The trial-spacing effect in olfactory patterning discriminations in honeybees

Harnessed bees conditioned to associate odors and sucrose reward learn to discriminate between olfactory mixtures and their odor components in negative (NP: A+, B+, AB-) and positive (PP: A-, B-, AB+) patterning experiments. They thus extend the proboscis to the reinforced (CS+) but not to the non-reinforced (CS-) stimuli. Using the same protocol, we studied whether or not trials, which are spaced in time, are more effective in supporting patterning discrimination than massed trials which succeed fast to each other ('trial-spacing effect'). Training followed a NP (4 A+, 4 B+, 8 AB-) or a PP (4 A-, 4 B-, 8 AB+) schedule, with a 1:1 ratio between CS+ and CS- trials (8 CS+ and 8 CS- trials). ITIs of 1, 3, 5 and 8min were used in both tasks. Increasing ITI resulted in better differentiation between reinforced and non-reinforced CSs in both NP and PP tasks. However, whereas only the longest ITI of 8min allowed discrimination in NP, PP could already be solved with an ITI of 5min. This difference might be due to the fact that NP, but not PP, would require the formation of a unique cue and thus longer processing times. We thus show that the trial-spacing effect, previously demonstrated for single stimulus conditioning, also determines performance in patterning tasks in which three different stimuli (A, B, AB) alternate so that elements have to be discriminated from their compound.     

Environmental enrichment increases responding to contextual cues but decreases overall conditioned fear in the rat

This study aimed at investigating the effects of environmental enrichment on various aspects of contextual processing in adult female rats. In experiment 1, simple conditioning was studied using either a training procedure allowing overshadowing of the contextual cues by signalling footshock with a discrete tone or a training procedure allowing a reduction of this overshadowing by explicitly unpairing the footshock and the tone. In experiment 2, contextual discrimination and contextual occasion-setting were assessed. Rats were daily exposed to two different contexts. In one context, a footshock was delivered 30s after the offset of a tone, whereas in the other context the same tone was presented alone. Experiment 3 examined familiarization to a new context. Experiment 1 showed that environmental enrichment reduced the overshadowing of contextual cues by the tone and also reduced freezing to the more predictive cue according to the training procedure used. Experiment 2 showed that environmental enrichment increased the ability of rats to discriminate two contexts. Experiment 3 showed that enriched rats familiarized faster to a new context than standard rats. Taken together, these results suggest that environmental enrichment in adult rats enhances learning about contextual cues and reduces overall fear associated with aversive events.     

Sex differences in learning and inhibition in spontaneously hypertensive rats

Few studies have addressed potential differences in the nature of cognitive impairment observed in males and females with ADHD. In Experiment 1, we examined sex differences in conditioned inhibitory behaviour in spontaneously hypertensive rats (SHR strain), a purported animal model of ADHD. Rats were presented with two types of trials during each of the 15 conditioning sessions. On some trials an auditory stimulus (a tone) was presented and followed immediately by delivery of food reward. On the remaining trials the tone was preceded by presentation of a visual stimulus and on those trials food was not delivered after the tone was presented. As training progressed, conditioned responding during presentation of the tone increased on reinforced trials and decreased during the non-reinforced trials, indicative of successful discrimination and inhibition. Overall, female SHR rats exhibited less conditioned overall food cup behaviour compared to male rats. Female SHR rats also required more training sessions until they responded significantly more during presentation of the tone on reinforced trials versus non-reinforced trials. In addition, the magnitude of the discrimination was smaller in female SHR rats compared to males. In contrast, no sex differences were observed in WKY rats (commonly-used control strain) in Experiment 2. Importantly, there were no significant sex differences in baseline activity or motivation during either experiment, indicating that performance differences could not account for the observed results. These results suggest that male and female SHR rats differ in their ability to form conditioned associations and inhibit behavioural responses and may provide a useful model for sex differences in cognitive dysfunction specific to ADHD.     

Hippocampal aspiration lesions fail to impair performance of a delayed alternation GO/NO-GO task.

Rats with hippocampal aspiration lesions (HIPP), cortical control lesions (CORT) or sham operations (SHAM) were trained on a delayed alternation GO/NO-GO task, in which responding was reinforced on odd-numbered GO trials but was not reinforced on even-numbered NO-GO trials. The number of responses required to obtain reinforcement, and the length of the inter-trial intervals (ITIs), were varied in different stages of the experiment. These systematic parametric manipulations were conducted in order to compare the roles of intra- and inter-trial information and the temporal spans which could be bridged in performing the task across the three different lesion groups. In addition, at a later stage of testing interference was introduced during the ITI to investigate its effect on task performance. The differences observed between the HIPP, CORT and SHAM groups were generally non-specific for trial type, with HIPP animals responding more overall on both NO-GO and, to a lesser extent, GO trials following each of the ITIs used. The results were consistent with the behavioural inhibition theory of hippocampal function, but not with the temporal discontiguity or working memory models. These surprising findings contrast sharply with those observed following an electrolytic lesion of the hippocampus, which has been reported to produce a delay-dependent impairment of performance on the GO/NO-GO task in rats using a very similar procedure. It is speculated that differences in performance following aspiration and electrolytic lesions may be at least partially attributable to rats adopting different response strategies induced by ITI differences in the two tasks. However, the results also raise an important question concerning the assumed equivalence of aspiration and electrolytic lesions of the hippocampus. The possibility that an interaction between procedural and lesion differences may contribute to the discrepant findings is also considered. The findings illustrate the sensitivity of the hippocampal mnemonic effect on what has become an established testing procedure in the hippocampal literature.     

Hippocampal lesions enhance configural learning by reducing proactive interference

Rats were trained on an operant conditional discrimination in which an ambiguous stimulus (X) indicated both the occasions on which responding in the presence of a second cue (A) would be reinforced and the occasions on which responding in the presence of a third cue (B) would not be reinforced (X → A+, A−, X → B−, B+). Both rats with neurotoxic lesions of the hippocampus and control rats learned this discrimination more rapidly when the training trials were widely spaced (mean intertrial interval of 8 min) than when they were massed (mean intertrial interval of 1 min). With spaced practice, lesioned and control rats learned this discrimination equally well. But when the training trials were massed, lesioned rats learned more rapidly than controls. At the end of training, performance of all rats was tested at three different intertrial intervals, 0.5 min, 1 min, and 8 min. The control rats trained with 8-min intertrial intervals showed deficits in discrimination performance when the test intertrial interval was 0.5 min or 1 min. An analysis of sequential effects indicated that a major source of this performance deficit was the control rats' failure to withhold responding on nonreinforced trials when those trials were immediately preceded by reinforced trials within 0.5 min or 1 min. In contrast, performance of lesioned rats was not affected by either the test intertrial interval or by the nature of preceding trials. Thus, with short intertrial intervals, hippocampal lesions may have improved learning or performance on a given trial by reducing proactive interference from the previous trial. Hippocampus 1998;8:138–146. © 1998 Wiley-Liss, Inc.     

Selective responsiveness of medial prefrontal cortex neurons to the meaningful stimulus with a low probability of occurrence in rats

Multi-unit neuronal activity was recorded in the medial prefrontal cortex (mPFC) of 13 chronically prepared male rats while they performed a two-tone discrimination task. Tones at 1000 and 2000 Hz were sequentially presented at intervals of 3-6 s. The duration of each tone was 0.8 s. Rats were trained to press a bar within 1.2 s after the cessation of the 1000 Hz tone (target), and not to press the bar when the other tone (non-target) was presented. Intracranial electrical stimulation (ICS) of the medial forebrain bundle was given as a reward immediately after the rats had correctly responded to the target tone. Probability of the target occurrence was either 30% or 70% in different sessions. When the target tone was presented on only 30% of the trials, the mPFC neurons in the majority of rats tested (10/13) exhibited phasic excitation about 100 ms after the onset of the target tone. However, when the target tone occurred on 70% of the trials, mPFC neurons in most of rats (11/13) did not show excitatory responses, and in some of them (5/13) were inhibited. No mPFC neurons exhibited significant responses to the non-target tone, regardless of its probability. These results suggest that the mPFC neurons selectively respond to meaningful events with a low probability of occurrence.     

Neural signatures of lexical tone reading

Research on how lexical tone is neuroanatomically represented in the human brain is central to our understanding of cortical regions subserving language. Past studies have exclusively focused on tone perception of the spoken language, and little is known as to the lexical tone processing in reading visual words and its associated brain mechanisms. In this study, we performed two experiments to identify neural substrates in Chinese tone reading. First, we used a tone judgment paradigm to investigate tone processing of visually presented Chinese characters. We found that, relative to baseline, tone perception of printed Chinese characters were mediated by strong brain activation in bilateral frontal regions, left inferior parietal lobule, left posterior middle/medial temporal gyrus, left inferior temporal region, bilateral visual systems, and cerebellum. Surprisingly, no activation was found in superior temporal regions, brain sites well known for speech tone processing. In activation likelihood estimation (ALE) meta‐analysis to combine results of relevant published studies, we attempted to elucidate whether the left temporal cortex activities identified in Experiment one is consistent with those found in previous studies of auditory lexical tone perception. ALE results showed that only the left superior temporal gyrus and putamen were critical in auditory lexical tone processing. These findings suggest that activation in the superior temporal cortex associated with lexical tone perception is modality‐dependent. Hum Brain Mapp, 36:304–312, 2015. © 2014 Wiley Periodicals, Inc .     

Temporal dynamics of the flash‐induced bouncing effect

Two identical visual disks moving toward each other on a two‐dimensional (2D) display are more likely to be perceived as “streaming through” than “bouncing off” each other after their coincidence. However, either a brief auditory tone or visual flash presented at the coincident moment of the disks can strikingly increase the incidence of the bouncing percept. Despite the neural substrates underlying the sound‐induced bouncing effect have been widely investigated, little is known about the neural mechanisms underlying the flash‐induced bouncing effect. The present study used event‐related potential recordings to explore the temporal dynamics of the flash‐induced bouncing effect. The results showed that the amplitude of the postcoincidence parietooccipital P2 component (190–230 ms after coincidence) elicited by the visual motion was significantly smaller on bouncing relative to streaming trials only when the flash was presented but not when absent. In addition, the parietal P3 component (330–430 ms) was found to be larger on bouncing than streaming trials when the flash was presented, but the opposite was true when no flash was presented. These electrophysiological findings suggest that the flash‐induced bouncing effect may occur at both perceptual and postperceptual stages of processing.     

Temporal context discrimination in patients with schizophrenia: associations with auditory hallucinations and negative symptoms

BACKGROUND: A deficit in remembering the temporal context of events (a type of source memory) has been observed in schizophrenia, and suggested to be associated with positive symptoms. METHODS: In order to investigate memory for temporal context, we administered a list discrimination task to a sample of schizophrenia patients and a sample of healthy controls. Participants were required to learn two lists of mixed high- and low-frequency words separated by 10 min, then to remember whether each word had been presented in the first or in the second list. RESULTS: The number of misattributions to the wrong list was significantly higher in patients than in healthy controls. However, the group difference was eliminated when recall efficiency was covaried. The number of list misattributions was higher in patients with auditory hallucinations than in the other patients, independently of verbal recall efficiency. By contrast, affective flattening and anhedonia were associated with fewer list misattributions of the high-frequency words. CONCLUSIONS: It is suggested that auditory hallucinations are associated with deficit in processing or remembering the temporal context. Conversely, certain negative symptoms are associated with reduced temporal context errors. The possible neural mechanisms involved in temporal context deficit as well as in these specific clinical symptoms are discussed.     

The effects of ethanol on diverse components of choice in the rat: reward discrimination,preference and relative valuation

Alcohol consumption impairs judgment and choice. How alcohol alters these crucial processes is primarily unknown. Choice can be fractionated into different components including reward discrimination, preference and relative valuation that can function together or in isolation depending upon diverse factors including choice context. We examined the diverse components and contextual effects by analyzing the effects of alcohol drinking on choice behavior in a task with a reduced level of temporal and spatial constraints. Rats were trained to drink 10% ethanol during 6 weeks of behavior testing using a combined sucrose‐fade and two‐bottle free‐choice procedure. Two different sucrose pellet outcomes (e.g., constant vs. variable) were presented each week to examine the impact of voluntary drinking on reward‐based decision‐making. Behavioral contexts of single option, free choice and extinction were examined for each outcome set. Comparisons were made between alcohol and control groups and within the alcohol group over time to inspect choice profiles. Between‐group results showed alcohol drinking animals expressed altered place preference and modified sucrose reward approach latencies. The within‐group profile showed that alcohol drinking animals can express adequate reward discrimination, preference and incentive contrast during free choice. All of these components were significantly reduced during the context of extinction. Control animals were also impacted by extinction but not as severely. The findings point to a need for a greater focus on the context and the diverse components of choice when examining external and internal factors influencing decision‐making during alcohol or other substance of abuse exposure.     

Hippocampal‐striatal functional connectivity supports processing of temporal expectations from associative memory

The hippocampus and dorsal striatum are both associated with temporal processing, but they are thought to play distinct roles. The hippocampus has been reported to contribute to storing temporal structure of events in memory, whereas the striatum contributes to temporal motor preparation and reward anticipation. Here, we asked whether the striatum cooperates with the hippocampus in processing the temporal context of memorized visual associations. In our task, participants were trained to implicitly form temporal expectations for one of two possible time intervals associated to specific cue‐target associations, and subsequently were scanned using ultra‐high‐field 7T functional magnetic resonance imaging. During scanning, learned temporal expectations could be violated when the pairs were presented at either the associated or not‐associated time intervals. When temporal expectations were met during testing trials, activity in left and right hippocampal subfields and right putamen decreased, compared to when temporal expectations were not met. Further, psycho‐physiological interactions showed that functional connectivity between left hippocampal subfields and caudate decreased when temporal expectations were not met. Our results indicate that the hippocampus and striatum cooperate to process implicit temporal expectation from mnemonic associations. Our findings provide further support for a hippocampal‐striatal network in temporal associative processing.     

Effects of short-lasting inactivations of the ventral hippocampus and medial septum on long-term and short-term acquisition of spatial information in rats

This study was aimed at testing the effects of a reversible inactivation of the hippocampal formation on long-term and short-term acquisition of spatial information. Rats chronically equipped with either bilateral cannulae into the ventral hippocampus or a single cannula into the medial septum had to locate, in a circular platform with 18 holes on the periphery, the unique hole leading to a hidden shelter in order to avoid bright light. In Expt. 1, following 16 days of training (1 trial/day, 24 h ITI) without physical intervention, the location of the correct hole was changed on both Days 17 and 23, and the rats were either sham-injected or injected with lidocaine. Both hippocampally and septally lidocaine-injected rats relearned the new location at a rate similar to corresponding sham-injected animals. In Expt. 2, a massed-trial version of the task was used, in which the rats had to learn a new hole location on each daily session (3 trials, ITI = 1 min). Animals were sham-injected or lidocaine-injected on alternate sessions. While sham-injected rats improved in orientational accuracy over successive trials, both hippocampally and septally lidocaine-injected rats failed to display any between-trial improvement. The impairment displayed by lidocaine-injected rats when their hippocampus was inactivated confirms the role of the hippocampus in short-term spatial memory (Expt. 2). In contrast, short-lasting inactivation of the hippocampus did not prevent long-term spatial learning (Expt. 1). These results suggest that the hippocampus could process information 'off-line' in the delay between temporally discontiguous learning trials, and show that short-term and long-term spatial learning rely on distinct neurobiological mechanisms.     

Dorsolateral prefrontal cortex lesions and discrimination of movement-produced cues by rhesus monkeys

Rhesus monkeys were trained on a conditional discrimination in which sequences of either 32 or 64 lever presses served as discriminative stimuli. For half the subjects, reinforcement was contingent upon choice of a red response key following a sequence of 32 presses (FR 32), and a white key after FR 64, with the position of the two key colors randomized across trials. The remaining subjects were reinforced for left key presses after FR 64, and right key presses after FR 32, with key color again randomized across trials. Ablation of dorsolateral prefrontal cortex resulted in postoperative deficits in all subjects, although 6 of 8 eventually remastered the task. This recovery was investigated in a second experiment, in which psychophysical functions were generated by varying the length of the shorter FR. Although dorsolateral lesions again produced a severe disruption in performance, the post-operative functions eventually obtained were identical to the preoperative functions. This pattern of marked impairment in retention of fixed ratio discriminations, but no change in asymptotic capacity, suggests participation of dorsolateral prefrontal cortex in processing kinesthetic information, possibly analogous to the role of inferior temporal cortex in processing visual information.     

Pharmacological evidence that both cognitive memory and habit formation contribute to within-session learning of concurrent visual discriminations

The monkey's ability to learn a set of visual discriminations presented concurrently just once a day on successive days (24-h ITI task) is based on habit formation, which is known to rely on a visuo-striatal circuit and to be independent of visuo-rhinal circuits that support one-trial memory. Consistent with this dissociation, we recently reported that performance on the 24-h ITI task is impaired by a striatal-function blocking agent, the dopaminergic antagonist haloperidol, and not by a rhinal-function blocking agent, the muscarinic cholinergic antagonist scopolamine. In the present study, monkeys were trained on a short-ITI form of concurrent visual discrimination learning, one in which a set of stimulus pairs is repeated not only across daily sessions but also several times within each session (in this case, at about 4-min ITIs). Asymptotic discrimination learning rates in the non-drug condition were reduced by half, from ∼11 trials/pair on the 24-h ITI task to ∼5 trials/pair on the 4-min ITI task, and this faster learning was impaired by systemic injections of either haloperidol or scopolamine. The results suggest that in the version of concurrent discrimination learning used here, the short ITIs within a session recruit both visuo-rhinal and visuo-striatal circuits, and that the final performance level is driven by both cognitive memory and habit formation working in concert.     

Entorhinal cortex lesions disrupt fear conditioning to background context but spare fear conditioning to a tone in the rat

Recent studies have shown that the integrity of the entorhinal cortex (EC) is not required for simple contextual conditioning. In background contextual conditioning, i.e., when a phasic cue is present during training, the involvement of the EC is still a matter of debate. Therefore, the present work further examines whether the EC is required for background contextual conditioning using a tone as the phasic cue. Rats sustaining either excitotoxic lesions of the EC or sham-lesions were trained with one of two procedures differing with respect to the predictive value of the tone: a paired procedure in which the tone perfectly predicts shock occurrence and overshadows context, and an unpaired procedure in which the predictive value of the tone is reduced. Conditioned fear was assessed by freezing responses during conditioning, reexposure to the training context, and reexposure to the tone in a new context. Postshock freezing was reduced in rats with entorhinal lesions. In all rats trained with the paired procedure, freezing to the context was low and freezing to the tone was high, suggesting that the tone has overshadowed the context during the conditioning session. The reverse pattern was observed with the unpaired procedure in sham-operated rats. In rats with entorhinal lesions trained with the unpaired procedure, freezing responses to the context was markedly reduced. In a new context, however, entorhinal-lesioned rats showed higher freezing scores than those of sham-lesioned rats. Freezing to the tone was unaffected by the lesion irrespective of the tone's predictive value. As a whole, these results support the notion that the EC is required for normal background contextual freezing.     

Cerebellar involvement in timing accuracy of rhythmic finger movements in essential tremor

The cerebellum is involved in the generation of essential tremor (ET) and cerebellar timing function is altered in patients with ET showing an increased variability of rhythmic hand movements. Using a sensor‐engineered glove, we evaluated motor behaviour during repetitive finger tapping movements in 15 patients with ET and in 11 age‐ and gender‐matched normal subjects. In addition, we investigated whether, in patients with ET, an inhibitory repetitive transcranial magnetic stimulation (1 Hz‐rTMS) over lateral cerebellum was able to change timing properties and motor behaviour. Patients with ET showed a longer touch duration (TD) and a lower inter tapping interval (ITI) than normal subjects. The temporal variability of the movement (coefficient of variation of ITI) was increased in patients with ET. Neither clinical rating scale or tremor measurements correlated with any parameter of motor performance in the ET group. 1 Hz‐rTMS over ipsilateral lateral cerebellum transiently affected the performance of patients with ET, by reducing TD values and normalizing ITI values. After 1 Hz‐rTMS, the coefficient of variation of ITI was restored to values similar to those of normal subjects. We postulate that the strategy to increase TD, probably adopted to allow a better perception of movement, can affect ITI and its variability. The results support the idea that the cerebellum plays a central role in the selection of motor strategy of rhythmic finger movements, particularly in terms of temporal organization of movement.     

Differential roles of the dorsal hippocampal regions in the acquisition of spatial and temporal aspects of episodic-like memory

Episodic memory refers to the recollection of what, where and when an event occurred. Computational models suggest that the dentate gyrus (DG) and the CA3 hippocampal subregions are involved in pattern separation and the rapid acquisition of episodes, while CA1 is involved in the formation of a temporal context. Most of the studies performed to test this hypothesis failed to simultaneously address the aspects of episodic memory. Recently, a new task of object recognition was validated in rats. In the first sample trial, the rat is exposed to four copies of an object. In second sample, the rat is exposed to four copies of a different object. In the test trial, two copies of each of the previous objects are presented. One copy of the object used in sample trial one is located in a different place, and it is expected to be the most explored. Our goal was to evaluate whether the pharmacological inactivation of the dorsal DG/CA3 and CA1 subregions could differentially impair the acquisition of the task. Inactivation of the DG/CA3 subregions impaired the spatial discrimination, while the temporal discrimination was preserved. Rats treated with muscimol in CA1 explored all the objects equally well, irrespective of place or presentation time. Our results are consistent with computational models that postulate a role for DG/CA3 in rapid encoding and in spatial pattern separation, and a role for CA1 in the in the formation of the temporal context of events and as well as in detecting spatial novelty.     

In the temporal organization of episodic memory,the hippocampus supports the experience of elapsed time

Space and time are both essential features of episodic memory, for which the hippocampus is critical (Howard & Eichenbaum, 2015). Spatial tasks have been used effectively to study the behavioral relevance of place cells. However, the behavioral paradigms utilized for the study of time cells have not used time duration as a variable that animals need to be aware of to solve the task. Therefore, the behavioral relevance of this cell firing is unclear. In order to directly study the role of the hippocampus in processing elapsed time, we created a novel time duration discrimination task. Rats learned to make a decision to turn left or right depending on the preceding tone duration (10 s, left turn; 20 s, right turn). Once the rats reached criterion performance of 90% correct on two out of three consecutive days, they received either an excitotoxic hippocampal lesion or a sham‐lesion surgery. After recovery, rats were tested to determine hippocampal involvement in discriminating time duration. Rats with hippocampal lesions performed at chance level on their first testing day postlesion, and they were impaired relative to the sham‐lesioned rats. Although the hippocampal‐lesioned rats began discriminating at above chance level, their performance never returned to criterion even with 50 days of postoperative testing. Furthermore, while sham rats showed no difference in the number of errors they made on 10‐ versus 20‐s delay trials, hippocampal lesion rats similarly improved their performance under the 10‐s delay condition, but not under the 20‐s delay condition. Results indicate that hippocampal lesions resulted in a selective impairment in discriminating elapsed time only during the longer delay trials. The implications of these results are discussed in relation to the limits of working‐memory capacity and to the role of sustained hippocampal time cell activity in memory performance depending on the perceived relevance of the delay period.     

Pre-surgical training ameliorates orbitofrontal-mediated impairments in spatial reversal learning

We recently reported that orbitofrontal cortical (OFC) lesions impaired reversal learning of an instrumental two-lever spatial discrimination task, a deficit manifested as increased perseveration on the pre-potent response. Here we examine whether exposure to reversal learning test pre-operatively may have a beneficial effect for future reversal learning of OFC-lesioned animals. Rats were trained on a novel instrumental two-lever spatial discrimination and reversal learning task, measuring both 'cognitive flexibility' and constituent processes including response inhibition. Both levers were presented, only one of which was reinforced. The rat was required to respond on the reinforced lever under a fixed ratio 3 schedule of reinforcement. Following attainment of criterion, two reversals were introduced. Rats were then matched according to their reversal performance and subjected to bilateral excitotoxic OFC lesions. Following recovery, a series of four reversals was presented. OFC lesions impaired neither retention nor reversal phases. These data, together with the previously reported reversal deficit following OFC lesions, suggest that OFC is not needed when task experience has been gained but it is necessary when task demands are relatively high.     

Auditory micropattern discrimination in brain damaged subjects

Patients with cerebral lesions were given two tests of pitch discrimination. The first was a pure tone discrimination test; in the second, complex tones were employed in which the pitch difference between the test tones was a consequence of the temporal microstructure of the stimuli. In contrast to non-fluent aphasics whose performance was normal for both tests, six of the seven patients having a fluent aphasia performed normally on the first test but revealed a significant deficit in the second. Patients with right temporal lesions also had the same pattern of deficit. The results suggest that the temporal lobes play a special role in the processing of auditory information in which the temporal structure of the stimuli is a critical feature.