Lateral habenula lesions impair the association of a conditioned stimulus with the absence of an unconditioned stimulus: Retardation task.

Recent studies have indicated that the lateral habenula (LHb) mediates the association of a conditioned stimulus (CS) with the absence of an unconditioned stimulus (US). We generated a CS-no US association using an explicit unpaired training procedure and evaluated the conditioned inhibitory properties using the modified version of the retardation-of-acquisition procedure, one of the procedures for assessing conditioned inhibition. First, rats in the unpaired group received explicit unpaired light (CS) and food (US) presentations, followed by light-food pairings. Rats in the comparison group received paired training alone. The rats in the two groups showed increased food-cup responses to light over paired training. However, rats in the unpaired group showed a slower acquisition of light and food excitatory conditioning than those in the comparison group. Light acquired conditioned inhibitory properties through explicitly unpaired training, as evidenced by its slowness. Second, we examined the effects of the LHb lesions on the decremental effects of unpaired learning on subsequent excitatory learning. Sham-operated rats exhibited decremental effects of unpaired learning on subsequent excitatory learning, while rats with LHb neurotoxic lesions did not. Third, we tested whether preexposure to the same number of lights presented in the unpaired training retarded the acquisition of subsequent excitatory conditioning. Preexposure to light did not significantly retard the acquisition of subsequent excitatory associations, with no LHb lesion effects. These findings indicate that LHb is critically involved in the association between CS and the absence of US.

Age-related impairments on the touchscreen paired associates learning (PAL) task in male rats.

Discovery research in rodent models of cognitive aging is instrumental for identifying mechanisms of behavioral decline in old age that can be therapeutically targeted. Clinically relevant behavioral paradigms, however, have not been widely employed in aged rats. The current study aimed to bridge this translational gap by testing cognition in a cross-species touchscreen-based platform known as paired-associates learning (PAL) and then utilizing a trial-by-trial behavioral analysis approach. This study found age-related deficits in PAL task acquisition in male rats. Furthermore, trial-by-trial analyses and testing rats on a novel interference version of PAL suggested that age-related impairments were not due to differences in vulnerability to an irrelevant distractor, motivation, or to forgetting. Rather, impairment appeared to arise from vulnerability to accumulating, proactive interference, with aged animals performing worse than younger rats in later trial blocks within a single testing session. The detailed behavioral analysis employed in this study provides new insights into the etiology of age-associated cognitive deficits.

Altered motor cortical plasticity in patients with hepatic encephalopathy: A paired associative stimulation study.

OBJECTIVE: Hepatic encephalopathy (HE) is a potentially reversible brain dysfunction caused by liver failure. Altered synaptic plasticity is supposed to play a major role in the pathophysiology of HE. Here, we used paired associative stimulation with an inter-stimulus interval of 25 ms (PAS25), a transcranial magnetic stimulation (TMS) protocol, to test synaptic plasticity of the motor cortex in patients with manifest HE. METHODS: 23 HE-patients and 23 healthy controls were enrolled in the study. Motor evoked potential (MEP) amplitudes were assessed as measure for cortical excitability. Time courses of MEP amplitude changes after the PAS25 intervention were compared between both groups. RESULTS: MEP-amplitudes increased after PAS25 in the control group, indicating PAS25-induced synaptic plasticity in healthy controls, as expected. In contrast, MEP-amplitudes within the HE group did not change and were lower than in the control group, indicating no induction of plasticity. CONCLUSIONS: Our study revealed reduced synaptic plasticity of the primary motor cortex in HE. SIGNIFICANCE: Reduced synaptic plasticity in HE provides a link between pathological changes on the molecular level and early clinical symptoms of the disease. This decrease may be caused by disturbances in the glutamatergic neurotransmission due to the known hyperammonemia in HE patients.

Plastic responsiveness of motor cortex to paired associative stimulation depends on cerebellar input.

OBJECTIVE: The extent of plastic responses of motor cortex (M1) to paired associative stimulation (PAS) varies among healthy subjects. Continuous theta-burst stimulation (cTBS) of cerebellum enhances the mean PAS-induced plasticity in groups of healthy subjects. We tested whether the initial status of Responder or Non -Responder to PAS, influenced the effect of cerebellar stimulation on PAS-induced plasticity. METHODS: We assessed in 19 young healthy volunteers (8 Responders, 11 Non-Responders to PAS), how cTBS and iTBS (intermittent TBS) applied to the cerebellum before a PAS protocol influenced the plastic responsiveness of M1 to PAS. We tested whether the PAS-induced plastic effects could be depotentiated by a short cTBS protocol applied to M1 shortly after PAS and whether cerebellar stimulation influenced GABA-ergic intracortical inhibition and M1 plasticity in parallel. RESULTS: Cerebellar cTBS restored the M1 response to PAS in Non-Responders while cerebellar iTBS turned the potentiating response to PAS to a depressive response in both groups. The depotentiation protocol abolished both responses. CONCLUSION: Non-Responder status to PAS is a state of M1 amenable to bidirectional plastic modulation when primed by a change in cerebello-thalamic drive. SIGNIFICANCE: The meaning of lack of responsiveness to certain protocols probing plasticity should be reconsidered.

Age affects procedural paired-associates learning in the grey mouse lemur (Microcebus murinus).

The ability to associate memorized objects with their location in space gradually declines during normal aging and can drastically be affected by neurodegenerative diseases. This study investigates object-location paired-associates learning (PAL) in the grey mouse lemur (Microcebus murinus), a nonhuman primate model of brain aging. Touchscreen-based testing of 6 young adults (1-5 years) and 6 old adults (> 7 years) in the procedural rodent dPAL-task revealed significant age-related performance decline, evident in group differences in the percentage of correct decision during learning and the number of sessions needed to reach a predefined criterion. Response pattern analyses suggest decreased susceptibility to relative stimulus-position biases in young animals, facilitating PAL. Additional data from a subset of "overtrained" individuals (n = 7) and challenge sessions using a modified protocol (sPAL) further suggest that learning criteria routinely used in animal studies on PAL can underestimate the endpoint at which a stable performance is reached and that more conservative criteria are needed to improve construct validity of the task. To conclude, this is the first report of an age effect on dPAL and corroborates the role of mouse lemurs as valuable natural nonhuman primate models in aging research.

Evidence for preferential attachment: Words that are more well connected in semantic networks are better at acquiring new links in paired-associate learning.

Here, we view the mental lexicon as a semantic network where words are connected if they are semantically related. Steyvers and Tenenbaum (Cognitive Science, 29, 41-78, 2005) proposed that the growth of semantic networks follows preferential attachment, the observation that new nodes are more likely to connect to preexisting nodes that are more well connected (i.e., the rich get richer). If this is the case, well-connected known words should be better at acquiring new links than poorly connected words. We tested this prediction in three paired-associate learning (PAL) experiments in which participants memorized arbitrary cue-response word pairs. We manipulated the semantic connectivity of the cue words, indexed by the words' free associative degree centrality. Experiment 1 is a reanalysis of the PAL data from Qiu and Johns (Psychonomic Bulletin & Review, 27, 114-121, 2020), in which young adults remembered 40 cue-response word pairs (e.g., nature-chain) and completed a cued recall task. Experiment 2 is a preregistered replication of Qiu and Johns. Experiment 3 addressed some limitations in Qiu and Johns's design by using pseudowords as the response items (e.g., boot-arruity). The three experiments converged to show that cue words of higher degree centrality facilitated the recall/recognition of the response items, providing support for the notion that better-connected words have a greater ability to acquire new links (i.e., the rich do get richer). Importantly, while degree centrality consistently accounted for significant portions of variance in PAL accuracy, other psycholinguistic variables (e.g., concreteness, contextual diversity) did not, suggesting that degree centrality is a distinct variable that affects the ease of verbal associative learning.

Multi-domain cognitive assessment of male mice shows space radiation is not harmful to high-level cognition and actually improves pattern separation.

Astronauts on interplanetary missions - such as to Mars - will be exposed to space radiation, a spectrum of highly-charged, fast-moving particles that includes 56Fe and 28Si. Earth-based preclinical studies show space radiation decreases rodent performance in low- and some high-level cognitive tasks. Given astronaut use of touchscreen platforms during training and space flight and given the ability of rodent touchscreen tasks to assess functional integrity of brain circuits and multiple cognitive domains in a non-aversive way, here we exposed 6-month-old C57BL/6J male mice to whole-body space radiation and subsequently assessed them on a touchscreen battery. Relative to Sham treatment, 56Fe irradiation did not overtly change performance on tasks of visual discrimination, reversal learning, rule-based, or object-spatial paired associates learning, suggesting preserved functional integrity of supporting brain circuits. Surprisingly, 56Fe irradiation improved performance on a dentate gyrus-reliant pattern separation task; irradiated mice learned faster and were more accurate than controls. Improved pattern separation performance did not appear to be touchscreen-, radiation particle-, or neurogenesis-dependent, as 56Fe and 28Si irradiation led to faster context discrimination in a non-touchscreen task and 56Fe decreased new dentate gyrus neurons relative to Sham. These data urge revisitation of the broadly-held view that space radiation is detrimental to cognition.

Paired-associate learning, animacy, and imageability effects in the survival advantage.

The current study examined animacy and paired-associate learning through a survival-processing paradigm (Nairne et al. in Journal of Experimental Psychology: Learning, Memory, and Cognition, 33(2), 263-273, 2007; Schwartz & Brothers, 2014). English-speaking monolingual participants were asked to learn a set of new word translations to improve their chances of survival or to improve their study abroad experience. Animate and inanimate words were included in this task, to further examine animacy effects in cued recall paradigms (Popp & Serra in Journal of Experimental Psychology: Learning, Memory, and Cognition, 42(2), 186-201, 2016; VanArsdall et al. in Experimental Psychology, 60(3), 172-178, 2013). Across sentence-completion, matching, and picture-naming tasks, learning was facilitated by the survival context, relative to the study abroad context and an intentional learning condition. Scenario ratings indicated this survival advantage could also be a function of higher imageability ratings for the survival context than for the study abroad context. Replicating previous findings with cued recall, inanimate words were overall better remembered than animate words, across all three tasks, though survival processing facilitated language-learning for both animate and inanimate categories. This 'reverse animacy effect' replicated previous findings by Popp and Serra (Journal of Experimental Psychology: Learning, Memory, and Cognition, 42(2), 186-201, 2016), showing animate words can interfere with a participant's ability to create associations with their words, including those in a new language. These results are discussed with regards to the widely-reliable survival and animacy advantages, with a particular emphasis on the role of imageability in this paradigm.

Learning correspondences between magnitudes, symbols and words: Evidence for a triple code model of arithmetic development.

According to the Triple Code Model, early arithmetic development depends on learning the mappings between non-verbal representations of magnitude (quantity) and symbolic verbal (number words) and visual (Arabic numerals) representations of number. We examined this hypothesis in a sample of 166 4- to 7-year old children. Children completed 4 paired-associate learning tasks and a broad range of measures assessing early numerical (symbolic and non-symbolic magnitude comparison, digit writing, arithmetic) and reading skills (letter-sound knowledge, phoneme awareness, rapid automatized naming, word reading). A path model showed that paired-associate learning tasks involving mapping magnitudes onto verbal or visual stimuli predicted arithmetic performance over and above other well-established predictors. This relationship was specific to arithmetic and, consistent with the Triple Code Model, highlights that mapping between non-symbolic magnitude representations and the corresponding symbolic forms (verbal and visual) is important to the development of arithmetic skills.

Adolescent exposure to Δ9-tetrahydrocannabinol delays acquisition of paired-associates learning in adulthood.

RATIONALE AND OBJECTIVES: Adolescence is a sensitive period of brain development, during which there may be a heightened vulnerability to the effects of drug use. Despite this, the long-term effects of cannabis use during this developmental period on cognition are poorly understood. METHODS: We exposed adolescent rats to escalating doses of Δ9-tetrahydrocannabinol (THC)-the primary psychoactive component of cannabis-or vehicle solution during postnatal days (PND) 35-45, a period of development that is analogous to human adolescence (THC doses: PND 35-37, 2.5 mg/kg; PND 38-41, 5 mg/kg; PND 42-45, 10 mg/kg). After a period of abstinence, in adulthood, rats were tested on an automated touchscreen version of a paired-associates learning (PAL) task to assess their ability to learn and recall object-location associations. Prepulse inhibition (PPI) of the startle response was also measured at three time points (5 days, 4 months, and 6 months after exposure) to assess sensorimotor gating, the ability to filter out insignificant sensory information from the environment. RESULTS: Compared to rats exposed to vehicle alone, rats exposed to THC during adolescence took longer to learn the PAL task when tested in adulthood, even when trials contained visually identical stimuli that differed only in location. Despite this, no differences were observed later in testing, when trials contained visually distinct stimuli in different locations. Rats exposed to THC also displayed impairments in sensorimotor gating, as measured by prepulse inhibition of the startle response, though this deficit did appear to decrease over time. CONCLUSION: Taken together, THC exposure during adolescence produces long-term deficits in associative learning and sensorimotor gating, though the impact of these deficits seems to diminish with time. Thus, adolescence may represent a period of neurocognitive development that is vulnerable to the harms of cannabis use, though the stability of such harms is uncertain.

Paired associate learning deficits in poor readers: The contribution of phonological input and output processes.

It is well-established that poor readers exhibit deficits in paired associate learning (PAL), and there is increasing evidence for a phonological locus of these deficits. However, it remains unclear whether poor performance stems from difficulties specific to the phonological output system or difficulties that affect both phonological input and output processes. Understanding these deficits is important not only in the context of PAL but also for informing broader theories of typical and atypical reading development. We developed a novel paradigm that allowed us to assess PAL in the presence and absence of phonological output demands. In total, 14 poor readers and 14 age-matched controls were first trained to criterion in verbal-visual PAL before being tested in the visual-verbal direction. The results showed that poor readers learned at the same rate as controls in verbal-visual PAL, even when the nonword stimuli were phonologically confusable. Yet, despite having reached the same criterion as controls in verbal-visual PAL, poor readers exhibited robust impairments for those same paired associates in visual-verbal PAL. The overall pattern of results is most consistent with the conclusion that PAL deficits reflect impairments to the phonological output system; however, results that may challenge this interpretation are also discussed.

Moderate prenatal alcohol exposure impairs performance by adult male rats in an object-place paired-associate task.

Memory impairments, including spatial and object processing, are often observed in individuals with Fetal Alcohol Spectrum Disorders. The neurobiological basis of memory deficits after prenatal alcohol exposure (PAE) is often linked to structural and functional alterations in the medial temporal lobe, including the hippocampus. Recent evidence suggests that the medial temporal lobe plays a critical role in processing high-order sensory stimuli such as complex objects and their associated locations in space. In the first experiment, we tested male rat offspring with moderate PAE in a medial temporal-dependent object-place paired-associate (OPPA) task. The OPPA task requires a conditional discrimination between an identical pair of objects presented at two spatial locations 180° opposite arms of a radial arm maze. Food reinforcement is contingent upon selecting the correct object of the pair for a given spatial location. Adult rats were given a total of 10 trials per day over 14 consecutive days of training. PAE male rats made significantly more errors than male saccharin (SACC) control rats during acquisition of the OPPA task. In Experiment 2, rats performed an object-discrimination task in which a pair of objects were presented in a single arm of the maze. Moderate PAE and SACC control rats exhibited comparable performance. The results suggest that moderate PAE rats can learn to discriminate objects, but are impaired when required to discriminate between objects on the basis of spatial location in the environment.

Exploring factors underlying children's acquisition and retrieval of sound-symbol association skills.

Letter knowledge is considered an important cognitive foundation for learning to read. The underlying mechanisms of the association between letter knowledge and reading skills are, however, not fully understood. Acquiring letter knowledge depends on the ability to learn and retrieve sound-symbol pairings. In the current study, this process was explored by setting preschool children's (N = 242, mean age = 5.57 years) performance in the acquisition and retrieval of a paired associate learning (PAL) task in relation to their letter knowledge as well as to their performance in tasks assessing precursors of reading skills (i.e., phonological awareness, rapid automatized naming, phonological short-term memory, backward recall, and response inhibition). Multiple regression analyses revealed that performance in the acquisition of the PAL task was significantly associated with phonological awareness and backward recall, whereas performance in the retrieval of the PAL task was significantly associated with rapid automatized naming, phonological awareness, and backward recall. Moreover, PAL proved to be mediating the relation between reading precursors and letter knowledge. Together, these findings indicate that the acquisition of letter knowledge may depend on a visual-verbal associative learning mechanism and that different factors contribute to the acquisition and retrieval of such visual-verbal associations.

Postretrieval Relearning Strengthens Hippocampal Memories via Destabilization and Reconsolidation.

Memory reconsolidation is hypothesized to be a mechanism by which memories can be updated with new information. Such updating has previously been shown to weaken memory expression or change the nature of the memory. Here we demonstrate that retrieval-induced memory destabilization also allows that memory to be strengthened by additional learning. We show that for rodent contextual fear memories, this retrieval conditioning effect is observed only when conditioning occurs within a specific temporal window opened by retrieval. Moreover, it necessitates hippocampal protein degradation at the proteasome and engages hippocampal Zif268 protein expression, both of which are established mechanisms of memory destabilization-reconsolidation. We also demonstrate a conceptually analogous pattern of results in human visual paired-associate learning. Retrieval-relearning strengthens memory performance, again only when relearning occurs within the temporal window of memory reconsolidation. These findings link retrieval-mediated learning in humans to the reconsolidation literature, and have potential implications both for the understanding of endogenous memory gains and strategies to boost weakly learned memories.SIGNIFICANCE STATEMENT Memory reconsolidation allows existing memories to be updated with new information. Previous research has demonstrated that reconsolidation can be manipulated pharmacologically and behaviorally to impair problematic memories. In this article, we show that reconsolidation can also be exploited to strengthen memory. This is shown both in rats, in a fear memory setting, and in a human declarative memory setting. For both, the behavioral conditions necessary to observe the memory strengthening match those that are required to trigger memory reconsolidation. There are several behavioral approaches that have previously been shown convincingly to strengthen memory. The present demonstration that reconsolidation can underpin long-lasting memory improvements may both provide an underlying mechanism for such approaches and provide new strategies to boost memories.

Sentence Context and Word-Picture Cued-Recall Paired-Associate Learning Procedure Boosts Recall in Normal and Mild Alzheimer's Disease Patients.

INTRODUCTION: The aim of this study was to employ the word-picture paradigm to examine the effectiveness of combined pictorial illustrations and sentences as strong contextual cues. The experiment details the performance of word recall in healthy older adults (HOA) and mild Alzheimer's disease (AD). The researchers enhanced the words' recall with word-picture condition and when the pair was associated with a sentence contextualizing the two items. METHOD: The sample was composed of 18 HOA and 18 people with mild AD. Participants memorized 15 pairs of words under word-word and word-picture conditions, with and without a sentence context. In the paired-associate test, the first item of the pair was read aloud by participants and used to elicit retrieval of the associated item. RESULTS: The findings suggest that both HOA and mild-AD pictures improved item recall compared to word condition such as sentences which further enabled item recall. Additionally, the HOA group performs better than the mild-AD group in all conditions. CONCLUSIONS: Word-picture and sentence context strengthen the encoding in the explicit memory task, both in HOA and mild AD. These results open a potential window to improve the memory for verbalized instructions and restore sequential abilities in everyday life, such as brushing one's teeth, fastening one's pants, or drying one's hands.

Acute stress, but not corticosterone, facilitates acquisition of paired associates learning in rats using touchscreen-equipped operant conditioning chambers.

Acute stress influences learning and memory in humans and rodents, enhancing performance in some tasks while impairing it in others. Typically, subjects preferentially employ striatal-mediated stimulus-response strategies in spatial memory tasks following stress, making use of fewer hippocampal-based strategies which may be more cognitively demanding. Previous research demonstrated that the acquisition of rodent paired associates learning (PAL) relies primarily on the striatum, while task performance after extensive training is impaired by hippocampal disruption. Therefore, we sought to explore whether the acquisition of PAL, an operant conditioning task involving spatial stimuli, could be enhanced by acute stress. Male Long-Evans rats were trained to a predefined criterion in PAL and then subjected to either a single session of restraint stress (30 min) or injection of corticosterone (CORT; 3 mg/kg). Subsequent task performance was monitored for one week. We found that rats subjected to restraint stress, but not those rats injected with CORT, performed with higher accuracy and efficiency, when compared to untreated controls. These results suggest that while acute stress enhances the acquisition of PAL, CORT alone does not. This dissociation may be due to differences between these treatments and their ability to produce sufficient catecholamine release in the amygdala, a requirement for stress effects on memory.

Intrinsic spontaneous brain activity predicts individual variability in associative memory in older adults.

Older adults demonstrate notable individual differences in associative memory. Here, resting-state functional magnetic resonance imaging (rsfMRI) was used to investigate whether intrinsic brain activity at rest could predict individual differences in associative memory among cognitively healthy older adults. Regional amplitude of low-frequency fluctuations (ALFF) analysis and a correlation-based resting-state functional connectivity (RSFC) approach were used to analyze data acquired from 102 cognitively normal elderly who completed the paired-associative learning test (PALT) and underwent fMRI scans. Participants were divided into two groups based on the retrospective self-reports on whether or not they utilized encoding strategies during the PALT. The behavioral results revealed better associative memory performance in the participants who reported utilizing memory strategies compared with participants who reported not doing so. The fMRI results showed that higher associative memory performance was associated with greater functional connectivity between the right superior frontal gyrus and the right posterior cerebellum lobe in the strategy group. The regional ALFF values in the right superior frontal gyrus were linked to associative memory performance in the no-strategy group. These findings suggest that the regional spontaneous fluctuations and functional connectivity during rest may subserve the individual differences in the associative memory in older adults, and that this is modulated by self-initiated memory strategy use.

The sandwich priming paradigm does not reduce lexical competitor effects.

We investigated the mechanisms underlying sandwich priming, a procedure in which a brief preprime target presentation precedes the conventional mask-prime-target sequence, used to study orthographic similarity. Lupker and Davis (2009) showed the sandwich paradigm enhances orthographic priming effects: With primes moderately related to targets, sandwich priming produced significant facilitation, but conventional priming did not. They argued that unlike conventional priming, sandwich priming is not susceptible to an uncontrolled counteractive inhibitory process, lexical competition, that cancels out moderate facilitation effects. They suggest lexical competition is eliminated by preactivating the target's representation, privileging the target over similar lexical units (competitors). As such, it better measures orthographic relatedness between primes and targets, a key purpose of many priming studies. We tested whether elimination of lexical competition could indeed account for the observed orthographic priming boost with sandwich priming. In three lexical decision experiments and accompanying simulations with a competitive network model, we compared priming effects in three preprime procedures: no preprime (conventional), identity (target) preprime (sandwich), and competitor preprime (included to exacerbate lexical competition). The related prime conditions consisted of replaced-letters, shared neighbor (one-letter-different from both competitor preprime and target), and transposed-all-letter nonword primes. Contrary to the model's predictions, the competitor preprime did not attenuate (Experiment 1) or even reverse the priming effect (Experiment 2). Moreover, the competitor enabled facilitatory priming that was absent with no preprime (Experiment 3). These data suggested that the sandwich orthographic boost could not be attributed to reduced lexical competition but rather to prelexical processes in word recognition. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Modulation of human corticospinal excitability by paired associative stimulation in patients with amyotrophic lateral sclerosis and effects of Riluzole.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes an impairment in both the upper and lower motor neurons. The recent description of numerous non-motor signs points to an involvement of the neocortex networks that is more complex than was previously believed. Paired associative stimulation (PAS), a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation, can enhance motor output in the contralateral hand through an NMDA-mediated sensorimotor mechanism. OBJECTIVE: To describe the effects of PAS on ALS patients before and after Riluzole intake compared with healthy subjects. METHODS: PAS was used to detect differences between 24 newly-diagnosed ALS patients and 25 age-matched healthy controls. MEP amplitude from the abductor pollicis brevis was considered before PAS, immediately after (T0) and after 10 (T10), 20 (T20), 30 (T30) and 60 (T60) minutes. Statistical significance was calculated using RM-ANOVA. RESULTS: In healthy controls, PAS significantly increased MEP amplitude at T10, T20 and T30 (p < 0.05). In ALS patients, a significant increase in MEP amplitude was also observed after 60 min (p < 0.05), thus demonstrating NMDA-mediated enhanced facilitatory plasticity. After two weeks of riluzole intake, no MEP amplitude increase was evident after PAS at any time point. In three monomelic-onset ALS patients, a long lasting sensorimotor facilitation was evident only in the hemisphere corresponding to the affected side and appeared in the opposite hemisphere when the patients manifested contralateral symptoms. CONCLUSIONS: PAS may be considered a useful tool when investigating NMDA-mediated neocortical networks in ALS patients and the modulation of such networks after anti-glutamatergic drug intake.

Attention training to pleasant stimuli in anxiety.

Attentional bias for threatening stimuli in anxiety is a common finding in the literature. The present study addressed whether attention training toward pleasant stimuli can reduce anxiety symptoms and induce a processing bias in favor of pleasant information in nonpatients who were selected to score similarly to individuals with generalized anxiety or panic disorder on a measure of worry or physiological arousal, respectively. Participants were randomly assigned to attention training to pleasant (ATP) stimuli or to a placebo control (PC) condition. All participants completed baseline and post-test dot-probe measures of attentional bias while event-related brain potentials were recorded. As expected, worry symptoms decreased in the ATP and not PC condition. ATP was also associated with early evidence (P100 amplitude) of greater attentional prioritization of probes replacing neutral stimuli within threat-neutral word pairs from pre-to-post intervention and later RT evidence of facilitated processing of probes replacing pleasant stimuli within pleasant-threat word pairs at post compared to PC. PC was associated with later evidence (P300 latency) of less efficient evaluation of probes following pleasant stimuli within pleasant-threat word pairs from pre-to-post and later RT evidence of facilitated processing of probes following threat stimuli within pleasant-threat word pairs at post compared to ATP. Results highlight early and later mechanisms of attention processing changes and underscore the potential of pleasant stimuli in optimizing attention-training interventions for anxiety.