Subanaesthetic doses of ketamine reduce but do not eliminate predictive coding responses: implications for mechanisms of sensory disconnection.

BACKGROUND: Sensory disconnection is a key feature of sleep and anaesthesia. We have proposed that predictive coding offers a framework for understanding the mechanisms of disconnection. Low doses of ketamine that do not induce disconnection should thus diminish predictive coding, but not abolish it. METHODS: Ketamine was administered to 14 participants up to a blood concentration of 0.3 µg ml-1 Participants were played a series of tones comprising a roving oddball sequence while electroencephalography evoked response potentials were recorded. We fit a Bayesian observer model to the tone sequence, correlating neural activity with the prediction errors generated by the model using linear mixed effects models and cluster-based statistics. RESULTS: Ketamine modulated prediction errors associated with the transition of one tone to the next (transitional probability), but not how often tones changed (environmental volatility), of the system. Transitional probability was reduced when blood concentrations of ketamine were increased to 0.2-0.3 µg ml-1 (96-208 ms, P=0.003); however, correlates of prediction error were still evident in the electroencephalogram (124-168 ms, P=0.003). Prediction errors related to environmental volatility were associated with electroencephalographic activity before ketamine (224-284 ms, P=0.028) and during 0.2-0.3 µg ml-1 ketamine (108-248 ms, P=0.003). At this subanaesthetic dose, ketamine did not exert a dose-dependent modulation of prediction error. CONCLUSIONS: Subanaesthetic dosing of ketamine reduced correlates of predictive coding but did not eliminate them. Future studies should evaluate whether states of sensory disconnection, including anaesthetic doses of ketamine, are associated with a complete absence of predictive coding responses. CLINICAL TRIAL REGISTRATION: NCT03284307.

Filling your time: Auditory flutter alters perceived duration via stimulus-locked responses.

In the current article, we examined the flutter-duration illusion; the extension of perceived duration when an interval is filled with auditory flutter. Participants reproduced flutter-filled and empty durations while electrophysiological activity was recorded. As expected, participants over-produced durations when they were filled with auditory flutter rather than unfilled. Using multivariate pattern analysis, we found several differentiating patterns of neural activity while participants listened to either flutter-filled or empty intervals. However, in subsequent single trial analysis, only two of these clusters predicted perceived duration in the flutter condition; one occurring in line with the second click of the flutter, and one in line with the fourth click. We relate this finding to the N1P2 component and P3a component to timing initiation and arousal, respectively.

Anaesthetics and time perception: A review.

Consciousness requires subjective experience in the "now." Establishing "now," however, necessitates temporal processing. In the current article, we review one method of altering consciousness, anaesthetic drug administration, and its effects on perceived duration. We searched PubMed, PsycInfo, and ScienceDirect databases, and article reference sections, for combinations of anaesthetic drugs and time perception tasks, finding a total of 36 articles which met our inclusion criteria. We categorised these articles with regard to whether they altered the felt passage of time, short or long interval timing, or were motor timing tasks. We found that various drugs alter the perceived passage of time; ketamine makes time subjectively slow down while GABAergic drugs make time subjectively speed up. At a short interval there is little established evidence of a shift in time perception, though temporal estimates appear more variable. Similarly, when asked to use time to optimise responses (i.e., in motor timing tasks), various anaesthetic agents make timing more variable. Longer durations are estimated as lasting longer than their objective duration, though there is some variation across articles in this regard. We conclude by proposing further experiments to examine time perception under altered states of consciousness and ask whether it is possible to perceive the passage of time of events which do not necessarily reach the level of conscious perception. The variety of methods used raises the need for more systematic investigations of time perception under anaesthesia. We encourage future investigations into the overlap of consciousness and time perception to advance both fields.

Local context effects in the magnitude-duration illusion: Size but not numerical value sequentially alters perceived duration.

Many aspects of an event can change perceived duration. A common example of this is the magnitude-duration illusion, in which a high magnitude (e.g. large or high value) stimulus will be perceived to last longer than a low magnitude stimulus. The effects of magnitude on perceived duration are normally considered in terms of global context effects; what is large depends on the stimuli used throughout the experiment. In the current article, we examine local context effects in the magnitude-duration illusion, how trial-by-trial changes in magnitude affect the subjective duration of an event. We performed two experiments in which numerical magnitude and stimulus size were varied within either the example phase or reproduction phase of a temporal reproduction task. We showed that in the current trial the combined value-size magnitude presented in the example phase affected subsequent reproductions, while the magnitude presented in the reproduction phase did not. The size magnitude presented in the reproduction phase also affected the reproduction in the following trial, such that a larger stimulus in the current reproduction phase resulted in shorter reproductions in the next reproduction phase. This indicates that low level stimulus properties (i.e. size) can act to contextualize subsequent stimulus properties, which in turn affect perceived duration. The findings of our experiments add local, low-level, context effects to the known modifiers of perceived duration, as well as provide evidence with regards to the role of magnitude in interval timing.

Decisional carryover effects in interval timing: Evidence of a generalized response bias.

Decisional carryover refers to the tendency to report a current stimulus as being similar to a prior stimulus. In this article, we assess decisional carryover in the context of temporal judgments. Participants performed a temporal bisection task wherein a probe between a long and short reference duration (Experiment 1) was presented on every trial. In Experiment 2, every other trial presented a duration the same as the short or long reference duration. In Experiment 3, we concurrently varied both the size and duration of stimuli. Experiment 1 demonstrated the typical decisional carryover effect in which the current response was assimilated towards the prior response. In Experiment 2, this was not the case. Conversely, in Experiment 2, we demonstrated decisional carryover from the prior probe decision to the reference duration trials, a judgment which should have been relatively easy. In Experiment 3, we found carryover in the judgment of both size and duration, and a tendency towards decisional carryover having a larger effect size when participants were making size judgments. Together, our findings indicate that decisional carryover in duration judgments occur given relatively response-certain trials and that this effect appears to be similar in both size and duration judgments. This suggest that decisional carryover is indeed decisional in nature, rather than due to assimilative effects in perception, and that the difficulty of judging the previous test stimuli may play a role in whether assimilation occurs in the following trial when judging duration.

The expected oddball: effects of implicit and explicit positional expectation on duration perception.

The oddball duration effect describes how a rare stimulus amongst a string of standard stimuli is perceived to have a longer duration than the standards, even if they are of the same objective duration. Several theories have been proposed to explain this phenomenon. In order to adjudicate between opposing explanations, we have borrowed three extensively studied paradigms from the variable foreperiod literature: the sequential foreperiod, temporal cueing and a skewed foreperiod distribution. This approach allowed us to examine the effects of positional expectation on perceived oddball duration, while avoiding confounds from first-order positioning of the oddball in a sequence of standards. Through these three experiments, we demonstrate a clear role of positional expectation in the lengthening of the perceived duration of an oddball. We show that this expectation effect is separable from other drivers of the oddball duration illusion.

Time in the motor cortex: Motor evoked potentials track foreperiod duration without concurrent movement.

Transcranial magnetic stimulation (TMS) allows for the monitoring of motor cortex dynamics in preparation for response. Using this method, it has previously been shown that motor evoked potentials (MEPs) are suppressed as a response approaches. In the current article, we applied TMS while participants either relaxed or contracted their first dorsal interosseous muscle. We varied the time at which TMS was applied, however, unlike previous studies, no participant response was required. Using this method, we provide evidence that MEPs systematically decrease with the duration of the trial, while inhibition is not similarly affected. Further, we found some evidence that MEPs are inversely proportional to the duration of the prior trial. These findings have ramifications for other research interested in the application of TMS, especially when used across multiple possible points in a trial. Further, this finding shows a role for the motor cortex in timing more broadly.

Short-term effects on temporal judgement: Sequential drivers of interval bisection and reproduction.

Our prior experiences provide the background with which we judge subsequent events. In the time perception literature one common finding is that providing participants with a higher percentage of a particular interval can skew judgment; intervals will appear longer if the distribution of intervals contains more short experiences. However, changing the distribution of intervals that participants witness also changes the short-term, interval-to-interval, sequence that participants experience. In the experiment presented here, we kept the overall distribution of intervals constant while manipulating the immediately-prior experience of participants. In temporal bisection, this created a noted assimilation effect; participants judged intervals as shorter given an immediately preceding short interval. In interval reproduction, there was no effect of the immediately prior interval length unless the prior interval had a linked motor command. We thus proposed that the immediately prior interval provided a context by which a subsequent interval is judged. However, in the case of reproduction, where a subsequent interval is reproduced, rather than seen, the effects of contextualization are attenuated.

The Role of Transcranial Direct Current Stimulation (tDCS) in Tourette Syndrome: A Review and Preliminary Findings.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that is being investigated for a variety of neurological and psychiatric conditions. Preliminary evidence suggests that tDCS may be useful in the treatment of Tourette Syndrome (TS). This paper reviews the literature on the use of tDCS in commonly occurring comorbid conditions that are relevant to its proposed use in TS. We describe the protocol for a double-blind, crossover, sham-controlled trial of tDCS (Trial ID: ACTRN12615000592549, registered at www.anzctr.org.au) investigating the efficacy, feasibility, safety, and tolerability of tDCS in patients with TS aged 12 years and over. The intervention consists of cathodal tDCS positioned over the Supplementary Motor Area. Patients receive either sham tDCS for three weeks followed by six weeks of active tDCS (1.4 mA, 18 sessions over six weeks), or six weeks of active sessions followed by three weeks of sham sessions, with follow-up at three and six months. Pilot findings from two patients are presented. There was a reduction in the frequency and intensity of patients' tics and premonitory urges, as well as evidence of improvements in inhibitory function, over the course of treatment. Larger scale studies are indicated to ascertain the maintenance of symptom improvement over time, as well as the long-term consequences of the repetitions of sessions.