Neil G. Muggleton

State-dependency in brain stimulation studies of perception and cognition

We address the importance of understanding initial states of neuronal populations and of state-dependent responses in cognitive neuroscience experiments with special emphasis on brain stimulation studies of perception and cognition. The approach we present is based on evidence that behavioural and perceptual effects of transcranial magnetic stimulation (TMS) are determined by initial neural activation state; by systematically manipulating neural activation states before application of TMS, one can selectively target specific, even spatially overlapping neural populations within the affected region. This approach is potentially of great benefit to cognitive neuroscience and remediation programmes as it combines high spatial and functional resolution with the ability to assess causality.

Neural adaptation reveals state-dependent effects of transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is now widely used as a ‘virtual’ lesion paradigm to investigate behavioural functions, but the mechanisms through which it influences neural processing are unclear. To understand the differential effects of TMS on spatially overlapping populations of neurons we manipulated the relative activity levels of visual neurons by adapting subjects to a range of visual stimuli. By applying TMS to the visual cortex representing the central visual field we have shown in two experiments that the behavioural and perceptual effects of TMS depend on the state of adaptation of the neural population stimulated by TMS. Specifically, we have demonstrated that within the stimulated area TMS perceptually facilitates the attributes encoded by the less active neural population. We have demonstrated the generality of this principle for both suprathreshold and subthreshold TMS as well as for colour and orientation‐contingent colour using both subjective reports and psychophsyical measures. These findings can explain how TMS disrupts cognitive functions and therefore have implications for all studies which use TMS to disrupt behaviour.

Unleashing Potential: Transcranial Direct Current Stimulation over the Right Posterior Parietal Cortex Improves Change Detection in Low-Performing Individuals

The limits of human visual short-term memory (VSTM) have been well documented, and recent neuroscientific studies suggest that VSTM performance is associated with activity in the posterior parietal cortex. Here we show that artificially elevating parietal activity via positively charged electric current through the skull can rapidly and effortlessly improve peoples VSTM performance. This artificial improvement, however, comes with an interesting twist: it interacts with peoples natural VSTM capability such that low performers who tend to remember less information benefitted from the stimulation, whereas high performers did not. This behavioral dichotomy is explained by event-related potentials around the parietal regions: low performers showed increased waveforms in N2pc and contralateral delay activity (CDA), which implies improvement in attention deployment and memory access in the current paradigm, respectively. Interestingly, these components are found during the presentation of the test array instead of the retention interval, from the parietal sites ipsilateral to the target location, thus suggesting that transcranial direct current stimulation (tDCS) was mainly improving ones ability to suppress no-change distractors located on the irrelevant side of the display during the comparison stage. The high performers, however, did not benefit from tDCS as they showed equally large waveforms in N2pc and CDA, or SPCN (sustained parietal contralateral negativity), before and after the stimulation such that electrical stimulation could not help any further, which also accurately accounts for our behavioral observations. Together, these results suggest that there is indeed a fixed upper limit in VSTM, but the low performers can benefit from neurostimulation to reach that maximum via enhanced comparison processes, and such behavioral improvement can be directly quantified and visualized by the magnitude of its associated electrophysiological waveforms.

Control of prepotent responses by the superior medial frontal cortex.

The inhibitory control of prepotent action is vital for appropriate behaviour. An example of the importance of such control can be seen in the inhibition of aggressive behavior, deficits in which may have broader consequences for society. Many studies have related lesions or the under-development of the prefrontal cortex to inefficiency of inhibitory control. Here we used transcranial magnetic stimulation and a stop-signal task, which occasionally requires the inhibition of a prepotent motor response, to investigate the role of pre-supplementary motor area (Pre-SMA) in inhibitory control. While no effects were seen on the ability to generate responses, TMS delivered over the Pre-SMA disrupted the ability to respond to a stop signal. These results are the first to establish a casual link between Pre-SMA and inhibitory control in normal subjects. The understanding of the underlying mechanisms of inhibitory control may lead to clearer understanding of the neural basis of inappropriate behaviour.

TMS over right posterior parietal cortex induces neglect in a scene-based frame of reference

Although damage to right posterior parietal cortex (RPPC) produces bias in line bisection, Karnath et al. [Karnath, H.-O., Berger, M. F., Küker, W., & Rorden, C. (2004). The anatomy of spatial neglect based on voxelwise statistical analysis: A study of 140 patients. Cerebral Cortex, 14, 1164-1172] claim that it plays little role in spatial neglect, which is better measured by target cancellation. We used a detection task (approximating cancellation in requiring detection) to investigate this claim by compromising the parietal cortex with transcranial magnetic stimulation (TMS). Two outline shapes, one on each side of fixation, were briefly displayed before a mask. The target was a discontinuity in the left or right of the outline of one of these perceptual objects. Subjects indicated position or absence of target as fast as possible. Stimulus-mask onset asynchrony was adjusted individually to yield 75% detection. TMS was delivered over left posterior parietal cortex (LPPC), RPPC and Vertex, with Sham TMS over RPPC as a baseline control. Target detection was near ceiling and fastest at central positions and worst and slowest at the far right. Detection was significantly reduced at the far left position by TMS over RPPC. No other effects were obtained and latency was not affected by TMS. Disruption of RPPC by TMS does produce left neglect as measured by detection. Given the pattern of performance and since it was disrupted on one side of the display rather than on one side of each shape, attention and neglect were in a scene-based rather than object-based reference frame.

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.

Segregation of visual selection and saccades in human frontal eye fields.

The premotor theory of attention suggests that target processing and generation of a saccade to the target are interdependent. Temporally precise transcranial magnetic stimulation (TMS) was delivered over the human frontal eye fields, the area most frequently associated with the premotor theory in association with eye movements, while subjects performed a visually instructed pro-/antisaccade task. Visual analysis and saccade preparation were clearly separated in time, as indicated by 2 distinct time points of TMS delivery that resulted in elevated saccade latencies. These results show that visual analysis and saccade preparation, although frequently enacted together, are dissociable processes.

Neural activation state determines behavioral susceptibility to modified theta burst transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) allows one to investigate the effects of temporary interference of neural processing in neurologically intact subjects. In a previous study [J. Silvanto et al. (2007) Eur. J. Neurosci., 25, 1874–1881] we found that online TMS perceptually facilitates the attributes encoded by the least active neural populations. The objective of the present experiment was to extend this work to determine whether such state‐dependent effects can be observed when offline high‐frequency TMS is applied to suppress neural activity. The activity levels of direction‐selective neural populations in the V1/V2 region were modulated by asking subjects to passively view either leftward or rightward motion during offline TMS. In a subsequent motion direction‐discrimination task, their ability to discriminate motion direction was dependent on the type of motion they had passively viewed during offline TMS: detection of the congruent direction (i.e. direction viewed during offline TMS) was unaffected, whereas detection of the incongruent direction (i.e. opposite direction to the one viewed during offline TMS) was impaired. As the activity level of neurons tuned to the incongruent direction was presumably lower during the TMS than of those tuned to the congruent direction, this behavioral result demonstrates that the offline TMS preferentially suppressed attributes encoded by the least active neural populations. In contrast to direction discrimination, motion detection was not impaired in a direction‐specific manner. This shows that the requirements of the psychophysical task, in conjunction with the relative activity states of neuronal populations when TMS is applied, can be used to selectively interfere with overlapping neuronal populations.

Effects of tms over premotor and superior temporal cortices on biological motion perception

Using MRI-guided off-line TMS, we targeted two areas implicated in biological motion processing: ventral premotor cortex (PMC) and posterior STS (pSTS), plus a control site (vertex). Participants performed a detection task on noise-masked point-light displays of human animations and scrambled versions of the same stimuli. Perceptual thresholds were determined individually. Performance was measured before and after 20 sec of continuous theta burst stimulation of PMC, pSTS, and control (each tested on different days). A matched nonbiological object motion task (detecting point-light displays of translating polygons) served as a further control. Data were analyzed within the signal detection framework. Sensitivity (d′) significantly decreased after TMS of PMC. There was a marginally significant decline in d′ after TMS of pSTS but not of control site. Criterion (response bias) was also significantly affected by TMS over PMC. Specifically, subjects made significantly more false alarms post-TMS of PMC. These effects were specific to biological motion and not found for the nonbiological control task. To summarize, we report that TMS over PMC reduces sensitivity to biological motion perception. Furthermore, pSTS and PMC may have distinct roles in biological motion processing as behavioral performance differs following TMS in each area. Only TMS over PMC led to a significant increase in false alarms, which was not found for other brain areas or for the control task. TMS of PMC may have interfered with refining judgments about biological motion perception, possibly because access to the perceivers own motor representations was compromised.

Double Dissociation of Format-Dependent and Number-Specific Neurons in Human Parietal Cortex

Based on neuroimaging methods, it is a commonly held view that numerical representation in the human parietal lobes is format independent. We used a transcranial magnetic stimulation adaptation paradigm to examine the existence of functionally segregated overlapping populations of neurons for different numerical formats and to reveal how numerical information is encoded and represented. Based on 2 experiments, we found that right parietal lobe stimulation showed a dissociation between digits and verbal numbers, whereas the left parietal lobe showed a double dissociation between the different numerical formats. Further analysis and modeling also excluded pre- or postrepresentational components as the source of the current effects. These results demonstrate that both parietal lobes are equipped with format-dependent neurons that encode quantity.