Non-invasive brain stimulation (NIBS) is a method for the study of cognitive function that is quickly gaining popularity. It bypasses the correlative approaches of other imaging techniques, making it ...possible to establish a causal relationship between cognitive processes and the functioning of specific brain areas. Like lesion studies, NIBS can provide information about where a particular process occurs. However, NIBS offers the opportunity to study brain mechanisms beyond process localisation, providing information about when activity in a given brain region is involved in a cognitive process, and even how it is involved. When using NIBS to explore cognitive processes, it is important to understand not only how NIBS functions but also the functioning of the neural structures themselves. We know that NIBS techniques have the potential to transiently influence behaviour by altering neuronal activity, which may have facilitatory or inhibitory behavioural effects, and these alterations can be used to understand how the brain works. Given that NIBS necessarily involves the relatively indiscriminate activation of large numbers of neurons, its impact on a neural system can be easily understood as modulation of neural activity that changes the relation between noise and signal. In this review, we describe the mutual interactions between NIBS and brain activity and provide an updated and precise perspective on the theoretical frameworks of NIBS and their impact on cognitive neuroscience. By transitioning our discussion from one aspect (NIBS) to the other (cognition), we aim to provide insights to guide future research.
If a conditioned stimulus or response has been inconsistently ("partially") reinforced, conditioned responding will take longer to extinguish than if responding had been established by consistent ...("continuous") reinforcement. This partial reinforcement extinction effect (PREE) is one of the best-known phenomena in associative learning but defies ready explanation by associative models which assume that a partial reinforcement schedule will produce weaker conditioning that should be less resistant to extinction. The most popular explanation of the PREE is that, during partial reinforcement, animals learn that recent nonreinforced (N) trials are associated with subsequent reinforcement (R), and therefore the presence of N trials during extinction serves to promote generalization of conditioning to extinction. According to sequential theory (Capaldi, 1966), animals can encode whole sequences (runs) of N trials and associate their memory of the sequence with subsequent R. The length of these N sequences during conditioning affects how long the animal will continue to respond during extinction. The present experiment used Pavlovian magazine approach conditioning with rats to test two predictions of this theory. Consistent with sequential theory, the PREE was sensitive to the length of the N sequence: conditioning with long sequences (runs of 3-5 N trials) produced a stronger PREE than conditioning with short sequences (runs of 1 or 2) even when the total number of N and R trials was held constant. Surprisingly, there was no PREE among rats trained with the short sequences. Moreover, contrary to the theory's prediction, interrupting the long N sequences with reinforced trials of a different conditioned stimulus did not affect the subsequent PREE. I conclude that uncertainty about reinforcement, rather than the memory of N sequences per se, is a key factor in the development of the PREE.
The Learning Curve, Revisited Harris, Justin A.
Journal of experimental psychology. Animal learning and cognition,
10/2022, Volume:
48, Issue:
4
Journal Article
Peer reviewed
The nature of the operations that support learning should be evident in the form or shape of the learning curve. For example, models that describe learning as an iterative error-correction process ...expect that the amount learned on each trial follows a decelerating (negatively inflected) function. That prediction is broadly consistent with the shape of the acquisition and extinction curves derived from mean measures of response strength. However, such evidence can be flawed because group means may not accurately portray the response curves of individual subjects in a conditioning experiment. Moreover, such evidence relies on strong assumptions about the way that what has been learned is expressed in responding. The current work presents a new analytical approach to reveal the rate of change in responding across the course of conditioning in individual animals. When applied to the conditioning and extinction data from a large sample of rats, this analysis confirms that responses are acquired and extinguish gradually and, in both cases, follow a decelerating learning curve. That is, changes in responding are largest at the start of conditioning or extinction and get progressively smaller as responding approaches an asymptote. However, rather than conforming to the specific shape predicted by an error-correction process, the results suggest that the amount learned increases according to a logarithmic function such that responding during conditioning and extinction is proportional to the log of the number of trials. The implications of these findings for models of associative learning are discussed.
The Importance of Trials Harris, Justin A.
Journal of experimental psychology. Animal learning and cognition,
10/2019, Volume:
45, Issue:
4
Journal Article
Peer reviewed
Open access
Many theories of conditioning describe learning as a process by which stored information about the relationship between a conditioned stimulus (CS) and unconditioned stimulus (US) is progressively ...updated upon each occasion (trial) that the CS occurs with, or without, the US. These simple trial-based descriptions can provide a powerful and efficient means of extracting information about the correlation between 2 events, but they fail to explain how animals learn about the timing of events. This failure has motivated models of conditioning in which animals learn continuously, either by explicitly representing temporal intervals between events or by sequentially updating an array of associations between temporally distributed elements of the CS and US. Here, I review evidence that some aspects of conditioning are not the consequence of a continuous learning process but reflect a trial-based process. In particular, the way that animals learn about the absence of a predicted US during extinction suggests that they encode and remember trials as single complete episodes rather than as a continuous experience of unfulfilled expectation of the US. These memories allow the animal to recognize repeated instances of nonreinforcement and encode these as a sequence that, in the case of a partial reinforcement schedule, can become associated with the US. The animal is thus able to remember details about the pattern of a CS's reinforcement history, information that affects how long the animal continues to respond to the CS when all reinforcement ceases.
The partial reinforcement extinction effect (PREE) refers to the phenomenon that conditioned responding extinguishes more slowly if subjects had been inconsistently ("partially") reinforced than if ...they had been reinforced on every trial ("continuously" reinforced). One largely successful account of the PREE, known as sequential theory (Capaldi, 1966), suggests that, when subjects are partially reinforced, they learn that memories of sequences of nonreinforced trials are associated with subsequent reinforcement. This association helps to maintain responding (i.e., delay extinction) when the subjects experience nonreinforced trials during extinction. Sequential theory's explanation of the PREE hinges on subjects learning sequences of nonreinforced trials during acquisition. However, direct evidence for such sequential learning is not available in previous studies of the PREE where animals are trained with multiple sequences of different lengths that are randomly intermixed and, therefore, cannot anticipate whether a given trial will be reinforced during acquisition. The current study conducted two experiments that trained rats with a single fixed trial sequence to provide evidence of sequential learning during conditioning, and then observe its effect on the PREE. Under one condition the rats did learn about the fixed sequence but did not subsequently show a PREE, whereas other rats that did show a PREE had not learned the trial sequences during conditioning. Therefore, contrary to sequential theory's prediction, our result suggests that learning about the trial sequence is neither necessary nor sufficient for the PREE. We suggest that the PREE may instead depend on uncertainty about whether the conditioned stimulus will be reinforced.
We have recently shown that the efficiency in stopping a response, measured using the stop signal task, is related to GABA
-mediated short-interval intracortical inhibition (SICI) in the primary ...motor cortex. In this study, we conducted two experiments on humans to determine whether training participants in the stop signal task within one session (Experiment 1) and across multiple sessions (Experiment 2) would increase SICI strength. For each experiment, we obtained premeasures and postmeasures of stopping efficiency and resting-state SICI, that is, during relaxed muscle activity (Experiment 1,
= 45, 15 male participants) and SICI during the stop signal task (Experiment 2,
= 44, 21 male participants). In the middle blocks of Experiment 1 and the middle sessions of Experiment 2, participants in the experimental group completed stop signal task training, whereas control participants completed a similar task without the requirement to stop a response. After training, the experimental group showed increased resting-state SICI strength (Experiment 1) and increased SICI strength during the stop signal task (Experiment 2). Although there were no overall behavioral improvements in stopping efficiency, improvements at an individual level were correlated with increases in SICI strength at rest (Experiment 1) and during successful stopping (Experiment 2). These results provide evidence of neuroplasticity in resting-state and task-related GABA
-mediated SICI in the primary motor cortex after response inhibition training. These results also suggest that SICI and stopping efficiency are temporally linked, such that a change in SICI between time points is correlated with a change in stopping efficiency between time points.
Background: Phthalates are compounds that are used in a wide range of consumer products. However, the contribution of dietary intake to phthalate exposure has not been well defined. Objective: The ...objective of this study was to assess the contribution of different food types to phthalate exposure. Phthalates are chemicals of concern because of the high levels measured in people and the environment, as well as the demonstrated toxicity in animal studies and limited epidemiological studies. Previous research, although limited, has suggested that phthalates contaminate food in various countries. Methods: We conducted an exploratory analysis of data collected as part of the 2003–2004 National Health and Nutrition Examination Survey (NHANES). Associations between dietary intake (assessed by a 24-hr dietary recall) for a range of food types (meat, poultry, fish, fruit, vegetable, and dairy) and phthalate metabolites measured in urine were analyzed using multiple linear regression modeling. Results: We found that metabolites of di-(2-ethylhexyl) phthalate (DEHP) and high-molecular-weight phthalate metabolites were associated with the consumption of poultry. Monoethyl phthalate, the metabolite of diethyl phthalate (DEP), was associated with vegetable consumption, specifically tomato and potato consumption. Discussion: These results, combined with results from previous studies, suggest that diet is an important route of intake for phthalates. Further research is needed to determine the sources of food contamination with these toxic chemicals and to describe the levels of contamination of U.S. food in a large, representative U.S. sample.
Valproic acid (VPA) is an anti-epileptic medication that increases the risk of neural tube defect (NTD) outcomes in infants exposed during gestation. Previous studies into VPA's mechanism of action ...have focused on alterations in gene expression and metabolism but have failed to consider how exposure changes the abundance of critical developmental proteins over time. This study evaluates the effects of VPA on protein abundance in the developmentally distinct tissues of the mouse visceral yolk sac (VYS) and embryo proper (EMB) using mouse whole embryo culture. Embryos were exposed to 600 μM VPA at 2 h intervals over 10 h during early organogenesis with the aim of identifying protein pathways relevant to VPA's mechanism of action in failed NTC. Protein abundance was measured through tandem mass tag (TMT) labeling followed by liquid chromatography and mass spectrometry. Overall, there were over 1500 proteins with altered abundance after VPA exposure in the EMB or VYS with 428 of these proteins showing previous gene expression associations with VPA exposure. Limited overlap of significant proteins between tissues supported the conclusion of independent roles for the VYS and EMB in response to VPA. Pathway analysis of proteins with increased or decreased abundance identified multiple pathways with mechanistic relevance to NTC and embryonic development including convergent extension, Wnt Signaling/planar cell polarity, cellular migration, cellular proliferation, cell death, and cytoskeletal organization processes as targets of VPA. Clustering of co-regulated proteins to identify shared patterns of protein abundance over time highlighted 4 h and 6/10 h as periods of divergent protein abundance between control and VPA-treated samples in the VYS and EMB, respectively. Overall, this study demonstrated that VPA temporally alters protein content in critical developmental pathways in the VYS and the EMB during early organogenesis in mice.
•Early organogenesis stage mouse conceptuses were treated with 600 μM VPA using whole embryo culture for 2–10 h.•Protein abundance was measured with tandem mass tags which identified 1510 proteins with differential abundance in the treated EMB or VYS.•Protein abundance changes were dynamic across time and based on tissue (embryo vs. visceral yolk sac).•428 of the significant proteins have previous associations with VPA exposure in mice based on the Comparative Toxicogenomics Database.•Pathway results relevant to neural tube closure included convergent extension, Wnt Signaling, and cytoskeletal organization.
Omega-3 polyunsaturated fatty acids (n-3 PUFA), enriched in fish oils, are increasingly recognized to have potential benefits for treating many human afflictions. Despite the importance of PUFA, ...their molecular mechanism of action remains unclear. One emerging hypothesis is that phospholipids containing n-3 PUFA acyl chains modify the structure and composition of membrane rafts, thus affecting cell signaling. In this study the two major n-3 PUFA found in fish oils, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, are compared. Using solid-state 2H NMR spectroscopy we explored the molecular organization of 1-2H31palmitoyl-2-eicosapentaenoylphosphatidylcholine (PEPC-d31) and 1-2H31palmitoyl-2-docosahexaenoylphosphatidylcholine (PDPC-d31) in mixtures with sphingomyelin (SM) and cholesterol (chol). Our results indicate that whereas both PEPC-d31 and PDPC-d31 can accumulate into SM-rich/chol-rich raftlike domains, the tendency for DHA to incorporate into rafts is more than twice as great as for EPA. We propose that DHA may be the more bioactive component of fish oil that serves to disrupt lipid raft domain organization. This mechanism represents an evolution in the view of how PUFA remodel membrane architecture.
Gold-standard psychological treatments such as exposure therapy are significantly undermined by high relapse rates. Although exposure-based treatments are capable of extinguishing maladaptive ...behaviours, these behaviours often spontaneously re-emerge over time – a phenomenon known in experimental research as spontaneous recovery. Understanding the factors that underlie this process is essential to improving long-term treatment outcomes. One factor that is yet to be properly examined is the effect of the total span of time across which behaviours are learned. To date, only one study by Gallistel & Papachristos (2020) has explored this in mice. Their findings suggest that long spans of acquisition learning result in greater spontaneous recovery compared to short spans. We investigated the effect of conditioning span across 5 experiments using rats. Contrary to Gallistel & Papachristos, our results found no difference in recovery between rats conditioned over a long span versus a short span, following short, intermediate and long delay intervals. This suggests that the span of conditioning does not affect the magnitude of recovery, nor the rate at which recovery emerges. Unexpectedly, conditioning span did appear to influence the strength of responding during acquisition, such that longer conditioning spans led to higher levels of responding. This finding could indicate that the learning process operates over a long time period beyond the original training episode. However, further research is needed to establish whether conditioning span influences the strength of what is learned, or instead the performance of a conditioned response.
•Conditioned responses can spontaneously recover after extinction, a phenomenon likened to relapse after exposure therapy.•Our study pursued recent evidence that the timespan across which behaviours are learned can affect spontaneous recovery.•We found that conditioning span did not affect the size of recovery or how quickly responding re-emerged after extinction.•Span did affect the amount of responding acquired, suggesting the learning process extends beyond the conditioning session.
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