Inhibitory control hinders habit change.

Our habits constantly influence the environment, often in negative ways that amplify global environmental and health risks. Hence, change is urgent. To facilitate habit change, inhibiting unwanted behaviors appears to be a natural human reaction. Here, we use a novel experimental design to test how inhibitory control affects two key components of changing (rewiring) habit-like behaviors in healthy humans: the acquisition of new habit-like behavior and the simultaneous unlearning of an old one. We found that, while the new behavior was acquired, the old behavior persisted and coexisted with the new. Critically, inhibition hindered both overcoming the old behavior and establishing the new one. Our findings highlight that suppressing unwanted behaviors is not only ineffective but may even further strengthen them. Meanwhile, actively engaging in a preferred behavior appears indispensable for its successful acquisition. Our design could be used to uncover how new approaches affect the cognitive basis of changing habit-like behaviors.

Self-care tooling innovation in a disabled kea (Nestor notabilis).

Tooling is associated with complex cognitive abilities, occurring most regularly in large-brained mammals and birds. Among birds, self-care tooling is seemingly rare in the wild, despite several anecdotal reports of this behaviour in captive parrots. Here, we show that Bruce, a disabled parrot lacking his top mandible, deliberately uses pebbles to preen himself. Evidence for this behaviour comes from five lines of evidence: (i) in over 90% of instances where Bruce picked up a pebble, he then used it to preen; (ii) in 95% of instances where Bruce dropped a pebble, he retrieved this pebble, or replaced it, in order to resume preening; (iii) Bruce selected pebbles of a specific size for preening rather than randomly sampling available pebbles in his environment; (iv) no other kea in his environment used pebbles for preening; and (v) when other individuals did interact with stones, they used stones of different sizes to those Bruce preened with. Our study provides novel and empirical evidence for deliberate self-care tooling in a bird species where tooling is not a species-specific behaviour. It also supports claims that tooling can be innovated based on ecological necessity by species with sufficiently domain-general cognition.

Neurophysiological and functional neuroanatomical coding of statistical and deterministic rule information during sequence learning.

Humans are capable of acquiring multiple types of information presented in the same information stream. It has been suggested that at least two parallel learning processes are important during learning of sequential patterns-statistical learning and rule-based learning. Yet, the neurophysiological underpinnings of these parallel learning processes are not fully understood. To differentiate between the simultaneous mechanisms at the single trial level, we apply a temporal EEG signal decomposition approach together with sLORETA source localization method to delineate whether distinct statistical and rule-based learning codes can be distinguished in EEG data and can be related to distinct functional neuroanatomical structures. We demonstrate that concomitant but distinct aspects of information coded in the N2 time window play a role in these mechanisms: mismatch detection and response control underlie statistical learning and rule-based learning, respectively, albeit with different levels of time-sensitivity. Moreover, the effects of the two learning mechanisms in the different temporally decomposed clusters of neural activity also differed from each other in neural sources. Importantly, the right inferior frontal cortex (BA44) was specifically implicated in visuomotor statistical learning, confirming its role in the acquisition of transitional probabilities. In contrast, visuomotor rule-based learning was associated with the prefrontal gyrus (BA6). The results show how simultaneous learning mechanisms operate at the neurophysiological level and are orchestrated by distinct prefrontal cortical areas. The current findings deepen our understanding on the mechanisms of how humans are capable of learning multiple types of information from the same stimulus stream in a parallel fashion.

Implicit anticipation of probabilistic regularities: Larger CNV emerges for unpredictable events.

Anticipation of upcoming events plays a crucial role in automatic behaviors. It is, however, still unclear whether the event-related brain potential (ERP) markers of anticipation could track the implicit acquisition of probabilistic regularities that can be considered as building blocks of automatic behaviors. Therefore, in a four-choice reaction time (RT) task performed by young adults (N = 36), the contingent negative variation (CNV) as an ERP marker of anticipation was measured from the onset of a cue stimulus until the presentation of a target stimulus. Due to the probability structure of the task, target stimuli were either predictable or unpredictable, but this was unknown to participants. The cue did not contain predictive information on the upcoming target. Results showed that the CNV amplitude during response preparation was larger before the unpredictable than before the predictable target stimuli. In addition, although RTs increased, the P3 amplitude decreased for the unpredictable as compared with the predictable target stimuli, possibly due to the stronger response preparation that preceded stimulus presentation. These results suggest that enhanced attentional resources are allocated to the implicit anticipation and processing of unpredictable events. This might originate from the formation of internal models on the probabilistic regularities of the stimulus stream, which primarily facilitates the processing of predictable events. Overall, we provide ERP evidence that supports the role of implicit anticipation and predictive processes in the acquisition of probabilistic regularities.

Perceiving structure in unstructured stimuli: Implicitly acquired prior knowledge impacts the processing of unpredictable transitional probabilities.

It is unclear how implicit prior knowledge is involved and remains persistent in the extraction of the statistical structure underlying sensory input. Therefore, this study investigated whether the implicit knowledge of second-order transitional probabilities characterizing a stream of visual stimuli impacts the processing of unpredictable transitional probabilities embedded in a similar input stream. Young adults (N = 50) performed a four-choice reaction time (RT) task that consisted of structured and unstructured blocks. In the structured blocks, more probable and less probable short-range nonadjacent transitional probabilities were present. In the unstructured blocks, the unique combinations of the short-range transitional probabilities occurred with equal probability; therefore, they were unpredictable. All task blocks were visually identical at the surface level. While one-half of the participants completed the structured blocks first followed by the unstructured blocks, this was reversed in the other half of them. The change in the structure was not explicitly denoted, and no feedback was provided on the correctness of each response. Participants completing the structured blocks first showed faster RTs to more probable than to less probable short-range transitional probabilities in both the structured and unstructured blocks, indicating the persistent effect of prior knowledge. However, after extended exposure to the unstructured blocks, they updated this prior knowledge. Participants completing the unstructured blocks first showed the RT difference only in the structured blocks, which was not constrained by the preceding exposure to unpredictable stimuli. The results altogether suggest that implicitly acquired prior knowledge of predictable stimuli influences the processing of subsequent unpredictable stimuli. Updating this prior knowledge seems to require a longer stretch of time than its initial acquisition.

Frontal-midline theta frequency and probabilistic learning: A transcranial alternating current stimulation study.

Probabilistic learning is a fundamental cognitive ability that extracts and represents regularities of our environment enabling predictive processing during perception and acquisition of perceptual, motor, cognitive, and social skills. Previous studies show competition between neural networks related to executive function/working memory vs. probabilistic learning. Theta synchronization has been associated with the former while desynchronization with the latter in correlational studies. In the present paper our aim was to test causal relationship between fronto-parietal midline theta synchronization and probabilistic learning with non-invasive transcranial alternating current (tACS) stimulation. We hypothesize that theta synchronization disrupts probabilistic learning performance by modulating the competitive relationship. Twenty-six young adults performed the Alternating Serial Reaction Time (ASRT) task to assess probabilistic learning in two sessions that took place one week apart. Stimulation was applied in a double-blind cross-over within-subject design with an active theta tACS and a sham stimulation in a counter-balanced order between participants. Sinusoidal current was administered with 1 mA peak-to-peak intensity throughout the task (approximately 20 min) for the active stimulation and 30 s for the sham. We did not find an effect of fronto-parietal midline theta tACS on probabilistic learning comparing performance during active and sham stimulation. To influence probabilistic learning, we suggest applying higher current intensity and stimulation parameters more precisely aligned to endogenous brain activity for future studies.

Divided attention does not affect the acquisition and consolidation of transitional probabilities.

Statistical learning facilitates the efficient processing and prediction of environmental events and contributes to the acquisition of automatic behaviors. Whereas a minimal level of attention seems to be required for learning to occur, it is still unclear how acquisition and consolidation of statistical knowledge are affected when attention is divided during learning. To test the effect of divided attention on statistical learning and consolidation, ninety-six healthy young adults performed the Alternating Serial Reaction Time task in which they incidentally acquired second-order transitional probabilities. Half of the participants completed the task with a concurrent secondary intentional sequence learning task that was applied to the same stimulus stream. The other half of the participants performed the task without any attention manipulation. Performance was retested after a 12-h post-learning offline period. Half of each group slept during the delay, while the other half had normal daily activity, enabling us to test the effect of delay activity (sleep vs. wake) on the consolidation of statistical knowledge. Divided attention had no effect on statistical learning: The acquisition of second-order transitional probabilities was comparable with and without the secondary task. Consolidation was neither affected by divided attention: Statistical knowledge was similarly retained over the 12-h delay, irrespective of the delay activity. Our findings can contribute to a better understanding of the role of attentional processes in and the robustness of visuomotor statistical learning and consolidation.

Tracking the implicit acquisition of nonadjacent transitional probabilities by ERPs.

The implicit acquisition of complex probabilistic regularities has been found to be crucial in numerous automatized cognitive abilities, including language processing and associative learning. However, it has not been completely elucidated how the implicit extraction of second-order nonadjacent transitional probabilities is reflected by neurophysiological processes. Therefore, this study investigated the sensitivity of event-related brain potentials (ERPs) to these probabilistic regularities embedded in a sequence of visual stimuli without providing explicit information on the structure of the stimulus stream. Healthy young adults (N = 32) performed a four-choice RT task that included a sequential regularity between nonadjacent trials yielding a complex transitional probability structure. ERPs were measured relative to both stimulus and response onset. RTs indicated the rapid acquisition of the sequential regularity and the transitional probabilities. The acquisition process was also tracked by the stimulus-locked and response-locked P3 component: The P3 peak was larger for the sequence than for the random stimuli, while the late P3 was larger for less probable than for more probable short-range relations among the random stimuli. According to the RT and P3 effects, sensitivity to the sequential regularity is assumed to be supported by the initial sensitivity to the transitional probabilities. These results suggest that stimulus-response contingencies on the probabilistic regularities of the ongoing stimulus context are implicitly mapped and constantly revised. Overall, this study (1) highlights the role of predictive processes during implicit memory formation, and (2) delineates a potential to gain further insight into the dynamics of implicit acquisition processes.

Reduction of 2-methoxy-1,4-naphtoquinone by mitochondrially-localized Nqo1 yielding NAD+ supports substrate-level phosphorylation during respiratory inhibition.

Provision of NAD+ for oxidative decarboxylation of alpha-ketoglutarate to succinyl-CoA by the ketoglutarate dehydrogenase complex (KGDHC) is critical for maintained operation of succinyl-CoA ligase yielding high-energy phosphates, a process known as mitochondrial substrate-level phosphorylation (mSLP). We have shown previously that when NADH oxidation by complex I is inhibited by rotenone or anoxia, mitochondrial diaphorases yield NAD+, provided that suitable quinones are present (Kiss G et al., FASEB J 2014, 28:1682). This allows for KGDHC reaction to proceed and as an extension of this, mSLP. NAD(P)H quinone oxidoreductase 1 (NQO1) is an enzyme exhibiting diaphorase activity. Here, by using Nqo1-/- and WT littermate mice we show that in rotenone-treated, isolated liver mitochondria 2-methoxy-1,4-naphtoquinone (MNQ) is preferentially reduced by matrix Nqo1 yielding NAD+ to KGDHC, supporting mSLP. This process was sensitive to inhibition by specific diaphorase inhibitors. Reduction of idebenone and its analogues MRQ-20 and MRQ-56, menadione, mitoquinone and duroquinone were unaffected by genetic disruption of the Nqo1 gene. The results allow for the conclusions that i) MNQ is a Nqo1-preferred substrate, and ii) in the presence of suitable quinones, mitochondrially-localized diaphorases other than Nqo1 support NADH oxidation when complex I is inhibited. Our work confirms that complex I bypass can occur by quinones reduced by intramitochondrial diaphorases oxidizing NADH, ultimately supporting mSLP. Finally, it may help to elucidate structure-activity relationships of redox-active quinones with diaphorase enzymes.

ERPs differentiate the sensitivity to statistical probabilities and the learning of sequential structures during procedural learning.

Procedural learning facilitates the efficient processing of complex environmental stimuli and contributes to the acquisition of automatic behaviors. Although earlier findings suggest different temporal trajectories of the multiple learning processes within procedural learning, this has not been clarified at the level of neurocognitive correlates. Therefore, we investigated whether two prominent learning processes - statistical learning and sequence learning - can be distinguished using event-related brain potentials (ERPs) within the same experimental setting. Healthy young adults (N = 40) performed the Alternating Serial Reaction Time task while RTs and ERPs were measured time-locked to the onset of the task's stimuli. Both RT and N2 effects reflected the rapid acquisition of statistical probabilities. At the same time, these effects reflected the gradual learning of sequential structures. The amplitude change of the P3 reflected only gradual sequence learning. The P1 component was sensitive to both learning processes, which did not change as the task progressed. Our results altogether indicate that statistical learning and sequence learning develop differently at the level of both ERPs and overt responses. These findings could provide insight to the dynamic change of multiple parallel learning processes that occur during procedural memory formation.

Deconstructing Procedural Memory: Different Learning Trajectories and Consolidation of Sequence and Statistical Learning.

Procedural learning is a fundamental cognitive function that facilitates efficient processing of and automatic responses to complex environmental stimuli. Here, we examined training-dependent and off-line changes of two sub-processes of procedural learning: namely, sequence learning and statistical learning. Whereas sequence learning requires the acquisition of order-based relationships between the elements of a sequence, statistical learning is based on the acquisition of probabilistic associations between elements. Seventy-eight healthy young adults (58 females and 20 males) completed the modified version of the Alternating Serial Reaction Time task that was designed to measure Sequence and Statistical Learning simultaneously. After training, participants were randomly assigned to one of three conditions: active wakefulness, quiet rest, or daytime sleep. We examined off-line changes in Sequence and Statistical Learning as well as further improvements after extended practice. Performance in Sequence Learning increased during training, while Statistical Learning plateaued relatively rapidly. After the off-line period, both the acquired sequence and statistical knowledge was preserved, irrespective of the vigilance state (awake, quiet rest or sleep). Sequence Learning further improved during extended practice, while Statistical Learning did not. Moreover, within the sleep group, cortical oscillations and sleep spindle parameters showed differential associations with Sequence and Statistical Learning. Our findings can contribute to a deeper understanding of the dynamic changes of multiple parallel learning and consolidation processes that occur during procedural memory formation.

Catabolism of GABA, succinic semialdehyde or gamma-hydroxybutyrate through the GABA shunt impair mitochondrial substrate-level phosphorylation.

GABA is catabolized in the mitochondrial matrix through the GABA shunt, encompassing transamination to succinic semialdehyde followed by oxidation to succinate by the concerted actions of GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH), respectively. Gamma-hydroxybutyrate (GHB) is a neurotransmitter and a psychoactive drug that could enter the citric acid cycle through transhydrogenation with α-ketoglutarate to succinic semialdehyde and d-hydroxyglutarate, a reaction catalyzed by hydroxyacid-oxoacid transhydrogenase (HOT). Here, we tested the hypothesis that the elevation in matrix succinate concentration caused by exogenous addition of GABA, succinic semialdehyde or GHB shifts the equilibrium of the reversible reaction catalyzed by succinate-CoA ligase towards ATP (or GTP) hydrolysis, effectively negating substrate-level phosphorylation (SLP). Mitochondrial SLP was addressed by interrogating the directionality of the adenine nucleotide translocase during anoxia in isolated mouse brain and liver mitochondria. GABA eliminated SLP, and this was rescued by the GABA-T inhibitors vigabatrin and aminooxyacetic acid. Succinic semialdehyde was an extremely efficient substrate energizing mitochondria during normoxia but mimicked GABA in abolishing SLP in anoxia, in a manner refractory to vigabatrin and aminooxyacetic acid. GHB could moderately energize liver but not brain mitochondria consistent with the scarcity of HOT expression in the latter. In line with these results, GHB abolished SLP in liver but not brain mitochondria during anoxia and this was unaffected by either vigabatrin or aminooxyacetic acid. It is concluded that when mitochondria catabolize GABA or succinic semialdehyde or GHB through the GABA shunt, their ability to perform SLP is impaired.