Olivia Carter

Quantitative Review Finds No Evidence of Cognitive Effects in Healthy Populations From Single-session Transcranial Direct Current Stimulation (tDCS)

BACKGROUND Over the last 15-years, transcranial direct current stimulation (tDCS), a relatively novel form of neuromodulation, has seen a surge of popularity in both clinical and academic settings. Despite numerous claims suggesting that a single session of tDCS can modulate cognition in healthy adult populations (especially working memory and language production), the paradigms utilized and results reported in the literature are extremely variable. To address this, we conduct the largest quantitative review of the cognitive data to date. METHODS Single-session tDCS data in healthy adults (18-50) from every cognitive outcome measure reported by at least two different research groups in the literature was collected. Outcome measures were divided into 4 broad categories: executive function, language, memory, and miscellaneous. To account for the paradigmatic variability in the literature, we undertook a three-tier analysis system; each with less-stringent inclusion criteria than the prior. Standard mean difference values with 95% CIs were generated for included studies and pooled for each analysis. RESULTS Of the 59 analyses conducted, tDCS was found to not have a significant effect on any - regardless of inclusion laxity. This includes no effect on any working memory outcome or language production task. CONCLUSION Our quantitative review does not support the idea that tDCS generates a reliable effect on cognition in healthy adults. Reasons for and limitations of this finding are discussed. This work raises important questions regarding the efficacy of tDCS, state-dependency effects, and future directions for this tool in cognitive research.

Evidence that transcranial direct current stimulation (tDCS) generates little-to-no reliable neurophysiologic effect beyond MEP amplitude modulation in healthy human subjects: A systematic review

BACKGROUND Transcranial direct current stimulation (tDCS) is a form of neuromodulation that is increasingly being utilized to examine and modify a number of cognitive and behavioral measures. The theoretical mechanisms by which tDCS generates these changes are predicated upon a rather large neurophysiological literature. However, a robust systematic review of this neurophysiological data has not yet been undertaken. METHODS tDCS data in healthy adults (18-50) from every neurophysiological outcome measure reported by at least two different research groups in the literature was collected. When possible, data was pooled and quantitatively analyzed to assess significance. When pooling was not possible, data was qualitatively compared to assess reliability. RESULTS Of the 30 neurophysiological outcome measures reported by at least two different research groups, tDCS was found to have a reliable effect on only one: MEP amplitude. Interestingly, the magnitude of this effect has been significantly decreasing over the last 14 years. CONCLUSION Our systematic review does not support the idea that tDCS has a reliable neurophysiological effect beyond MEP amplitude modulation - though important limitations of this review (and conclusion) are discussed. This work raises questions concerning the mechanistic foundations and general efficacy of this device - the implications of which extend to the steadily increasing tDCS psychological literature.

Pupil dilation reflects perceptual selection and predicts subsequent stability in perceptual rivalry

During sustained viewing of an ambiguous stimulus, an individuals perceptual experience will generally switch between the different possible alternatives rather than stay fixed on one interpretation (perceptual rivalry). Here, we measured pupil diameter while subjects viewed different ambiguous visual and auditory stimuli. For all stimuli tested, pupil diameter increased just before the reported perceptual switch and the relative amount of dilation before this switch was a significant predictor of the subsequent duration of perceptual stability. These results could not be explained by blink or eye-movement effects, the motor response or stimulus driven changes in retinal input. Because pupil dilation reflects levels of norepinephrine (NE) released from the locus coeruleus (LC), we interpret these results as suggestive that the LC–NE complex may play the same role in perceptual selection as in behavioral decision making.

Meditation alters perceptual rivalry in Tibetan Buddhist monks

Neuroscientific studies of the mind are likely to benefit from the insights and skills of Tibetan Buddhist monks who have practiced the historic tradition of meditative training over many years — a point made recently at a forum between a selection of Buddhist leaders and distinguished scientists. Perceptual rivalries, such as binocular rivalry and motion induced blindness, are being used to study the neural mechanisms underlying consciousness and attention, as they involve fluctuations in conscious awareness despite unchanging external stimulation. Tapping into the ability of Tibetan Buddhist monks to control the flow of items being attended to and accessing consciousness, we found that meditation alters the inherent fluctuations in conscious state associated with perceptual rivalry.

A common oscillator for perceptual rivalries

Perceptual rivalry is an oscillation of conscious experience that takes place despite univarying, if ambiguous, sensory input. Much current interest is focused on the controversy over the neural site of binocular rivalry, a variety of perceptual rivalry for which a number of different cortical regions have been implicated. Debate continues over the relative role of higher levels of processing compared with primary visual cortex and the suggestion that different forms of rivalry involve different cortical areas. Here we show that the temporal pattern of disappearance and reappearance in motion-induced blindness (MIB) (Bonneh et al, 2001 Nature 411 798–801) is highly correlated with the pattern of oscillation reported during binocular rivalry in the same individual. This correlation holds over a wide range of inter-individual variation. Temporal similarity in the two phenomena was strikingly confirmed by the effects of the hallucinogen LSD, which produced the same, extraordinary, pattern of increased rhythmicity in both kinds of perceptual oscillation. Furthermore, MIB demonstrates the two properties previously considered characteristic of binocular rivalry. Namely the distribution of dominance periods can be approximated by a gamma distribution and, in line with Levelts second proposition of binocular rivalry, predominance of one perceptual phase can be increased through a reduction in the predominance time of the opposing phase. We conclude that (i) MIB is a form of perceptual rivalry, and (ii) there may be a common oscillator responsible for timing aspects of all forms of perceptual rivalry.

Transcranial direct current stimulation: five important issues we aren't discussing (but probably should be)

Transcranial Direct Current Stimulation (tDCS) is a neuromodulatory device often publicized for its ability to enhance cognitive and behavioral performance. These enhancement claims, however, are predicated upon electrophysiological evidence and descriptions which are far from conclusive. In fact, a review of the literature reveals a number of important experimental and technical issues inherent with this device that are simply not being discussed in any meaningful manner. In this paper, we will consider five of these topics. The first, inter-subject variability, explores the extensive between- and within-group differences found within the tDCS literature and highlights the need to properly examine stimulatory response at the individual level. The second, intra-subject reliability, reviews the lack of data concerning tDCS response reliability over time and emphasizes the importance of this knowledge for appropriate stimulatory application. The third, sham stimulation and blinding, draws attention to the importance (yet relative lack) of proper control and blinding practices in the tDCS literature. The fourth, motor and cognitive interference, highlights the often overlooked body of research that suggests typical behaviors and cognitions undertaken during or following tDCS can impair or abolish the effects of stimulation. Finally, the fifth, electric current influences, underscores several largely ignored variables (such as hair thickness and electrode attachments methods) influential to tDCS electric current density and flow. Through this paper, we hope to increase awareness and start an ongoing dialog of these important issues which speak to the efficacy, reliability, and mechanistic foundations of tDCS.

Onset Rivalry: Brief Presentation Isolates an Early Independent Phase of Perceptual Competition

When the left and right eyes are simultaneously presented with different images, observers typically report exclusive awareness of only one image. This phenomenon is termed binocular rivalry, reflecting the fact that the dominant image alternates every few seconds in a cycle of perceptual competition that continues indefinitely. Despite the apparent continuity in perceptual switching, we now demonstrate that the initial “onset” period is fundamentally different to all subsequent rivalry epochs. Using brief intermittent presentations, rivalry dominance shows strong biases such that the same target is perceived with each successive stimulus onset. These biases remain consistent within any given location, but vary across the visual field in a distribution that is stable over multiple weeks but highly idiosyncratic across observers. If the presentation exceeds ∼1sec at any location, however, the very different and much more balanced alternations of sustained binocular rivalry become apparent. These powerful onset biases are observed with brief intermittent presentations at a single location or with continual smooth motion of the targets. Periods of adaptation to one of the rivaling targets induced local switches in dominance to the non-adapted target. However, these effects were generally limited to the spatial site of adaptation and had less influence over each subsequent cycle of the target. We conclude that onset rivalry is independent of sustained rivalry and cannot be explained by local regions of monocular dominance or memory of past perceptual history, but rather reflects low-level, spatially localized factors that are stable over periods of weeks. These findings suggest that brief presentation paradigms are inappropriate for their current use in studies of the mechanisms underlying sustained rivalry. However, brief presentations are ideal for investigating early stages of perceptual competition.

Using Psilocybin to Investigate the Relationship between Attention, Working Memory, and the Serotonin 1A and 2A Receptors

Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin. Eight healthy human volunteers were tested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 Ag/kg), ketanserin (50 mg), and psilocybin and ketanserin. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggesting a primary involvement of the 5-HT1A receptor in the observed deficit. Based on physiological and pharmacological data, we speculate that this impaired attentional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity. The clinical relevance of these results is also discussed.

Effects of psilocybin on time perception and temporal control of behaviour in humans

Hallucinogenic psilocybin is known to alter the subjective experience of time. However, there is no study that systematically investigated objective measures of time perception under psilocybin. Therefore, we studied dose-dependent effects of the serotonin (5-HT)2A/1A receptor agonist psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine) on temporal processing, employing tasks of temporal reproduction, sensorimotor synchronization and tapping tempo. To control for cognitive and subjective changes, we assessed spatial working memory and conscious experience. Twelve healthy human volunteers were tested under placebo, medium (115μg/kg), and high (250μg/kg) dose conditions, in a double-blind experimental design. Psilocybin was found to significantly impair subjects’ ability to (1) reproduce interval durations longer than 2.5 sec, (2) to synchronize to inter-beat intervals longer than 2 sec and (3) caused subjects to be slower in their preferred tapping rate. These objective effects on timing performance were accompanied by working-memory deficits and subjective changes in conscious state, namely increased reports of ‘depersonalization’ and ‘derealization’ phenomena including disturbances in subjective ‘time sense.’ Our study is the first to systematically assess the impact of psilocybin on timing performance on standardized measures of temporal processing. Results indicate that the serotonin system is selectively involved in duration processing of intervals longer than 2 to 3 seconds and in the voluntary control of the speed of movement. We speculate that psilocybin’s selective disruption of longer intervals is likely to be a product of interactions with cognitive dimensions of temporal processing -presumably via 5-HT2A receptor stimulation.

Pupil Dilation Betrays the Timing of Decisions

The notion of “mind-reading” by carefully observing another individuals physiological responses has recently become commonplace in popular culture, particularly in the context of brain imaging. The question remains, however, whether outwardly accessible physiological signals indeed betray a decision before a person voluntarily reports it. In one experiment we asked observers to push a button at any time during a 10-s period (“immediate overt response”). In a series of three additional experiments observers were asked to select one number from five sequentially presented digits but concealed their decision until the trials end (“covert choice”). In these experiments observers either had to choose the digit themselves under conditions of reward and no reward, or were instructed which digit to select via an external cue provided at the time of the digit presentation. In all cases pupil dilation alone predicted the choice (timing of button response or chosen digit, respectively). Consideration of the average pupil-dilation responses, across all experiments, showed that this prediction of timing was distinct from a general arousal or reward-anticipation response. Furthermore, the pupil dilation appeared to reflect the post-decisional consolidation of the selected outcome rather than the pre-decisional cognitive appraisal component of the decision. Given the tight link between pupil dilation and norepinephrine levels during constant illumination, our results have implications beyond the tantalizing mind-reading speculations. These findings suggest that similar noradrenergic mechanisms may underlie the consolidation of both overt and covert decisions.