David N. Harper

The effect of Parkinson’s disease on time estimation as a function of stimulus duration range and modality

The present research sought to investigate the role of the basal ganglia in timing of sub- and supra-second intervals via an examination of the ability of people with Parkinsons disease (PD) to make temporal judgments in two ranges, 100-500 ms, and 1-5 s. Eighteen non-demented medicated patients with PD were compared with 14 matched controls on a duration-bisection task in which participants were required to discriminate auditory and visual signal durations within each time range. Results showed that patients with PD exhibited more variable duration judgments across both signal modality and duration range than controls, although closer analyses confirmed a timing deficit in the longer duration range only. The findings presented here suggest the bisection procedure may be a useful tool in identifying timing impairments in PD and, more generally, reaffirm the hypothesised role of the basal ganglia in temporal perception at the level of the attentionally mediated internal clock as well as memory retrieval and/or decision-making processes.

Self-initiated versus externally cued reaction times in Parkinson's disease.

It has long been observed that patients with Parkinsons disease (PD) can sometimes react and move quickly in response to an external stimulus in a way that they cannot when required to initiate the movement themselves. This curious phenomenon has sometimes been called ‘paradoxical kinesis’. The present study was an attempt to demonstrate this phenomenon in patients with PD using an objective and quantifiable experimental procedure. A reaction time task was used in which participants had to press one of two computer keys, either left or right, to save a cartoon person on a computer screen from being run over by a motor car. In one condition, trials started after a traffic light appeared on the computer screen and then changed from red to green. In a second condition, the participants had to first press a third response key which resulted in the traffic light appearing on screen and changing from red to green. Participants also received both these conditions with the addition of a visual cue, an arrow, which told them in advance which direction to respond in (i.e., left or right key) on each trial. The purpose of the visual cue was to separate the effects of motor planning from motor activation. Healthy controls reacted quickest when they initiated trials themselves whereas the PD group were quicker to respond when trials were externally generated. Both groups were quicker under the visual cue condition. The results are discussed in terms of recent research which has suggested that two separate neural systems may be involved in externally generated or stereotyped actions and motor responses which require self-generated or nonroutine decision making.

The cage preferences of laboratory rats

Preference tests were used to assess a range of enrichment options for rats kept under standard New Zealand (and similar) caging conditions. The rats did not show significant preferences for most of the options, over an empty cage. The exceptions were shredded paper, a nesting box and a semi-enriched condition incorporating a range of modifications. These cage modifications are recommended for the enrichment of laboratory rats.

(+/-)3,4-methylenedioxymethamphetamine, d-amphetamine, and cocaine impair delayed matching-to-sample performance by an increase in susceptibility to proactive interference.

This study compared the effects of (+/-)3,4-methylenedioxymethamphetamine, d-amphetamine, and cocaine on performance of rats in a delayed matching-to-sample procedure using a variety of indices of performance to determine the mechanism by which working memory task impairments arise. All 3 drugs produced an overall delay-independent decrease in accuracy rather than a delay-dependent increase in the rate of forgetting. This impairment arose as a result of current-trial choice responses being progressively more affected by responses made in the immediately preceding trial as drug dose increased. Therefore, all 3 drugs produced qualitatively similar disruptions in memory task performance best characterized as an impairment arising from proactive sources of interference.

Differential effects of MDMA and scopolamine on working versus reference memory in the radial arm maze task

Previous research has suggested that the disruption to memory-task performance seen following acute exposure to 3,4-methylenedioxymethaphemtamine (MDMA) with rats might best be characterized as reference memory impairment rather than a working memory impairment. The current study specifically compared the effects of MDMA and scopolamine on measures of working versus reference memory in an eight-arm radial maze task. It was predicted that scopolamine would produce a greater impairment with respect to the working memory component of the task, whereas MDMA would produce a greater impairment to reference memory. On each trial rats were allowed to make a total of four arm visits in order to collect the reinforcers located at the end of different arms in the maze. Working memory errors were indicated by re-visiting an already visited arm during a trial, whereas visiting an arm that was never baited on any trial indicated a reference memory error. Using a within subjects design, rats were exposed to a range of doses of scopolamine and MDMA administered acutely. An interaction between drug type and memory error type was found. Specifically, scopolamine produced more working memory errors than reference memory errors, while MDMA produced the opposite pattern of significantly more reference memory errors compared to working memory error. This finding supported the hypothesis that MDMA disrupts reference memory processes in terms of an impairment in the strategies or rules used for solving memory tasks.

An Animal Model of Slot Machine Gambling: The Effect of Structural Characteristics on Response Latency and Persistence

Despite the prevalence of problem gamblers and the ethical issues involved in studying gambling behavior with humans, few animal models of gambling have been developed. When designing an animal model it is necessary to determine if behavior in the paradigm is similar to human gambling. In human studies, response latencies following winning trials and near win trials are greater than those following clear losses. Weatherly and Derenne (Anal Gambl Behav 1:79–89, 2007) investigated whether this pattern was found with rats working in an animal analogue of slot machine gambling. They found a similar pattern of response latencies but the subjects’ behavior did not come under control of the visual stimuli signalling the different outcomes. The animal model of slot machine gambling we used addressed procedural issues in Weatherly and Derenne’s model and examined whether reinforcer magnitude and the presence of near win trials influenced response latency and resistance to extinction. Response latencies of the six female Norway Hooded rats varied as a function of reinforcer magnitude and the presence of near-win trials. These results are consistent with prior research and with the idea that near win trials serve as conditional reinforcers.

Novel object recognition memory: measurement issues and effects of MDMA self-administration following short inter-trial intervals:

The present study was undertaken to examine effects of self-administered MDMA on novel object exploration (NOR) memory. Self-administration was conducted during daily 2 h tests that continued until a total of 165 mg/kg was self-administered (range = 13–41 days for individual rats). Control rats were placed in the self-administration boxes during daily sessions but did not receive any drug. One or 10 weeks following the last self-administration session, memory was assessed using a standard NOR task. When exploration time was used as the dependent measure for the control rats, there was no consistent pattern of change as a function of inter-trial interval (ITI) and exploration times failed to reveal decay in the function relating exploration to ITI. When number of approaches was examined as a function of ITI, however, there was a preference for the novel object following the short ITIs (1–15 min) and the function relating preference to ITI decayed with longer ITIs. When tested 7 days following the last self-administration session, rats that self-administered MDMA failed to demonstrate NOR even following the shortest ITI of 1 min. The data support the idea that MDMA self-administration produces cognitive deficits and are consistent with the idea that attentional processes become disrupted. There was, however, recovery of NOR memory when rats were tested following an extended drug-free period of 70 days. Thus, the deficits are transient and recovery was apparent.

Retroactive interference and rate of forgetting in delayed matching-to-sample performance

Previous evidence suggests that a disruptive stimulus presented during the delay interval of a delayed matching-to-sample trial increases the rate of forgetting by pigeons. However, disruptive events have generally been presented for a period of time proportional to the delay interval. Thus, the observed increase in forgetting may be the result of greater exposure to these events at longer delays than at shorter ones. This possibility was examined by comparing the effects of houselight illumination for the entire delay, half the delay, or a constant 1.5 sec of each delay on pigeons’ delayed matching-to-sample accuracy. Presenting the houselight for a period of time proportional to each delay (i.e., the entire delay or half the delay) impaired accuracy more at longer delays than at shorter delays. By contrast, when the houselight was illuminated for 1.5 sec, irrespective of delay length, there was a greater impairment in accuracy at shorter delays than at longer delays. Thus, the increased rate of forgetting previously reported in the literature may be the result of unequal application of a disrupting stimulus across delays.

Brain cells in the avian 'prefrontal cortex' code for features of slot-machine-like gambling.

Slot machines are the most common and addictive form of gambling. In the current study, we recorded from single neurons in the ‘prefrontal cortex’ of pigeons while they played a slot-machine-like task. We identified four categories of neurons that coded for different aspects of our slot-machine-like task. Reward-Proximity neurons showed a linear increase in activity as the opportunity for a reward drew near. I-Won neurons fired only when the fourth stimulus of a winning (four-of-a-kind) combination was displayed. I-Lost neurons changed their firing rate at the presentation of the first nonidentical stimulus, that is, when it was apparent that no reward was forthcoming. Finally, Near-Miss neurons also changed their activity the moment it was recognized that a reward was no longer available, but more importantly, the activity level was related to whether the trial contained one, two, or three identical stimuli prior to the display of the nonidentical stimulus. These findings not only add to recent neurophysiological research employing simulated gambling paradigms, but also add to research addressing the functional correspondence between the avian NCL and primate PFC.

Psychotropic placebos reduce the misinformation effect by increasing monitoring at test

A psychotropic placebo can help people resist the misinformation effect, an effect thought to be caused by a shift to more stringent source monitoring. When this shift occurs has been unclear. To address this issue we gave some people—but not others—a phoney cognitive-enhancing drug we called R273. Shortly afterwards, everyone took part in a misinformation effect experiment. To gather evidence about source monitoring we surreptitiously recorded time to read the misleading postevent narrative, and response time at test. Our findings suggest that people shifted to more stringent source monitoring at test. Moreover, people with higher working memory capacity (WMC) performed better than people with lower WMC—but only when they were told they had received R273, a finding that fits with research showing that WMC can confer advantages in situations demanding effortful control, but not when automatic heuristics suffice.