Impaired Encoding Research Articles

Moderate-intensity cardiovascular exercise performed before motor practice attenuates offline implicit motor learning in stroke survivors but not age-matched neurotypical adults.

The acute impact of cardiovascular exercise on implicit motor learning of stroke survivors is still unknown. We investigated the effects of cardiovascular exercise on implicit motor learning of mild-moderately impaired chronic stroke survivors and neurotypical adults. We addressed whether exercise priming effects are time-dependent (e.g., exercise before or after practice) in the encoding (acquisition) and recall (retention) phases. Forty-five stroke survivors and 45 age-matched neurotypical adults were randomized into three sub-groups: BEFORE (exercise, then motor practice), AFTER (motor practice, then exercise), and No-EX (motor practice alone). All sub-groups practiced a serial reaction time task (five repeated and two pseudorandom sequences per day) on three consecutive days, followed 7days later by a retention test (one repeated sequence). Exercise was performed on a stationary bike, (one 20-min bout per day) at 50% to 70% heart rate reserve. Implicit motor learning was measured as a difference score (repeated-pseudorandom sequence response time) during practice (acquisition) and recall (delayed retention). Separate analyses were performed on the stroke and neurotypical groups using linear mixed-effects models (participant ID was a random effect). There was no exercise-induced benefit on implicit motor learning for any sub-group. However, exercise performed before practice impaired encoding in neurotypical adults and attenuated retention performance of stroke survivors. There is no benefit to implicit motor learning of moderately intense cardiovascular exercise for stroke survivors or age-matched neurotypical adults, regardless of timing. Practice under a high arousal state and exercise-induced fatigue may have attenuated offline learning in stroke survivors.

Speech-Encoding Deficits in Neonates Born Large-for-Gestational Age as Revealed With the Envelope Frequency-Following Response.

The present envelope frequency-following response (FFR ENV ) study aimed at characterizing the neural encoding of the fundamental frequency of speech sounds in neonates born at the higher end of the birth weight continuum (>90th percentile), known as large-for-gestational age (LGA). Twenty-five LGA newborns were recruited from the maternity unit of Sant Joan de Déu Barcelona Children's Hospital and paired by age and sex with 25 babies born adequate-for-gestational age (AGA), all from healthy mothers and normal pregnancies. FFR ENV s were elicited to the/da/ syllable and recorded while the baby was sleeping in its cradle after a successful universal hearing screening. Neural encoding of the stimulus' envelope of the fundamental frequency (F 0ENV ) was characterized through the FFR ENV spectral amplitude. Relationships between electrophysiological parameters and maternal/neonatal variables that may condition neonatal neurodevelopment were assessed, including pregestational body mass index (BMI), maternal gestational weight gain and neonatal BMI. LGA newborns showed smaller spectral amplitudes at the F 0ENV compared to the AGA group. Significant negative correlations were found between neonatal BMI and the spectral amplitude at the F 0ENV . Our results indicate that in spite of having a healthy pregnancy, LGA neonates' central auditory system is impaired in encoding a fundamental aspect of the speech sounds, namely their fundamental frequency. The negative correlation between the neonates' BMI and FFR ENV indicates that this impaired encoding is independent of the pregnant woman BMI and weight gain during pregnancy, supporting the role of the neonatal BMI. We suggest that the higher adipose tissue observed in the LGA group may impair, via proinflammatory products, the fine-grained central auditory system microstructure required for the neural encoding of the fundamental frequency of speech sounds.

Decomposing Working Memory in Recurrent Major Depression: Impaired Encoding and Limited Maintenance Immune-to-Encoding Constraint.

It is generally believed that working memory (WM) is dysfunctional in depression. However, whether this impaired performance originates from impaired encoding, maintenance or both stages is still unclear. Here, we aimed to decompose the abnormal characteristics of encoding and maintenance in patients with recurrent major depressive disorder (MDD). Thirty patients and thirty-nine healthy controls completed a spatial working memory task where the encoding time and the retention time could vary under different load levels. Encoding performance was assessed by comparing accuracies between short and long encoding times, and maintenance performance was assessed by comparing accuracies between short and long retention times. The results show a lower performance in depression than the controls. However, while the decreased accuracy by long retention (vs. short retention) was increased by a short encoding time in the control group, the retention performance of the depression group did not further suffer from the short encoding time. The generally impaired encoding, together with limited maintenance of immunity against the constrained encoding time, suggests a common bias for fixed internal processing over external processing in recurrent MDD. The paradigm provided in this study can be a convenient and efficient clinical test for assessing the WM encoding and maintenance function.

Associative-memory deficit as a function of age and stimuli serial position.

Studies have shown associative-memory decline in aging. While the literature is inconclusive regarding the source of the deficit, some researchers argue that it is caused by impaired encoding and maintenance processes in working-memory (WM). Successful retrieval of a stimulus depends on its sequential presentation in the learning list: stimuli at the beginning or the end of the learning list benefit from higher retrieval probability. These effects are known as “primacy” and “recency” effects, respectively. In the case of the primacy-effect, stimuli at early list positions benefit from extensive rehearsal that results in enhanced consolidation and trace in long-term memory (LTM). In the case of the recency-effect, target stimuli at later serial positions are still maintained in WM and can therefore be effortlessly retrieved. Considering these effects could shed light on the involvement of WM in associative-binding. Both behavioral and neuroimaging researchers have studied associative-decline in aging. However, no work has explicitly tested age differences in memory for items versus associations as a function of stimuli serial position (SSP). In the current study, 22 younger and 22 older adults were recruited to participate in a study aimed to test the separate and joint effects of both SSP and aging on memory-recognition of items and associations. In the task used, retrieval was manipulated for SSP (beginning/middle/end of the list) and item/associations recognition modes. We hypothesized that greater associative-decline will be observed in older adults, specifically for recently presented material. The results showed that both groups presented a significant associative-deficit at the recency positions; this decrease was additive and did not correspond to the expected interaction effect. Further analysis showed that the source of associative-memory decline for stimuli at recency position in older adults resulted from an increase in false-alarm (FA) rates. These results support the involvement of WM-binding impairment in aging.

Differential roles of nucleus reuniens and perirhinal cortex in Pavlovian trace fear conditioning in rats.

The nucleus reuniens (RE) and the perirhinal cortex (PRC) are two major relay stations that interconnect the hippocampus (HPC) and the medial prefrontal cortex (mPFC). Previous studies have shown that both the RE and the PRC are involved in the acquisition of trace fear conditioning. However, the respective contribution of the two regions is unclear. In this study, we used pharmacological approach to compare their roles. Our data suggested that inactivation of the RE or the PRC during conditioning partially impaired, whereas inactivation of both areas totally abolished, the encoding of trace fear. We next examined whether the impaired encoding of trace fear under RE inactivation can be rescued with enhanced cholinergic tone in the PRC, and vice versa. Against our hypothesis, regardless of whether the RE was on-line or not, animals failed to encode trace fear when further engaging cholinergic activities in the PRC. Conversely, depending on PRC activation level during conditioning, further recruiting cholinergic activities in the RE led to a down-shift of fear response during retrieval. Our results revealed that the RE and the PRC were necessary for the encoding of trace fear. Moreover, there was differential importance of cholinergic modulation during the process.

Word Learning by Preschool-Age Children With Developmental Language Disorder: Impaired Encoding and Robust Consolidation During Slow Mapping.

Purpose Learning novel words, including the specific phonemes that make up word forms, is a struggle for many individuals with developmental language disorder (DLD). Building robust representations of words includes encoding during periods of input and consolidation between periods of input. The primary purpose of the current study is to determine differences between children with DLD and with typical development (TD) in the encoding and consolidation of word forms during the slow mapping process. Method Preschool-age children (DLD = 9, TD = 9) were trained on nine form-referent pairs across multiple consecutive training days. Children's ability to name referents at the end of training days indicated their ability to encode forms. Children's ability to name referents at the beginning of training days after a period of overnight sleep indicated their ability to consolidate forms. Word learning was assessed 1 month after training to determine long-term retention of forms. Results Throughout training, children with DLD produced fewer forms correctly and produced forms with less phonological precision than children with TD. Thus, children with DLD demonstrated impaired encoding. However, children with and without DLD demonstrated a similar ability to consolidate forms between training days and to retain forms across a 1-month delay. Conclusions Difficulties with word form learning are primarily driven by deficits in encoding for children with DLD. Clinicians and educators can support encoding by providing children with adequate exposures to target words via robust training that occurs across multiple sessions. Supplemental Material https://doi.org/10.23641/asha.16746454.

Negative Effects of Embodiment in a Visuo-Spatial Working Memory Task in Children, Young Adults, and Older Adults.

Studies examining the effect of embodied cognition have shown that linking one’s body movements to a cognitive task can enhance performance. The current study investigated whether concurrent walking while encoding or recalling spatial information improves working memory performance, and whether 10-year-old children, young adults, or older adults (Mage = 72 years) are affected differently by embodiment. The goal of the Spatial Memory Task was to encode and recall sequences of increasing length by reproducing positions of target fields in the correct order. The nine targets were positioned in a random configuration on a large square carpet (2.5 m × 2.5 m). During encoding and recall, participants either did not move, or they walked into the target fields. In a within-subjects design, all possible combinations of encoding and recall conditions were tested in counterbalanced order. Contrary to our predictions, moving particularly impaired encoding, but also recall. These negative effects were present in all age groups, but older adults’ memory was hampered even more strongly by walking during encoding and recall. Our results indicate that embodiment may not help people to memorize spatial information, but can create a dual-task situation instead.

A-17 Self-Generation Improves Prospective Memory Performance in Individuals with Moderate–Severe Traumatic Brain Injury

Abstract Objective Self-generation has long been studied in healthy adults as a method to improve encoding of new information. The present study applied this strategy to prospective memory (PM; the ability to remember future intentions) in individuals with traumatic brain injury (TBI). Method Participants included 17 healthy adults and 34 individuals with moderate–severe TBI, who were at least one year post-injury and impaired encoding on a test of verbal learning. Participants completed a 15-minute computer-based lexical decision task in which PM trials were embedded. Following a baseline block of 100 lexical decision trials, participants completed 2 blocks with 5 p.m. targets each. PM targets were learned in a didactic or self-generated fashion using semantically-related word pairs, counterbalanced for order effects. Results MANOVAs were conducted for PM accuracy and recognition, with performance in the didactic and self-generation conditions as within-subjects variables and diagnostic group as the between-subjects variable. Only the within-subjects variables were significant [PM accuracy: F(1,49) = 5.228, p = 0.027; PM recognition: F(1,49) = 7.226, p = 0.010]. Within the TBI sample, paired t-tests demonstrated significantly improved PM accuracy [t(33) = −2.069, p = 0.046, Hedge’s g = 0.38] and PM target recognition [t(33) = −2.458, p = 0.019, Hedge’s g = 0.52] under self-generated compared to didactic conditions. Conclusion Results indicate that self-generation is an efficacious strategy to improve PM in individuals with moderate–severe TBI and encoding deficits. The lack of interaction suggests that the generation effect is robust enough to provide comparable benefit to both individuals with significant neurocognitive deficits as well as healthy adults. Future efforts should explore the incorporation of self-generation in cognitive rehabilitation protocols for PM in neurologic populations.

Complement-associated loss of CA2 inhibitory synapses in the demyelinated hippocampus impairs memory

The complement system is implicated in synapse loss in the MS hippocampus, but the functional consequences of synapse loss remain poorly understood. Here, in post-mortem MS hippocampi with demyelination we find that deposits of the complement component C1q are enriched in the CA2 subfield, are linked to loss of inhibitory synapses and are significantly higher in MS patients with cognitive impairments compared to those with preserved cognitive functions. Using the cuprizone mouse model of demyelination, we corroborated that C1q deposits are highest within the demyelinated dorsal hippocampal CA2 pyramidal layer and co-localized with inhibitory synapses engulfed by microglia/macrophages. In agreement with the loss of inhibitory perisomatic synapses, we found that Schaffer collateral feedforward inhibition but not excitation was impaired in CA2 pyramidal neurons and accompanied by intrinsic changes and a reduced spike output. Finally, consistent with excitability deficits, we show that cuprizone-treated mice exhibit impaired encoding of social memories. Together, our findings identify CA2 as a critical circuit in demyelinated intrahippocampal lesions and memory dysfunctions in MS.

Consequence of stroke for feature recall and binding in visual working memory

Visual memory for objects involves the integration, or binding, of individual features into a coherent representation. We used a novel approach to assess feature binding, using a delayed-reproduction task in combination with computational modeling and lesion analysis. We assessed stroke patients and neurotypical controls on a visual working memory task in which spatial arrays of colored disks were presented. After a brief delay, participants either had to report the color of one disk cued by its location or the location of one disk cued by its color. Our results demonstrate that, in the controls, report imprecision and swap errors (non-target reports) can be explained by a single source of variability. Stroke patients showed an overall decrease in memory precision for both color and location, with only limited evidence for deviations from the predicted relationship between report precision and swap errors. These deviations were primarily deficits in reporting items rather than selecting items based on the cue. Atlas-based lesion-symptom mapping showed that selection and reporting deficits, precision in reporting color, and precision in reporting location were associated with different lesion profiles. Deficits in binding are associated with lesions in the left somatosensory cortex, deficits in the precision of reporting color with bilateral fronto-parietal regions, and no anatomical substrates were identified for precision in reporting location. Our results converge with previous reports that working memory representations are widely distributed in the brain and can be found across sensory, parietal, temporal, and prefrontal cortices. Stroke patients demonstrate mostly subtle impairments in visual working memory, perhaps because representations from different areas in the brain can partly compensate for impaired encoding in lesioned areas. These findings contribute to understanding of the relation between memorizing features and their bound representations.

Word learning and verbal working memory in children with developmental language disorder.

Previous research into word learning in children with developmental language disorder (DLD) indicates that the learning of word forms and meanings, rather than form-referent links, is problematic. This difficulty appears to arise with impaired encoding, while retention of word knowledge remains intact. Evidence also suggests that word learning skills may be related to verbal working memory. We aimed to substantiate these findings in the current study by exploring word learning over a series of days. Fifty children with DLD (mean age 6; 11, 72% male) and 54 age-matched typically developing (TD) children (mean age 6; 10, 56% male) were taught eight novel words across a four-day word learning protocol. Day 1 measured encoding, Days 2 and 3 measured re-encoding, and Day 4 assessed retention. At each day, word learning success was evaluated using Naming, Recognition, Description, and Identification tasks. Children with DLD showed comparable performance to the TD group on the Identification task, indicating an intact ability to learn the form-referent links. In contrast, children with DLD performed significantly worse for Naming and Recognition (signifying an impaired ability to learn novel word forms), and for Description, indicating problems establishing new word meanings. These deficits for the DLD group were apparent at Days 1, 2, and 3 of testing, indicating impairments with initial encoding and re-encoding; however, the DLD and TD groups demonstrated a similar rate of learning. All children found the retention assessments at Day 4 difficult, and there were no significant group differences. Finally, verbal working memory emerged as a significant moderator of performance on the Naming and Recognition tasks, such that children with DLD and poor verbal working memory had the lowest levels of accuracy. This study demonstrates that children with DLD struggle with learning novel word forms and meanings, but are unimpaired in their ability to establish new form-referent links. The findings suggest that the word learning deficit may be attributed to problems with encoding, rather than with retention, of new word knowledge; however, further exploration is required given the poor performance of both groups for retention testing. Furthermore, we found evidence that an impaired ability to learn word forms may only be apparent in children who have DLD and low levels of verbal working memory. When working with children with DLD, speech-language pathologists should assess word learning using tasks that evaluate the ability to learn word forms, meanings, and form-referent links to develop a profile of individual word learning strengths and weaknesses. Clinicians should also assess verbal working memory to identify children at particular risk of word learning deficits. Future research should explore the notion of optimal intervention intensity for facilitating word learning in children with poor language and verbal working memory.

Visual working memory deficits following right brain damage

Visual working memory (VWM) involves the encoding and maintenance of visual information over time, with the requirement that object features be accurately bound to spatial locations. We and others have shown that damage to the right hemisphere leads to impaired spatial working memory. Here, we test the notion that right brain damage (RBD) may have consequences for domain general VWM. We had eight RBD patients and a group of healthy control participants perform a VWM task under different loads (1 to 3 items to recall) and spatial competition (high vs. low). All participants were asked to remember the colour of target items presented on the right side of space. Patients showed impaired encoding of information evident in poor precision of memory representations and increased guessing rates even at a set size of only one item. Our data suggests that VWM capacity is severely limited following RBD. Although five of the eight patients presented with neglect, it is not clear whether this deficit in VWM is unique to the syndrome. We suggest that future work should directly pit attention and VWM demands against one another in the same patients to determine whether the confluence of deficits in these domains is the critical determinant of the neglect syndrome. Regardless of the implications for the neglect syndrome, however, our data show that VWM deficits in RBD patients extend into non-spatial feature space.

Transcranial Direct Current Stimulation over the Prefrontal Cortex Alters Encoding and Judgments of Learning Based on Fluency.

Past research has shown that judgments of learning (JOLs), subjective confidence judgments made at study about later memorability, are inferential in nature and based on cues available during encoding. Participants tend to use fluency as a cue and give higher JOLs to more fluently encoded items, despite having better recognition memory for disfluently encoded items, which leads to poor JOL accuracy. Research has implicated the dorsolateral prefrontal cortex (DLPFC) and anterior prefrontal cortex (aPFC) in JOL and encoding processes, but no studies to date have tested how the roles of these regions vary with the information on which JOLs are based. We used high-definition transcranial direct current stimulation to test the causal roles of DLPFC and aPFC in encoding success, JOL ratings, and JOL accuracy. Participants studied and made JOLs about words that varied in fluency (i.e., frequency and orientation). High-definition transcranial direct current stimulation over the DLPFC impaired encoding, as evidenced by an increase in subsequent false alarms. For words that were less fluently encoded, aPFC stimulation improved JOL accuracy, perhaps making participants more aware of encoding failures under conditions of disfluency. Conversely, DLPFC and aPFC stimulation decreased JOL accuracy for high-frequency words, suggesting the roles of these regions in JOLs vary with the cognitive bases of the judgments. These results contribute to our understanding of the causal roles of prefrontal regions in objective and subjective memory processes and how their contributions to metamemory accuracy vary with information on which subjective assessments are based.

The NMDA receptor antagonist MK-801 fails to impair long-term recognition memory in mice when the state-dependency of memory is controlled.

NMDA receptor-dependent synaptic plasticity has been proposed to be important for encoding of memories. Consistent with this hypothesis, the non-competitive NMDA receptor antagonist, MK-801, has been found to impair performance on tests of memory. Interpretation of some of these findings has, however, been complicated by the fact that the drug-state of animals has differed during encoding and tests of memory. Therefore, it is possible that MK-801 may result in state-dependent retrieval or expression of memory rather than actually impairing encoding itself. We tested this hypothesis in mice using tests of object recognition memory with a 24-hour delay between the encoding and test phase. Mice received injections of either vehicle or MK-801 prior to the encoding phase and the test phase. In Experiment 1, a low dose of MK-801 (0.01 mg/kg) impaired performance when the drug-state (vehicle or MK-801) of mice changed between encoding and test, but there was no significant effect of MK-801 on encoding. In Experiment 2, a higher dose of MK-801 (0.1 mg/kg) failed to impair object recognition memory when mice received the drug prior to both encoding and test compared to mice that received vehicle. MK-801 did not affect object exploration, but it did induce locomotor hyperactivity at the higher dose. These results suggest that some previous demonstrations of MK-801 effects may reflect a failure to express or retrieve memory due to the state-dependency of memory rather than impaired encoding of memory.

Developmental hearing loss in conjunction with early life stress: Perceptual deficits and central auditory correlates

In children with otitis media, the conductive hearing loss (CHL) accompanying infection is a risk factor for later problems with speech perception. These perceptual deficits can persist long after auditory thresholds return to normal, suggesting they may be mediated by changes within the central auditory system. Using animal models of developmental CHL, we have demonstrated perceptual deficits for several temporally-varying signals that comprise speech. Furthermore, these perceptual deficits are correlated with impaired encoding in auditory cortex, indicating that central changes emerge from early auditory deprivation. In our transient developmental CHL model, which mimics the intermittent bouts of hearing loss experienced by children with otitis media, deficits are much alleviated by adulthood. However, early-life stress (ELS) has been described as an additional risk factor for speech problems arising from otitis media. Our data indicate that ELS alone induces deficits in the perception of temporally varying signals. Furthermore, animals experiencing both early transient CHL and ELS have perceptual deficits lasting into adulthood, the magnitude of which is greater than the sum of the individual deficits. These results raise the possibility that early life stress, alone or in conjunction with early CHL, may adverely impact speech perception in humans.

Moving beyond summary scores: Decomposing free recall performance to understand episodic memory deficits in schizotypy.

Negative symptom schizophrenia and negative schizotypy are associated with deficits in episodic memory, which may reflect deficits in context processing. However, studies that rely on summary performance measures such as mean accuracy or latency are limited in the extent that they can examine processes underlying memory impairment. The present study decomposed free recall performance by examining serial position functions, first response probability, temporal contiguity effect, cumulative recall functions, and interresponse times in high-positive schizotypy, high-negative schizotypy, and control groups. The negative schizotypy group exhibited not only impaired overall free recall performance but also a pattern of deficits consistent with impaired context processing on the underlying measures. Specifically, the negative schizotypy group was less likely than the other groups to initiate recall with the first item in the list, suggesting impaired encoding or reinstatement of context, and also showed reduced temporal contiguity compared with the other groups, suggesting diminished temporal organization. The cumulative recall function indicated that the negative schizotypy group experienced disruptions in both the sampling and recovery stages of retrieval. Finally, the negative schizotypy group experienced greater slowing between the responses during retrieval, consistent with the finding of reduced temporal contiguity and indicating that it likely terminated memory search before the remaining groups. The positive schizotypy and control groups did not differ on any of the measures. The finding that context-processing deficits occur in both subclinical negative schizotypy and negative symptom schizophrenia suggests that they may represent core areas of impairment in the schizophrenia spectrum. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Ripple oscillations in the left temporal neocortex are associated with impaired verbal episodic memory encoding

BackgroundWe sought to determine if ripple oscillations (80–120 Hz), detected in intracranial electroencephalogram (iEEG) recordings of patients with epilepsy, correlate with an enhancement or disruption of verbal episodic memory encoding. MethodsWe defined ripple and spike events in depth iEEG recordings during list learning in 107 patients with focal epilepsy. We used logistic regression models (LRMs) to investigate the relationship between the occurrence of ripple and spike events during word presentation and the odds of successful word recall following a distractor epoch and included the seizure onset zone (SOZ) as a covariate in the LRMs. ResultsWe detected events during 58,312 word presentation trials from 7630 unique electrode sites. The probability of ripple on spike (RonS) events was increased in the SOZ (p < 0.04). In the left temporal neocortex, RonS events during word presentation corresponded with a decrease in the odds ratio (OR) of successful recall, however, this effect only met significance in the SOZ (OR of word recall: 0.71, 95% confidence interval (CI): 0.59–0.85, n = 158 events, adaptive Hochberg, p < 0.01). Ripple on oscillation (RonO) events that occurred in the left temporal neocortex non-SOZ also correlated with decreased odds of successful recall (OR: 0.52, 95% CI: 0.34–0.80, n = 140, adaptive Hochberg, p < 0.01). Spikes and RonS that occurred during word presentation in the left middle temporal gyrus (MTG) correlated with the most significant decrease in the odds of successful recall, irrespective of the location of the SOZ (adaptive Hochberg, p < 0.01). ConclusionRipples and spikes generated in the left temporal neocortex are associated with impaired verbal episodic memory encoding. Although physiological and pathological ripple oscillations were not distinguished during cognitive tasks, our results show an association of undifferentiated ripples with impaired encoding. The effect was sometimes specific to regions outside the SOZ, suggesting that widespread effects of epilepsy outside the SOZ may contribute to cognitive impairment.

Sensory Processing Phenotypes in Fragile X Syndrome.

Fragile X syndrome (FXS) is a neurodevelopmental disorder that causes intellectual disability. It is a leading known genetic cause of autism. In addition to cognitive, social, and communication deficits, humans with FXS demonstrate abnormal sensory processing including sensory hypersensitivity. Sensory hypersensitivity commonly manifests as auditory, tactile, or visual defensiveness or avoidance. Clinical, behavioral, and electrophysiological studies consistently show auditory hypersensitivity, impaired habituation to repeated sounds, and reduced auditory attention in humans with FXS. Children with FXS also exhibit significant visuospatial impairments. Studies in infants and toddlers with FXS have documented impairments in processing texture-defined motion stimuli, temporal flicker, perceiving ordinal numerical sequence, and the ability to maintain the identity of dynamic object information during occlusion. Consistent with the observations in humans with FXS, fragile X mental retardation 1 (Fmr1) gene knockout (KO) rodent models of FXS also show seizures, abnormal visual-evoked responses, auditory hypersensitivity, and abnormal processing at multiple levels of the auditory system, including altered acoustic startle responses. Among other sensory symptoms, individuals with FXS exhibit tactile defensiveness. Fmr1 KO mice also show impaired encoding of tactile stimulation frequency and larger size of receptive fields in the somatosensory cortex. Since sensory deficits are relatively more tractable from circuit mechanisms and developmental perspectives than more complex social behaviors, the focus of this review is on clinical, functional, and structural studies that outline the auditory, visual, and somatosensory processing deficits in FXS. The similarities in sensory phenotypes between humans with FXS and animal models suggest a likely conservation of basic sensory processing circuits across species and may provide a translational platform to not just develop biomarkers but also to understand underlying mechanisms. We argue that preclinical studies in animal models of FXS can facilitate the ongoing search for new therapeutic approaches in FXS by understanding mechanisms of basic sensory processing circuits and behaviors that are conserved across species.

Dehydroepiandrosterone impacts working memory by shaping cortico-hippocampal structural covariance during development

Existing studies suggest that dehydroepiandrosterone (DHEA) may be important for human brain development and cognition. For example, molecular studies have hinted at the critical role of DHEA in enhancing brain plasticity. Studies of human brain development also support the notion that DHEA is involved in preserving cortical plasticity. Further, some, though not all, studies show that DHEA administration may lead to improvements in working memory in adults. Yet these findings remain limited by an incomplete understanding of the specific neuroanatomical mechanisms through which DHEA may impact the CNS during development. Here we examined associations between DHEA, cortico-hippocampal structural covariance, and working memory (216 participants [female=123], age range 6–22 years old, mean age: 13.6 +/−3.6 years, each followed for a maximum of 3 visits over the course of 4 years). In addition to administering performance-based, spatial working memory tests to these children, we also collected ecological, parent ratings of working memory in everyday situations. We found that increasingly higher DHEA levels were associated with a shift toward positive insular-hippocampal and occipito-hippocampal structural covariance. In turn, DHEA-related insular-hippocampal covariance was associated with lower spatial working memory but higher overall working memory as measured by the ecological parent ratings. Taken together with previous research, these results support the hypothesis that DHEA may optimize cortical functions related to general attentional and working memory processes, but impair the development of bottom-up, hippocampal-to-cortical connections, resulting in impaired encoding of spatial cues.

Dexamethasone impairs encoding and expression of aversive conditioning promoted by pentylenetetrazole.

Behavioral and neuroendocrine responses following threatening situations promote the release of corticosterone, which is known to modulate trauma-related learning and memory process. However, it remains unknown whether the aversive learning generated by interoceptive fear conditioning is affected by glucocorticoid modulation. Therefore, the present study aimed to investigate the role of dexamethasone suppression in encoding and expression of pentylenetetrazole-induced olfactory fear conditioning (OFC) and in contextual second-order conditioning promoted by the conditioned odor. Adult male Long-Evans rats were treated with dexamethasone 60 min before the encoding or the expression in both OFC and contextual second-order conditioning. Dexamethasone treatment impaired encoding and expression of the OFC, but failed to impair encoding and expression of the contextual second-order conditioning. Altogether, our results show that although OFC and thereafter contextual second-order conditioning may allow the study of traumatic memories, each order of conditioning seems to present specific features related to their pharmacological modulation. These findings highlight the importance of addressing the role of neuromodulatory systems in first-order and second-order conditioning to gain a better understanding of these phenomena and support future therapies related to traumatic memories.