposure to different probability schedules. These experiments, showing disrupted acquisition of probabilistic associations by rTMS only during subsequent sessions with an intervening night's sleep, suggest that the DLPFC may facilitate early access to learned strategies or prior task-related memories via consolidation. Although neuroimaging studies implicate DLPFC and iPARC in probabilistic association learning, the present findings suggest that early acquisition of the probabilistic cue-outcome associations in task-naive participants is not dependent on either region.     

Cortical mechanisms for shifting and holding visuospatial attention

Access to visual awareness is often determined by covert, voluntary deployments of visual attention. Voluntary orienting without eye movements requires decoupling attention from the locus of fixation, a shift to the desired location, and maintenance of attention at that location. We used event-related functional magnetic resonance imaging to dissociate these components while observers shifted attention among 3 streams of letters and digits, one located at fixation and 2 in the periphery. Compared with holding attention at the current location, shifting attention between the peripheral locations was associated with transient increases in neural activity in the superior parietal lobule (SPL) and frontal eye fields (FEF), as in previous studies. The supplementary eye fields and separate portions of SPL and FEF were more active for decoupling attention from fixation than for shifting attention to a new location. Large segments of precentral sulcus (PreCS) and posterior parietal cortex (PPC) were more active when attention was maintained in the periphery than when it was maintained at fixation. We conclude that distinct subcomponents of the dorsal frontoparietal network initiate redeployments of covert attention to new locations and disengage attention from fixation, while sustained activity in lateral regions of PPC and PreCS represents sustained states of peripheral attention.     

The role of parietal cortex in awareness of self-generated movements: a transcranial magnetic stimulation study

Awareness of self-generated movements arises from comparing motor plans, and the accompanying (hypothetical) efference copy, with the visual and proprioceptive consequences of movement. Here we used repetitive transcranial magnetic stimulation (rTMS) to investigate the role of a posterior region in the superior parietal lobule (SPL) in this process. Nine healthy volunteers performed a finger extension actively and passively while wearing a CyberGlove; the glove recorded these (actual) finger movements and used this information in real time to move a virtual hand displayed on a computer screen. To assess the participant's awareness of movement onset, we introduced a delay between the onset of the actual and virtual movement (60-270 ms, 30 ms increments); the task was to judge whether the virtual hand movements were delayed relative to the actual hand movements. Low-frequency rTMS (15 min, 0.6 Hz) was applied either over the left SPL or the left temporal cortex (control site) to decrease excitability of these regions and, in turn, test their role in the awareness of self-generated movement. Following the SPL stimulation, participants' assessments of asynchrony were impaired for active but not passive movements. No significant changes were observed after rTMS applied over the control site. We suggest that these findings are consistent with the role of the SPL in evaluating the temporal congruency of peripheral (visual) and central (efference copy) signals associated with self-generated movements. As such, this region may contribute to the sense of 'agency' and its disturbances in disorders such as apraxia and schizophrenia.     

The effect of repetitive transcranial magnetic stimulation on refractory neuropathic pain in spinal cord injury

Objective

To investigate the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) on intractable neuropathic pain in patients with spinal cord injury (SCI).

Design

A single center, prospective, randomized, double-blinded, controlled study.

Setting

SCI rehabilitation unit of university rehabilitation center.

Participants

Seventeen patients with SCI and chronic neuropathic pain who met the inclusion criteria recruited between April 2010 and January 2012.

Interventions

Ten daily treatment sessions of real or sham rTMS (30 trains of 10-Hz stimuli for a duration of 5 seconds; a total of 1500 pulses at intensity equal to 110% of the resting motor threshold) was applied over vertex using a figure-of-8-shaped coil.

Outcome measures

Pain was assessed with visual analog scale (VAS) at baseline and 10 days, 6 weeks and 6 months after the treatment. Patients’ satisfactions obtained using a 5-point Likert scale at 6 months.

Results

Both real and sham rTMS provided a significant reduction in the VAS scores (real rTMS group, P = 0.004; sham rTMS group, P = 0.020). Post hoc analysis revealed the significant difference was at 10 days and 6 weeks compared to baseline in the real rTMS group and only at 10 days compared to baseline in the sham rTMS group. Comparison of VAS scores and patient satisfaction did not show any significant difference at each assessment point (P > 0.05).

Conclusion

Our results demonstrated analgesic effect of rTMS on intractable neuropathic pain in SCI was not superior to placebo. However, middle-term (over 6 weeks) pain relief by rTMS is encouraging and suggests the need for future studies with a larger sample size.     

Flexible, capacity-limited activity of posterior parietal cortex in perceptual as well as visual short-term memory tasks

It has recently been shown, using functional magnetic resonance imaging with a change detection paradigm, that activity in posterior parietal cortex (PPC) correlates with the limited number of objects held in visual short-term memory (VSTM). We replicate this finding and extend it to tasks that use similar stimuli, but without explicit memory requirements. As well as a perceptual task used previously (detecting an item at fixation), 2 additional tasks were designed to increase attentional demands across space (searching for a red item anywhere in the array) and across both space and time (detecting a staggered offset after prolonged viewing of the array). During the VSTM task, a capacity-limited set-size effect was seen in PPC as well as occipital and frontal regions. However, the PPC showed similar activity during 2 of the tasks not requiring VSTM. These findings cannot easily be explained by behavioral performance measures or memory demands alone, suggesting a role of the PPC in processing a limited number of discrete object representations, whether in the current perceptual scene or working memory. The differential influence of item load across perceptual tasks is consistent with task requirements affecting the form of these representations.     

The perceptual and functional consequences of parietal top-down modulation on the visual cortex

The posterior parietal cortex (PPC) has been proposed to play a critical role in exerting top-down influences on occipital visual areas. By inducing activity in the PPC (angular gyrus) using transcranial magnetic stimulation (TMS), and using the phosphene threshold as a measure of visual cortical excitability, we investigated the functional role of this region in modulating the activity of the visual cortex. When triple-pulses of TMS were applied over the PPC unilaterally, the intensity of stimulation required to elicit a phosphene from the visual cortex (area V1/V2) was reduced, indicating an increase in visual cortical excitability. The increased excitability that was observed with unilateral TMS was abolished when TMS was applied over the PPC bilaterally. Our results provide a demonstration of the top-down modulation exerted by the PPC on the visual cortex and show that these effects are subject to interhemispheric competition.     

Impaired visual search in rats reveals cholinergic contributions to feature binding in visuospatial attention

The visual search task established the feature integration theory of attention in humans and measures visuospatial attentional contributions to feature binding. We recently demonstrated that the neuromodulator acetylcholine (ACh), from the nucleus basalis magnocellularis (NBM), supports the attentional processes required for feature binding using a rat digging-based task. Additional research has demonstrated cholinergic contributions from the NBM to visuospatial attention in rats. Here, we combined these lines of evidence and employed visual search in rats to examine whether cortical cholinergic input supports visuospatial attention specifically for feature binding. We trained 18 male Long-Evans rats to perform visual search using touch screen-equipped operant chambers. Sessions comprised Feature Search (no feature binding required) and Conjunctive Search (feature binding required) trials using multiple stimulus set sizes. Following acquisition of visual search, 8 rats received bilateral NBM lesions using 192 IgG-saporin to selectively reduce cholinergic afferentation of the neocortex, which we hypothesized would selectively disrupt the visuospatial attentional processes needed for efficient conjunctive visual search. As expected, relative to sham-lesioned rats, ACh-NBM-lesioned rats took significantly longer to locate the target stimulus on Conjunctive Search, but not Feature Search trials, thus demonstrating that cholinergic contributions to visuospatial attention are important for feature binding in rats.     

Visuo-spatial consciousness and parieto-occipital areas: a high-resolution EEG study

Conscious and unconscious visuo-spatial processes are mainly related to parieto-occipital cortical activation. In this study, the working hypothesis was that a specific pattern of parieto-occipital activation is induced by conscious, as opposed to unconscious, visuo-spatial processes. Electroencephalographic data (128 channels) were recorded in 12 normal adults during a visuo-spatial task. A cue stimulus appeared on the right or the left (equal probability) monitor side for a 'threshold time' inducing approximately 50% of correct recognitions. It was followed (after 2 s) by visual go stimuli at spatially congruent or incongruent positions with reference to the cue location. The left (right) mouse button was clicked if the go stimulus appeared on the left (right) monitor side. Subjects were required to say 'seen' if they had detected the cue stimulus or 'not seen' if they missed it (self-report). 'Seen' and 'not seen' electroencephalographic trials were averaged separately to form visual evoked potentials. Sources of these potentials were estimated by LORETA software. Reaction time to go stimuli was shorter during spatially congruent than incongruent 'seen' trials, possibly due to covert attention on cue for self-report. It was also shorter during spatially congruent than incongruent 'not seen' trials, as an objective sign of unconscious processes. Cue stimulus evoked parieto-occipital potentials which has the same peak latencies in the 'seen' and 'not seen' cases. Sources of these potentials were located in occipital area 19 and parietal area 7. Source strength was significantly stronger in 'seen' than 'not seen' cases at approximately +300 ms post-stimulus. These results may unveil features of parieto-occipital activation accompanying visuo-spatial consciousness.     

Source analysis of event-related cortical activity during visuo-spatial attention

Recordings of event-related potentials (ERPs) were combined with structural and functional magnetic resonance imaging (fMRI) to study the spatio-temporal patterns of cortical activity that underlie visual-spatial attention. Small checkerboard stimuli were flashed in random order to the four quadrants of the visual field at a rapid rate while subjects attended to stimuli in one quadrant at a time. Attended stimuli elicited enhanced ERP components in the latency range 80-200 ms that were co-localized with fMRI activations in multiple extrastriate cortical regions. The earliest ERP component (C1 at 50-90 ms) was unaffected by attention and was localized by dipole modeling to calcarine cortex. A longer latency deflection in the 150-225 ms range that was accounted for by this same calcarine source, however, did show consistent modulation with attention. This late attention effect, like the C1, inverted in polarity for upper versus lower field stimuli, consistent with a neural generator in primary visual cortex (area V1). These results provide support to current hypotheses that spatial attention in humans is associated with delayed feedback to area V1 from higher extrastriate areas that may have the function of improving the salience of stimuli at attended locations.     

Contributions of the PPC to online control of visually guided reaching movements assessed with fMRI-guided TMS

The posterior parietal cortex (PPC) plays an important role in controlling voluntary movements by continuously integrating sensory information about body state and the environment. We tested which subregions of the PPC contribute to the processing of target- and body-related visual information while reaching for an object, using a reaching paradigm with 2 types of visual perturbation: displacement of the visual target and displacement of the visual feedback about the hand position. Initially, functional magnetic resonance imaging (fMRI) was used to localize putative target areas involved in online corrections of movements in response to perturbations. The causal contribution of these areas to online correction was tested in subsequent neuronavigated transcranial magnetic stimulation (TMS) experiments. Robust TMS effects occurred at distinct anatomical sites along the anterior intraparietal sulcus (aIPS) and the anterior part of the supramarginal gyrus for both perturbations. TMS over neighboring sites did not affect online control. Our results support the hypothesis that the aIPS is more generally involved in visually guided control of movements, independent of body effectors and nature of the visual information. Furthermore, they suggest that the human network of PPC subregions controlling goal-directed visuomotor processes extends more inferiorly than previously thought. Our results also point toward a good spatial specificity of the TMS effects.