Juha Silvanto

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.

State-Dependency of Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS), a tool that allows noninvasive modulation of cortical neural activity, has become an important tool in cognitive neuroscience and is being increasingly explored in neurotherapeutics. Amongst the factors that are likely to influence its efficacy, the importance of the baseline cortical activation state on the impact of TMS has not received much attention. However, this state-dependency is important as the neural impact of any external stimulus represents an interaction with the ongoing brain activity at the time of stimulation. The effects of any external stimulus are therefore not only determined by the properties of that stimulus but also by the activation state of the brain. Here we review the existing evidence on the state-dependency of TMS and propose how its systematic study can provide unique insights into brain function and significantly enhance the effectiveness of TMS in investigations on the neural basis of perception and cognition. We also describe novel approaches based on this state-dependency which can be used to investigate the properties of distinct neural subpopulations within the stimulated region. Furthermore, we discuss how state-dependency can explain the functional mechanisms through which TMS impairs perception and behavior.

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.

Stochastic Resonance Effects Reveal the Neural Mechanisms of Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a popular method for studying causal relationships between neural activity and behavior. However, its mode of action remains controversial, and so far there is no framework to explain its wide range of facilitatory and inhibitory behavioral effects. While some theoretical accounts suggest that TMS suppresses neuronal processing, other competing accounts propose that the effects of TMS result from the addition of noise to neuronal processing. Here we exploited the stochastic resonance phenomenon to distinguish these theoretical accounts and determine how TMS affects neuronal processing. Specifically, we showed that online TMS can induce stochastic resonance in the human brain. At low intensity, TMS facilitated the detection of weak motion signals, but with higher TMS intensities and stronger motion signals, we found only impairment in detection. These findings suggest that TMS acts by adding noise to neuronal processing, at least in an online TMS protocol. Importantly, such stochastic resonance effects may also explain why TMS parameters that under normal circumstances impair behavior can induce behavioral facilitations when the stimulated area is in an adapted or suppressed state.

Working memory without consciousness

Working memory allows individuals to maintain information in the focus of the minds eye in the service of goal-directed behavior. Current psychological theories (for example, Baddeleys influential model of working memory) [1], computational models [2] and neurobiological accounts of working memory are based on the assumption that working memory operates on consciously represented information. Models of the capacity limits of working memory [3] are silent on this issue. While there has been some suggestion that working memory may be engaged by incidental exposure to visible items [4], current understanding indicates that the encoding of information in working memory, maintenance, retrieval and use in decision making of working memory operate on the contents of consciousness. But no study to date has investigated working memory processing for unconscious information. Here we show that observers can encode a subliminal orientation cue, maintain it ‘on-line’ even in the presence of visible distracters, and perform above chance in subsequent explicit discrimination, namely, whether a supraliminal orientation probe was tilted clockwise or counter-clockwise relative to the earlier unconscious cue. Our findings challenge the currently held view that working memory processes are contingent on conscious awareness.

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.

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.

Information-Based Approaches of Noninvasive Transcranial Brain Stimulation

Progress in cognitive neuroscience relies on methodological developments to increase the specificity of knowledge obtained regarding brain function. For example, in functional neuroimaging the current trend is to study the type of information carried by brain regions rather than simply compare activation levels induced by task manipulations. In this context noninvasive transcranial brain stimulation (NTBS) in the study of cognitive functions may appear coarse and old fashioned in its conventional uses. However, in their multitude of parameters, and by coupling them with behavioral manipulations, NTBS protocols can reach the specificity of imaging techniques. Here we review the different paradigms that have aimed to accomplish this in both basic science and clinical settings and follow the general philosophy of information-based approaches.

Improved Motion Perception and Impaired Spatial Suppression following Disruption of Cortical Area MT/V5

As stimulus size increases, motion direction of high-contrast patterns becomes increasingly harder to perceive. This counterintuitive behavioral result, termed “spatial suppression,” is hypothesized to reflect center–surround antagonism—a receptive field property ubiquitous in sensory systems. Prior research proposed that spatial suppression of motion signals is a direct correlate of center–surround antagonism within cortical area MT. Here, we investigated whether human MT/V5 is indeed causally involved in spatial suppression of motion signals. The key assumption is that a disruption of neural mechanisms that play a critical role in spatial suppression could allow these normally suppressed motion signals to reach perceptual awareness. Thus, our hypothesis was that a disruption of MT/V5 should weaken spatial suppression and, consequently, improve motion perception of large, moving patterns. To disrupt MT/V5, we used offline 1 Hz transcranial magnetic stimulation (TMS)—a method that temporarily attenuates normal functioning of the targeted cortex. Early visual areas were also targeted as a control site. The results supported our hypotheses and showed that disruption of MT/V5 improved motion discrimination of large, moving stimuli, presumably by weakening surround suppression strength. This effect was specific to MT/V5 stimulation and contralaterally presented stimuli. Evidently, the critical neural constraints limiting motion perception of large, high-contrast stimuli involve MT/V5. Additionally, our findings mimic spatial suppression deficits that are observed in several patient populations and implicate impaired MT/V5 processes as likely neural correlates for the reported perceptual abnormalities in the elderly, patients with schizophrenia and those with a history of depression.

Reappraising the relationship between working memory and conscious awareness.

Classically, the operation of working memory (WM) has been strongly coupled with conscious states; it is thought that WM operates on conscious input and that we are conscious of the contents and operations of WM. Here, we re-evaluate the relationship between WM and conscious awareness in light of current data and question the views that awareness is mandatory for the operation of WM and that WM contents are necessarily linked to experiential states that are consciously accessible for perceptual report. We propose a novel framework for the relationship between WM and conscious awareness.