Site-Dependent Effects of tDCS Uncover Dissociations in the Communication Network Underlying the Processing of Visual Search

BackgroundThe right posterior parietal cortex (rPPC) and the right frontal eye field (rFEF) form part of a network of brain areas involved in orienting spatial attention. Previous studies using transcranial magnetic stimulation (TMS) have demonstrated that both areas are critically involved in the processing of conjunction visual search tasks, since stimulation of these sites disrupts performance.ObjectiveThis study investigated the effects of long term neuronal modulation to rPPC and rFEF using transcranial direct current stimulation (tDCS) with the aim of uncovering sharing of these resources in the processing of conjunction visual search tasks.MethodsParticipants completed four blocks of conjunction search trials over the course of 45 min. Following the first block they received 15 min of either cathodal or anodal stimulation to rPPC or rFEF, or sham stimulation.ResultsA significant interaction between block and stimulation condition was found, indicating that tDCS caused different effects according to the site (rPPC or rFEF) and type of stimulation (cathodal, anodal, or sham). Practice resulted in a significant reduction in reaction time across the four blocks in all conditions except when cathodal tDCS was applied to rPPC.ConclusionsThe effects of cathodal tDCS over rPPC are subtler than those seen with TMS, and no effect of tDCS was evident at rFEF. This suggests that rFEF has a more transient role than rPPC in the processing of conjunction visual search and is robust to longer-term methods of neuro-disruption. Our results may be explained within the framework of functional connectivity between these, and other, areas.     

Predictability of saccadic behaviors is modified by transcranial magnetic stimulation over human posterior parietal cortex

Predictability in the visual environment provides a powerful cue for efficient processing of scenes and objects. Recently, studies have suggested that the directionality and magnitude of saccade curvature can be informative as to how the visual system processes predictive information. The present study investigated the role of the right posterior parietal cortex (rPPC) in shaping saccade curvatures in the context of predictive and non-predictive visual cues. We used an orienting paradigm that incorporated manipulation of target location predictability and delivered transcranial magnetic stimulation (TMS) over rPPC. Participants were presented with either an informative or uninformative cue to upcoming target locations. Our results showed that rPPC TMS generally increased saccade latency and saccade error rates. Intriguingly, rPPC TMS increased curvatures away from the distractor only when the target location was unpredictable and decreased saccadic errors towards the distractor. These effects on curvature and accuracy were not present when the target location was predictable. These results dissociate the strong contingency between saccade latency and saccade curvature and also indicate that rPPC plays an important role in allocating and suppressing attention to distractors when the target demands visual disambiguation. Furthermore, the present study suggests that, like the frontal eye fields, rPPC is critically involved in determining saccade curvature and the generation of saccadic behaviors under conditions of differing target predictability.     

The neural basis of the Enigma illusion: a transcranial magnetic stimulation study

The aim of this study was to test the role of the visual primary (V1) and the middle temporal area (V5/MT) in the illusory motion perception evoked by the Enigma figure. The Enigma figure induces a visual illusion that is characterized by apparent rotatory motion in the presence of a static figure. By means of repetitive transcranial magnetic stimulation (rTMS) we show that V5/MT is causally linked to the illusory perception of motion. When rTMS was applied bilaterally over V5/MT just prior to presentation of the Enigma figure, the perception of illusory motion was disrupted for approximately 400 ms resulting in a delayed illusion onset. In contrast, rTMS applied over V1 did not have any effect on the illusory perception of motion. These results show that V5/MT, a visual cortical area associated with real motion perception, is also important for the perception of illusory motion, while V1 appears not to be functionally involved in illusory motion perception.     

Hemispheric differences in frontal and parietal influences on human occipital cortex: direct confirmation with concurrent TMS-fMRI

We used concurrent TMS-fMRI to test directly for hemispheric differences in causal influences of the right or left fronto-parietal cortex on activity (BOLD signal) in the human occipital cortex. Clinical data and some behavioral TMS studies have been taken to suggest right-hemisphere specialization for top-down modulation of vision in humans, based on deficits such as spatial neglect or extinction in lesioned patients, or findings that TMS to right (vs. left) fronto-parietal structures can elicit stronger effects on visual performance. But prior to the recent advent of concurrent TMS and neuroimaging, it was not possible to directly examine the causal impact of one (stimulated) brain region upon others in humans. Here we stimulated the frontal or intraparietal cortex in the left or right hemisphere with TMS, inside an MR scanner, while measuring with fMRI any resulting BOLD signal changes in visual areas V1-V4 and V5/MT+. For both frontal and parietal stimulation, we found clear differences between effects of right- versus left-hemisphere TMS on activity in the visual cortex, with all differences significant in direct statistical comparisons. Frontal TMS over either hemisphere elicited similar BOLD decreases for central visual field representations in V1-V4, but only right frontal TMS led to BOLD increases for peripheral field representations in these regions. Hemispheric differences for effects of parietal TMS were even more marked: Right parietal TMS led to strong BOLD changes in V1-V4 and V5/MT+, but left parietal TMS did not. These data directly confirm that the human frontal and parietal cortex show right-hemisphere specialization for causal influences on the visual cortex.     

Increasing generosity by disrupting prefrontal cortex

Recent research suggests that prosocial outcomes in sharing games arise from prefrontal control of self-maximizing impulses. We used continuous theta burst stimulation (cTBS) to disrupt the functioning of two prefrontal areas, the right dorsolateral prefrontal cortex (DLPFC) and the dorsomedial prefrontal cortex (DMPFC). We used cTBS in the right MT/V5, as a control area. We then tested subjects’ prosocial inclinations with an unsupervised Dictator Game in which they allocated real money anonymously between themselves and low and high socioeconomic status (SES) players. cTBS over the two prefrontal sites made subjects more generous compared to MT/V5. More specifically, cTBS over DLPFC increased offers to high-SES players, while cTBS over DMPFC caused increased offers to low-SES players. These data, the first to demonstrate an effect of disruptive neuromodulation on costly sharing, suggest that DLPFC and MPFC exert inhibitory control over prosocial inclinations during costly sharing, though they may do so in different ways. DLPFC may implement contextual control, while DMPFC may implement a tonic form of control. This study demonstrates that humans’ prepotent inclination is toward prosocial outcomes when cognitive control is reduced, even when prosocial decisions carry no strategic benefit and concerns for reputation are minimized.     

Involvement of V5/MT+ in object substitution masking: evidence from repetitive transcranial magnetic stimulation

The visibility of a briefly presented target can be reduced by a subsequent weak mask that does not touch it, when the target is encoded in low spatiotemporal resolution. This phenomenon, called object substitution masking, has recently been proposed to reflect information updating in object-level representation, with perception of the target and the mask belonging to a single object through apparent motion. We investigated this issue by applying repetitive transcranial magnetic stimulation over V5/MT+, specialized in visual motion processing. The transient functional disruption of V5/MT+ produced by repetitive transcranial magnetic stimulation attenuated object substitution masking, while sham stimulation did not. Our results suggest that object substitution masking is mediated by normal functioning of V5/MT+. We conclude that repetitive transcranial magnetic stimulation of V5/MT+ impaired perceived object continuity and reduced object substitution masking accordingly.     

Human dorsolateral prefrontal cortex is involved in visual search for conjunctions but not features: A theta TMS study

Functional neuroimaging studies have shown that the detection of a target defined by more than one feature (for example, a conjunction of colour and orientation) amongst distractors is associated with the activation of a network of brain areas. Dorsolateral prefrontal cortex (DLPFC), along with areas such as the frontal eye fields (FEF) and posterior parietal cortex (PPC), is a component of this network. While transcranial magnetic stimulation (TMS) had shown that both FEF and PPC are necessary for, and not just correlated with, successful conjunction search, this is not the case for DLPFC. To test the hypothesis that this area is also necessary for efficient conjunction search, TMS was applied over DLPFC and the effects on conjunction and feature (in this case colour) search performance compared with those when TMS was delivered over area MT/V5 and a vertex control stimulation condition. DLPFC TMS impaired performance on the conjunction search task but was without effect on feature search, similar to findings when TMS is delivered over PPC or FEF. Vertex TMS had no effects whereas MT/V5 TMS significantly improved performance with a time course that may indicate that this was due to modulation of V4 activity. These findings illustrate that, like FEF and PPC, DLPFC is necessary for fully effective conjunction visual search performance.     

Making the blindsighted see

A lesion of striate cortex, area V1, produces blindness in the retinotopically corresponding part of the visual field, although in some cases visual abilities in the blind field remain that are paradoxically devoid of conscious visual percepts (“blindsight”). Here we demonstrate that the blindsight subject GY can experience visual sensations of phosphenes in his blind field induced by transcranial magnetic stimulation (TMS). Such blind field percepts could only be induced when stimulation was applied bilaterally, i.e. over GY's area V5/MT in both hemispheres. Consistent with an earlier report [Cowey, A., & Walsh, V. (2000). Magnetically induced phosphenes in sighted, blind and blindsighted observers. Neuroreport, 11, 3269–3273], GY never experienced phosphenes when stimulation was restricted to his ipsilesional V5/MT. To the best of our knowledge this is the first time GY has experienced visual qualia in his blind hemifield. The present report characterizes the necessary conditions for such conscious experience in his hemianopic visual field and interprets them as demonstrating that only via a contribution from GY's intact hemisphere can activation in the damaged hemisphere reach visual awareness.     

Effects of theta burst stimulation protocols on phosphene threshold.

OBJECTIVE: We investigated the effects on occipital cortex, of two newly developed methods of repetitive transcranial magnetic stimulation (rTMS): continuous and intermittent theta burst stimulation (cTBS and iTBS), that lead to long lasting changes in excitability when applied over primary motor cortex. METHODS: Phosphene threshold to a single TMS pulse was measured before and after application of either continuous or intermittent theta burst stimulation (cTBS/iTBS; 600 total pulses at 80% phosphene threshold). RESULTS: In our cohort, cTBS increased phosphene threshold by an average of 10%. In contrast, iTBS, which transiently increases motor cortex excitability, had no effect on phosphene threshold. CONCLUSIONS: cTBS can be applied successfully to non-motor areas of cortex, but iTBS may need modification to produce maximal effects. SIGNIFICANCE: cTBS maybe a new useful tool in disorders characterized by an abnormal state of activity of the visual cortex.     

Investigating visual motion perception using the transcranial magnetic stimulation-adaptation paradigm

The state-dependency approach of transcranial magnetic stimulation (TMS) enables differential stimulation of functionally distinct neural populations within the affected region of cortex. Here we tested the validity of a paradigm based on state-dependency, the TMS-adaptation paradigm, in the context of visual motion perception. Visual adaptation was used to induce an activity imbalance in direction-selective neurons in the visual cortex, after which participants performed a motion direction discrimination task. When TMS was applied over the motion-selective area V5/MT before each experimental trial, the detection of the direction encoded by the adapted neurons was facilitated relative to the direction encoded by the nonadapted neurons. This finding demonstrates, in the domain of visual motion detection, the state-dependency of TMS effects and the validity of the TMS-adaptation paradigm.     

Repetitive transcranial magnetic stimulation of human area MT/V5 disrupts perception and storage of the motion aftereffect

Following adaptation to a moving stimulus, the introduction of a stationary pattern creates the illusion of motion. This phenomenon, known as the motion aftereffect (MAE), can be delayed by placing a blank storage interval between the adapting and test stimuli. Human motion selective area MT/V5 has been proposed as the likely neural origin of MAEs. To examine the role of MT/V5 in perceiving and storing MAEs, we applied repetitive transcranial magnetic stimulation (rTMS) to this area during a 10 s storage interval and while subjects perceived illusory motion. Our results show that rTMS disrupts perception of the MAE when it is delivered in the early parts of the storage period and when it is applied during the perceptual MAE itself. Stimulation of control regions corresponding to V1 or Cz did not affect the MAE. In addition, magnetic stimulation of dorsolateral prefrontal and posterior parietal cortices did not disrupt MAE perception. These data provide experimental support for the notion that MT/V5 subserves perception and storage of the motion aftereffect.     

Effects of continuous theta burst transcranial magnetic stimulation on cortical excitability in patients with idiopathic generalized epilepsy

IntroductionTranscranial magnetic stimulation (TMS) is a noninvasive technique for investigating cortical physiologic functions in the brain. In this study, the effects of continuous theta burst stimulation (cTBS) on motor evoked potential (MEP) parameters in patients with idiopathic generalized epilepsy (IGE) were investigated.Materials and methodsFifteen patients with IGE were included. Motor threshold (MT) and cortical silent period (CSP) were determined before cTBS application. Next, cTBS was applied to the dominant (left) hemisphere M1 hand area as the first application. After 1 day, cTBS was applied first to the left M1 hand area and then to the right lateral cerebellar area as the second application. Parameters were again determined after the applications.ResultsThere was no difference in resting MT values before and after cTBS application (p > 0.05). Although CSP increased after stimulation (p < 0.05), it was not significantly different between applications (p > 0.05).ConclusionFor patients with epilepsy, cTBS is a safe technique when applied at a low intensity. The inhibitory effect of cTBS, a noninvasive technique, on cortical excitability in patients with IGE was determined using MEP parameters. The effect lasted at least 1 h. To our knowledge, this is the first study to assess the effect of cTBS on cortical excitability in patients with IGE. Our findings indicate that cTBS decreases cortical excitability in patients with IGE.     

Direct current stimulation over MT+/V5 modulates motion aftereffect in humans

While there is strong evidence for the central role of the human MT+/V5 in motion processing, its involvement in motion adaptation is still the subject of debate. We used transcranial direct current stimulation (tDCS) to test whether MT+/V5 is part of the neural network involved in the long-term adaptation-induced motion after-effect in humans. It was found that both cathodal and anodal stimulation over MT+/V5 resulted in a significant reduction of the perceived motion after-effect duration, but had no effect on performance in a luminance-change-detection task used to determine attentional load during adaptation. Our control experiment excluded the possibility that the observed MT+/V5 stimulation effects were due to a diffused modulation of the early cortical areas, i.e. by the stimulation applied over MT+/V5. These results provide evidence that external modulation of neural excitability in human MT+/V5 affects the strength of perceived motion after-effect and support the involvement of MT+/V5 in motion adaptation processes.     

The fastest (and simplest), the earliest: the locus of processing of rapid forms of motion aftereffect

Adaptation to directional motion has been shown to bias the perceived direction of a subsequently presented stationary or flickering test stimulus toward the opposite direction with respect to that of adaptation. This phenomenon, called motion aftereffect, is usually generated with adaptation periods of tens of seconds or minutes and has been shown to depend upon the functional integrity of visual area V5/MT. Rapid forms of MAE, arising and decaying within half a second (rMAE), can also be generated with sub-second adaptation durations. In order to investigate the neural substrate underlying the rMAE, repetitive transcranial magnetic stimulation (rTMS) has been used just after the adaptation stimulus over areas V1/V2, V5/MT, or over the vertex. Results showed that, besides some reduction in strength of the rMAE when rTMS was delivered over V5/MT, it was maximally disrupted when stimulation was delivered over early visual areas V1/V2. This is the first study where a causal role of early visual cortices in MAE is demonstrated. Moreover, this finding supports the existence of multiple loci along the visual stream in which gain control takes place and generates the MAE as a byproduct. The specific locus is likely to depend on the specific stimulus used.     

Insights on the neural basis of motor plasticity induced by theta burst stimulation from TMS–EEG

Transcranial magnetic stimulation (TMS) is a useful tool to induce and measure plasticity in the human brain. However, the cortical effects are generally indirectly evaluated with motor‐evoked potentials (MEPs) reflective of modulation of cortico‐spinal excitability. In this study, we aim to provide direct measures of cortical plasticity by combining TMS with electroencephalography (EEG). Continuous theta‐burst stimulation (cTBS) was applied over the primary motor cortex (M1) of young healthy adults, and we measured modulation of (i) MEPs, (ii) TMS‐induced EEG evoked potentials (TEPs), (iii) TMS‐induced EEG synchronization and (iv) eyes‐closed resting EEG. Our results show the expected cTBS‐induced decrease in MEP size, which we found to be paralleled by a modulation of a combination of TEPs. Furthermore, we found that cTBS increased the power in the theta band of eyes‐closed resting EEG, whereas it decreased single‐pulse TMS‐induced power in the theta and alpha bands. In addition, cTBS decreased the power in the beta band of eyes‐closed resting EEG, whereas it increased single‐pulse TMS‐induced power in the beta band. We suggest that cTBS acts by modulating the phase alignment between already active oscillators; it synchronizes low‐frequency (theta and/or alpha) oscillators and desynchronizes high‐frequency (beta) oscillators. These results provide novel insight into the cortical effects of cTBS and could be useful for exploring cTBS‐induced plasticity outside of the motor cortex.     

Disruptions to human speed perception induced by motion adaptation and transcranial magnetic stimulation

To investigate the underlying nature of the effects of transcranial magnetic stimulation (TMS) on speed perception, we applied repetitive TMS (rTMS) to human V5/MT+ following adaptation to either fast‐ (20 deg/s) or slow (4 deg/s)‐moving grating stimuli. The adapting stimuli induced changes in the perceived speed of a standard reference stimulus moving at 10 deg/s. In the absence of rTMS, adaptation to the slower stimulus led to an increase in perceived speed of the reference, whilst adaptation to the faster stimulus produced a reduction in perceived speed. These induced changes in speed perception can be modelled by a ratio‐taking operation of the outputs of two temporally tuned mechanisms that decay exponentially over time. When rTMS was applied to V5/MT+ following adaptation, the perceived speed of the reference stimulus was reduced, irrespective of whether adaptation had been to the faster‐ or slower‐moving stimulus. The fact that rTMS after adaptation always reduces perceived speed, independent of which temporal mechanism has undergone adaptation, suggests that rTMS does not selectively facilitate activity of adapted neurons but instead leads to suppression of neural function. The results highlight the fact that potentially different effects are generated by TMS on adapted neuronal populations depending upon whether or not they are responding to visual stimuli.     

Restoration of motor inhibition through an abnormal premotor‐motor connection in dystonia

To clarify the rationale for using rTMS of dorsal premotor cortex (PMd) to treat dystonia, we examined how the motor system reacts to an inhibitory form of rTMS applied to the PMd in healthy subjects and in a group of patients with focal hand dystonia and DYT1 gene carriers. Continuous theta burst transcranial magnetic stimulation (cTBS) with 300 and 600 pulses (cTBS300 and cTBS600) was applied to PMd, and its after‐effects were quantified by measuring the amplitude of MEPs evoked by single pulse transcranial magnetic stimulation (TMS) over the primary motor cortex (M1), short interval intracortical inhibition/facilitation (SICI/ICF) within M1, the third phase of spinal reciprocal inhibition (RI), and writing tests. In addition, in DYT1 gene carriers, the effects of cTBS300 over M1 and PMd on MEPs were studied in separate experiments. In healthy subjects, cTBS300 and cTBS600 over PMd suppressed MEPs for 30 min or more and cTBS600 decreased SICI and RI. In contrast, neither form of cTBS over PMd had any significant effect on MEPs, while cTBS600 increased effectiveness of SICI and RI and improved writing in patients with writer's cramp. NMDYT1 had a normal response to cTBS300 over left PMd. We suggest that the reduced PMd to M1 interaction in dystonic patients is likely to be due to reduced excitability of PMd‐M1 connections. The possible therapeutic effects of premotor rTMS may therefore involve indirect effects of PMd on SICI and RI, which this study has shown can be normalised by cTBS. © 2010 Movement Disorder Society     

No correlation between moving phosphene and motor thresholds: a transcranial magnetic stimulation study

The aim of this study was to investigate the temporal stability of moving phosphenes and to assess whether moving phosphene thresholds (PTs) correlate with motor thresholds (MTs). Small moving sensations, so-called moving phosphenes, are perceived when V5, an area important for visual motion analysis, is stimulated by transcranial magnetic stimulation (TMS). However, it is still a matter of debate if V5 phosphenes are stable sensations across measurements and if they are a reasonable index of the cortical excitability of V5. Currently, MT is more commonly used as an index of global cortical excitability. However, previous studies have indicated that stationary PTs are suitable alternatives when the primary visual cortex is stimulated by TMS. Using paired-pulse TMS, stationary and moving PTs and applying single pulse TMS, MTs were measured in 11 subjects. PTs were retested in nine subjects 5-7 days later. Stationary and moving PTs were stable within subjects across the two sessions and showed a high inter-correlation. Conversely, PTs and MTs did not correlate. Our results are in agreement with previous studies showing that excitatory measurements of one specific cortex cannot be generalized to the excitability of the whole cortex. Thus, we propose specific measures for cortices of interest: PT for visual experiments and MT for motor experiments.     

Temporal characteristics of global motion processing revealed by transcranial magnetic stimulation

The ability to detect the motion of objects is critical to survival, and understanding the cortical mechanisms involved in this process remains a key challenge in sensory neuroscience. A relatively new approach to this problem is to temporarily disrupt processing at specific cortical sites and measure the behavioural consequences. Several previous studies have shown that transcranial magnetic stimulation (TMS) of human visual area V5/MT disrupts global motion perception, but reports vary widely in the timescale of this effect. To resolve this issue we employed psychophysical techniques to investigate how discrimination of translational, rotational and radial global motion is affected by TMS. Prior to applying TMS we established baseline coherence thresholds for global motion perception. Adopting each observer’s coherence level at threshold we examined how TMS delivered to V5/MT modulated performance. Importantly, we measured the influence of single‐pulse TMS over a broad temporal range to reveal the fine temporal structure of the disruption profile for global motion perception. Results show that the disruption profile consisted of two distinct epochs during which global direction judgments were reliably impaired, separated by an interval in which performance was unaffected. The bimodal nature of the distribution profiles is consistent with feedforward and feedback processing between visual areas mediating global motion processing. We present a novel quantitative model that characterizes the contribution of each process to visual motion perception.     

Cerebellar Control on Prefrontal-Motor Connectivity During Movement Inhibition

Converging evidence suggests a crucial role of right inferior frontal gyrus (r-IFG) and right pre-supplementary motor area (r-preSMA) in movement inhibition control. The present work was aimed to investigate how the effective connectivity between these prefrontal areas and the primary motor cortex could change depending on the activity of the cerebellar cortex. Paired transcranial magnetic stimulation (TMS) was delivered in healthy subjects over the r-IFG/left primary motor area (l-M1) and over r-preSMA/l-M1 before (100 ms after the fixation cross onset) and 50, 75, 100, 125, and 150 ms after the presentation of a Go/NoGo visual cue establishing the specific time course and the causal interactions of these regions in relation to l-M1 as measured by motor evoked potentials (MEPs). The same paired-pulse protocol was applied following sham or real cerebellar continuous theta burst stimulation (cTBS). Following sham cTBS, for NoGo trials only, MEPs collected showed the expected pattern of activation for both r-IFG-l-M1 and r-preSMA-l-M1 connectivity, characterized by peaks of increased and decreased MEP amplitude regularly repeated every 50 ms. Following cerebellar cTBS, this pattern of activation related to NoGo trials was modified selectively for the r-IFG-M1 but not for r-preSMA-M1 connection. A common monitoring action of r-IFG and r-preSMA in inhibitory control was confirmed. The effects of cerebellar cTBS showed a specific interaction between cerebellum and r-IFG activity during the inhibitory process.