Biphasic ERK1/2 activation in both the hippocampus and amygdala may reveal a system consolidation of contextual fear memory

There is accumulating evidences to suggest that memory consolidation in some conditions involves two waves of neuronal plastic change. Using two fear conditioning procedures in male C57BL/6J mice, we have recently shown that consolidation of the foreground contextual fear memory required two waves of ERK1/2 activation in hippocampal CA1, while consolidation of cue conditioning was only associated with the early phase of activation. The present experiment further showed that this bi-phasic pattern of ERK1/2 activation was not restricted to hippocampal CA1, but could also be observed in other fear memory-related brain areas. The unpaired conditioning procedure (context in foreground) induced two waves of ERK1/2 activation in hippocampal CA1 and CA3, as well as in the LA and BLA nuclei of the amygdala. In contrast, the paired conditioning procedure (context in background) led to a transient early phase only in hippocampal CA1 and LA. In addition, ERK1/2 phosphorylation in the hippocampus was found to correlate with that in the amygdala nuclei specifically after the unpaired procedure. Taken together, our data suggest that the observed biphasic pattern of neuronal plastic events may reflect the interplay between hippocampal and amygdala activity-dependent plasticity critical for the system consolidation of contextual fear memory.     

Cognition and lobar morphology in full mutation boys with fragile X syndrome

The aims of the present study are twofold: (1) to examine cortical morphology (CM) associated with alterations in cognition in fragile X syndrome (FXS); (2) to characterize the CM profile of FXS versus FXS with an autism diagnosis (FXS + Aut) as a preliminary attempt to further elucidate the behavioral distinctions between the two sub-groups. We used anatomical magnetic resonance imaging surface-based morphometry in 21 male children (FXS N = 11 and age [2.27-13.3] matched controls [C] N = 10). We found (1) increased whole hemispheric and lobar cortical volume, cortical thickness and cortical complexity bilaterally, yet insignificant changes in hemispheric surface area and gyrification index in FXS compared to C; (2) linear regression analyses revealed significant negative correlations between CM and cognition; (3) significant CM differences between FXS and FXS + Aut associated with their distinctive behavioral phenotypes. These findings are critical in understanding the neuropathophysiology of one of the most common intellectual deficiency syndromes associated with altered cognition as they provide human in vivo information about genetic control of CM and cognition.     

Dynamic testing of learning potential in adults with cognitive impairments: A systematic review of methodology and predictive value

Dynamic testing includes procedures that examine the effects of brief training on test performance where pre‐ to post‐training change reflects patients’ learning potential. The objective of this systematic review was to provide clinicians and researchers insight into the concept and methodology of dynamic testing and to explore its predictive validity in adult patients with cognitive impairments. The following electronic databases were searched: PubMed, PsychINFO, and Embase/Medline. Of 1141 potentially relevant articles, 24 studies met the inclusion criteria. The mean methodological quality score was 4.6 of 8. Eleven different dynamic tests were used. The majority of studies used dynamic versions of the Wisconsin Card Sorting Test. The training mostly consisted of a combination of performance feedback, reinforcement, expanded instruction, or strategy training. Learning potential was quantified using numerical (post‐test score, difference score, gain score, regression residuals) and categorical (groups) indices. In five of six longitudinal studies, learning potential significantly predicted rehabilitation outcome. Three of four studies supported the added value of dynamic testing over conventional testing in predicting rehabilitation outcome. This review provides preliminary support that dynamic tests can provide a valuable addition to conventional tests to assess patients’ abilities. Although promising, there was a large variability in methods used for dynamic testing and, therefore, it remains unclear which dynamic testing methods are most appropriate for patients with cognitive impairments. More research is warranted to further evaluate and refine dynamic testing methodology and to further elucidate its predictive validity concerning rehabilitation outcomes relative to other cognitive and functional status indices.     

Size of the neocerebellar vermis is associated with cognition in healthy elderly men

Cerebellar volumes show small positive correlations with cognitive ability in young adults, but no studies have examined this relationship in older adults. Furthermore, no studies have examined relationships between sizes of subareas of the cerebellum and cognitive ability. We hypothesized that size of the two areas of the neocerebellar vermis would correlate with a battery of eight cognitive tests in 50 men aged 65-70. Size of the neocerebellar areas of the vermis correlated positively with several cognitive tests (r's=.29-.37, p<.05), whilst sizes of other parts of the vermis did not correlate with any cognitive tests. Total cerebellar volumes correlated significantly with a test of nonverbal reasoning (r=.030, p=.42). These findings suggest a specific association of neocerebellar vermis size with variations in cognitive ability in older adults.     

Trait impulsiveness and executive function in healthy young adults

Performance-based neuropsychological tests are often used to assess planning and impulse control, but the extent to which these measures reflect trait impulsiveness or specific dimensions of trait impulsiveness is not clear. This study used the Barratt Impulsiveness Scale-11 (BIS-11; [Patton, J. H., Stanford, M. S., & Barratt, E. S. (1995). Factor structure of the Barratt Impulsiveness Scale. Journal of Clinical Psychology, 51, 768–774.]) to examine the relationship between various dimensions of trait impulsiveness and performance on several executive function tests in healthy young adults. Total BIS-11 scores correlated with performance on measures of planning and impulse control. Higher non-planning impulsiveness scores, which indicate poorer self-control and lower cognitive complexity, correlated most strongly with performance on a maze test that measures planning and impulse control (r = .58). These results provide support for the convergent validity of pencil-and-paper maze-based measures of planning and impulse control.     

Influence of IQ in interpreting MMSE scores in patients with multiple sclerosis

The Mini-Mental State Examination (MMSE) and Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) were administered to 46 outpatients diagnosed with multiple sclerosis (MS). MMSE total raw score was significantly and positively correlated with all WAIS-IV indexes, even when controlling for the effects of participant educational level, with the strongest relationship being with Full Scale IQ. These results suggest that clinicians consider patient intellectual functioning, in particular Full Scale IQ, when diagnosing neurocognitive impairment based on screening with the MMSE in individuals with MS.     

Unimpaired performance during cognitive and visual manipulations in persons with anterior cruciate ligament reconstruction compared to healthy adults

Emerging research has proposed an increased reliance on visual processing and cognitive faculties in persons following anterior cruciate ligament reconstruction (ACLR). ACLR individuals display increased activation of visual and cognitive processing brain areas during task execution and exhibit dramatic performance decrements when vision is removed or cognitive difficulty is increased. Despite these intriguing findings, no previous studies have comprehensively assessed performance-related outcomes during tasks that challenge the cognitive and visual systems in ACLR individuals. The following hypotheses were proposed: 1) ACLR individuals will perform better on cognitive tests that required visual scanning; 2) ACLR individuals will utilize visual biofeedback when available during a proprioceptive task but experience decrements in performance when visual biofeedback is removed; and 3) during a cognitive-motor dual-task, the motor task will be more attentionally demanding for ACLR individuals compared to controls, whereas cognitive dual-task effects will be similar between groups. Twenty-one individuals with ACLR and 21 matched healthy adults performed a series of cognitive tests (Stroop, Trail Making Test, and NIH EXAMINER Battery), as well as a single-task angle-matching paradigm with and without visual biofeedback and a dual-task angle-matching paradigm with varying levels of visual and cognitive difficulty. ACLR individuals performed similarly on cognitive tasks, regardless of visual scanning requirements, demonstrated similar proprioceptive performance, evident via similar drift during the single-task conditions, and exhibited similar dual-task effects when the angle-matching paradigm was performed concurrently with a cognitive test compared to healthy adults. Despite a growing literature suggesting alterations to visual and cognitive system utilization in ACLR individuals, the current investigation found a subset of ACLR individuals do not exhibit this performance.     

Subjective cognitive complaint in healthy older adults: Identification of major domains and relation to objective performance

This study analyzed complaints across a range of memory domains in middle-aged and older adults, as well as assessed their relationship with objective cognitive performance and personal characteristics. A total of 115 community-dwelling, healthy adults between the ages of 45 and 87 completed the Self-Evaluation Questionnaire (QAM) and were tested with a comprehensive neuropsychological battery. A principal component analysis identified seven dimensions of complaint. Difficulty inhibiting internal and external sources of interference when learning or remembering something was the main area of complaint and it was correlated with word-list recall and Digit Symbol. We identified complaints related to a set of memory failures that appear to be more detrimental to autonomy and safety. These were correlated with a measure of functional autonomy and might, therefore, indicate more severe difficulties. Overall, this study provides indications regarding the main domains of memory complaints and identifies which complaints are most reflective of objective cognitive problems.     

Kindling-induced changes in plasticity of the rat amygdala and hippocampus

Temporal lobe epilepsy (TLE) is often accompanied by interictal behavioral abnormalities, such as fear and memory impairment. To identify possible underlying substrates, we analyzed long-term synaptic plasticity in two relevant brain regions, the lateral amygdala (LA) and the CA1 region of the hippocampus, in the kindling model of epilepsy. Wistar rats were kindled through daily administration of brief electrical stimulations to the left basolateral nucleus of the amygdala. Field potential recordings were performed in slices obtained from kindled rats 48 h after the last induced seizure, and in slices from sham-implanted and nonimplanted controls. Kindling resulted in a significant impairment of long-term potentiation (LTP) in both the LA and the CA1, the magnitude of which was dependent on the number of prior stage V seizures. Saturation of CA1-LTP, assessed through repeated spaced delivery of high-frequency stimulation, occurred at lower levels in kindled compared to sham-implanted animals, consistent with the hypothesis of reduced capacity of further synaptic strengthening. Furthermore, theta pulse stimulation elicited long-term depression in the amygdala in nonimplanted and sham-implanted controls, whereas the same stimulation protocol stimulation caused LTP in kindled rats. In conclusion, kindling differentially affects the magnitude, saturation, and polarity of LTP in the CA1 and LA, respectively, most likely indicating an activity-dependent mechanism in the context of synaptic metaplasticity.     

Self-generation amplifies the errorless learning effect in healthy older adults when transfer appropriate processing conditions are met

ABSTRACT

Older adults have considerable impairment in associative recognition despite minimal age differences in item recognition. The magnitude of this associative deficit varies by type of stimuli, strategy utilization, and other mediators and moderators (Old &; Naveh-Benjamin, 2008 Old, S. R., &; Naveh-Benjamin, M. (2008). Differential effects of age on item and associative measures of memory: A meta-analysis. Psychology and Aging, 23, 104–118. doi: 10.1037/0882-7974.23.1.104[Crossref], [PubMed], [Web of Science ®] , [Google Scholar], Psychology and Aging, 23, 104–118). Name pair stimuli have not been used to test the associative deficit hypothesis (ADH), although tests using name–face stimuli support the ADH. Additionally, metacognitive awareness of the ADH has not been investigated. We tested the ADH with word and name pair stimuli, and predicted that age-related associative deficits would be larger for words than names because names, unlike most common nouns, lack certain semantic properties that could be used to bind pairs of names together. Results supported the ADH for words but not names: Younger and older adults recognized equivalently fewer names on the associative test relative to the item test. As predicted, self-efficacy was higher for younger than older adults. Surprisingly, self-efficacy for the associative test was higher than for the item test but post-test estimates of performance success (postdictions) were higher for the item test than for the associative test, suggesting sensitivity by participants to different task demands in the item and associative tests following recognition attempts. Metacognitive accuracy was better for words than names and for the item test than associative test, and equivalent between age groups. Overall, participants overestimated their name recognition abilities. Our findings extend support for the ADH to a conceptually important and ecologically valid domain (names) and provide new data on metacognitive aspects of the ADH.     

Auditory specific fear conditioning results in increased levels of synaptophysin in the basolateral amygdala

Auditory fear conditioning is one of the most well characterized models used in studies of learning and memory. In order to ensure the animals have been conditioned to fear the auditory stimulus, animals are generally tested for their response to this stimulus in a different context to that used for training. For this reason it is often unclear how much contextual fear conditioning the animals also acquire when they are trained. In this study, we have established a protocol for fear conditioning in mice which is explicit for auditory cues; mice trained using this protocol, show a very low fear response to contextual cues encountered during training. We have undertaken analysis to look for potential brain changes associated with this model by measuring levels of the synaptic vesicle protein, synaptophysin, in the basolateral nuclei of the amygdala following auditory fear conditioning. Our results show levels of synaptophysin were significantly higher in mice which learnt to associate the auditory stimulus with fear, in comparison to all non-learning control animals. These findings support the idea that synaptic plasticity associated with formation of fear conditioning to a single specific conditioned stimulus occurs within the basolateral nuclei of the amygdala. Furthermore, our results demonstrate the usefulness of this model in looking for changes in the brain specific for a defined learning event.     

Lidocaine attenuates anisomycin-induced amnesia and release of norepinephrine in the amygdala

When administered near the time of training, protein synthesis inhibitors such as anisomycin impair later memory. A common interpretation of these findings is that memory consolidation requires new protein synthesis initiated by training. However, recent findings support an alternative interpretation that abnormally large increases in neurotransmitter release after injections of anisomycin may be responsible for producing amnesia. In the present study, a local anesthetic was administered prior to anisomycin injections in an attempt to mitigate neurotransmitter actions and thereby attenuate the resulting amnesia. Rats received lidocaine and anisomycin injections into the amygdala 130 and 120 min, respectively, prior to inhibitory avoidance training. Memory tests 48 h later revealed that lidocaine attenuated anisomycin-induced amnesia. In other rats, in vivo microdialysis was performed at the site of amygdala infusion of lidocaine and anisomycin. As seen previously, anisomycin injections produced large increases in release of norepinephrine in the amygdala. Lidocaine attenuated the anisomycin-induced increase in release of norepinephrine but did not reverse anisomycin inhibition of protein synthesis, as assessed by c-Fos immunohistochemistry. These findings are consistent with past evidence suggesting that anisomycin causes amnesia by initiating abnormal release of neurotransmitters in response to the inhibition of protein synthesis.     

Parent rating of executive function in fetal alcohol spectrum disorder: A review of the literature and new data on Aboriginal Canadian children

Aboriginal children in Canada are at high risk of fetal alcohol spectrum disorder (FASD) but there is little research on the cognitive impact of prenatal alcohol exposure (PAE) in this population. This paper reviews the literature on parent report of executive functioning in children with FASD that used the Behavior Rating Inventory of Executive Function (BRIEF). New data on the BRIEF is then reported in a sample of 52 Aboriginal Canadian children with FASD for whom a primary caregiver completed the BRIEF. The children also completed a battery of neuropsychological tests. The results reveal mean scores in the impaired range for all three BRIEF index scores and seven of the eight scales, with the greatest difficulties found on the Working Memory, Inhibit and Shift scales. The majority of the children were reported as impaired on the index scores and scales, with Working Memory being most commonly impaired scale. On the performance-based tests, Trails B and Letter Fluency are most often reported as impaired, though the prevalence of impairment is greater for parent ratings than test performance. No gender difference is noted for the parent report, but the boys had slightly slower intellectual functioning and were more perseverative than the girls on testing. The presence of psychiatric comorbidity is unrelated to either BRIEF or test scores. These findings are generally consistent with prior studies indicating that parents observe considerable executive dysfunction in children with FASD, and that children with FASD may have more difficulty with executive functions in everyday life than is detected by laboratory-based tests alone.     

Functional connectivity abnormalities vary by amygdala subdivision and are associated with psychiatric symptoms in unilateral temporal epilepsy

The amygdala has been described as a structure affected by mesial temporal lobe epilepsy (MTLE). Indeed, it is suggested that amygdala abnormalities are related to the co-morbid depression and anxiety reported in MTLE. In this context, we investigated the relation between functional connectivity (FC) emerging from this structure in fMRI and depression and anxiety levels reported in MTLE patients. We focused on resting-state BOLD activity and evaluated whether FC differences emerge from each of three amygdala subdivisions (laterobasal, centromedial and superficial) in left and right MTLE groups, compared with healthy controls. Results revealed significant differences between patient groups and controls. Specifically, the left MTLE group showed abnormal FC for the left-sided seeds only. Furthermore, regardless of the seed, we observed more reliable differences between the right MTLE group and controls. Further analysis of these results revealed correlations between these impaired connectivities and psychiatric symptoms in both MTLE groups. Opposite relations, however, were highlighted: the more depressed or anxious the right MTLE patients, the closer their FC values approached controls; whereas the less anxious the left MTLE patients, the closer their FC values were normative. These results highlight how MTLE alter FC emerging from the limbic system. Overall, our data demonstrate that right TLE has a more maladaptive impact on emotion-related networks, in ways specific to the amygdala region, and the emotion symptom involved, than left TLE.     

Executive functions and social skills in survivors of pediatric brain tumor

Medical advances have resulted in increased survival rates for children with brain tumors. Consequently, issues related to survivorship have become more critical. The use of multimodal treatment, in particular cranial radiation therapy, has been associated with subsequent cognitive decline. Specifically, deficits in executive functions have been reported in survivors of various types of pediatric brain tumor. Survivors are left with difficulties, particularly in self-monitoring, initiation, inhibition, and planning, to name a few. Another domain in which survivors of pediatric brain tumor have been reported to show difficulty is that of social skills. Parents, teachers, and survivors themselves have reported decreased social functioning following treatment. Deficits in executive functions and social skills are likely interrelated in this population, as executive skills are needed to navigate various aspects of social interaction; however, this has yet to be studied empirically. Twenty-four survivors of pediatric brain tumor were assessed using a computerized task of executive functions, as well as paper-and-pencil measures of social skills and real-world executive skills. Social functioning was related to a specific aspect of executive functions, that is, the survivors' variability in response time, such that inconsistent responding was associated with better parent-reported and survivor-reported social skills, independent of intellectual abilities. Additionally, parent-reported real-world global executive abilities predicted parent-reported social skills. The implications of these findings for social skills interventions and future research are discussed.     

Correlates and stability of alternate stimuli in a computer-based measure of inspection time

Inspection time tasks assess the ability to make a simple visual discrimination, typically in milliseconds. Typically, IT stimuli consists of a pi-shaped figure, in which subjects select the side with the significantly longer leg. To prevent storage in iconic memory, a backward mask is then introduced. However, some participants have reported that the mask may cause the shorter leg to appear to lengthen, creating a possible strategy that facilitates performance. As a result, alternative stimuli/masks have been developed; however, these alternative stimuli may be processed differently. This study assessed the cognitive correlates and stability of an alternative stimuli/mask. Results indicated that processing of the stimuli was influenced by an interaction between the complexity of the stimuli and the number of times it was presented. Specifically, the alternative stimulus/mask produced slower processing, particularly at the time of a second administration; however, it contributed an important and unique relationship with speeded, general intelligence.     

Memory for reward location is enhanced even though acetylcholine efflux within the amygdala is impaired in rats with damage to the diencephalon produced by thiamine deficiency

Sleep facilitates declarative memory processing. However, we know little about whether sleep plays a role in the processing of a fundamental feature of declarative memory, relational memory – the flexible representation of items not directly learned prior to sleep. Thirty-one healthy participants first learned at 12 pm two sets of face–object photograph pairs (direct associative memory), in which the objects in each pair were common to both lists, but paired with two different faces. Participants either were given approximately 90 min to have a NREM-only daytime nap (n = 14) or an equivalent waking period (n = 17). At 4:30 pm, participants who napped demonstrated significantly better retention of direct associative memory, as well as better performance on a surprise task assessing their relational memory, in which participants had to associate the two faces previously paired with the same object during learning. Particularly noteworthy, relational memory performance was correlated with the amount of NREM sleep during the nap, with only slow-wave sleep predicting relational memory performance. Sleep stage data did not correlate with direct associative memory retention. These results suggest an active role for sleep in facilitating multiple processes that are not limited to the mere strengthening of rote memories, but also the binding of items that were not directly learned together, reorganizing them for flexible use at a later time.     

Expressed emotion in families of children and adults with intellectual disabilities

Expressed emotion (EE) is a measure of the affective relationship between two people characterized by criticism, hostility, and emotionally over-involved attitudes. Outside of the field of intellectual disabilities, there has been considerable interest in EE as an environmental marker that explains variance in the severity and/or course of a number of psychiatric disorders. Researchers have also studied EE in parents and found strong associations with children's behavior problems. In this review, we focus on the data from 11 published studies of EE in families of children and adults with intellectual disabilities. We conclude that there is evidence for the presence of high EE in some families, and that this alone should concern researchers and clinicians and set an agenda for considerable future research effort. We also note a lack of attention to the measurement of EE in intellectual disability. In terms of the existing evidence base, we suggest that there is support for the hypothesis that behavior problems in children and adults with intellectual disabilities may be related to high EE in parents, and a small amount of data predicting over time support the putative causal effect of high EE on maintaining or exacerbating behavior problems. Given that EE is perhaps best conceptualized as the result of an interaction between caregivers and those cared for, there is a need to explore interventions that may help to remediate high EE within families. It is also important to understand from this position that EE may be a normative part of the experience of caring for someone under very stressful circumstances and not something for which families are blamed. Other future research priorities and some implications for practice are also discussed.     

Measuring attention in very old adults using the Test of Everyday Attention

There is a need for validated measures of attention for use in longitudinal studies of older populations. We studied 249 participants aged 80 to 101 years using the population-based MOBILIZE Boston Study. Four subscales of the Test of Everyday Attention (TEA) were included, measuring attention switching, selective, sustained and divided attention and a neuropsychological battery including validated measures of multiple cognitive domains measuring attention, executive function and memory. The TEA previously has not been validated in persons aged 80 and older. Among participants who completed the TEA, scores on other attentional measures strongly with TEA domains (R=.60-.70). Proportions of participants with incomplete TEA subscales ranged from 8% (selective attention) to 19% (attentional switching). Reasons for not completing TEA tests included failure to comprehend test instructions despite repetition and practice. These results demonstrate the challenges and potential value of the Test of Everyday Attention in studies of very old populations.     

Cognitive ability and political beliefs in the United States

Recent evidence indicates that cognitive ability has a monotonically positive relation to socially liberal beliefs and some measures of fiscally conservative beliefs, and that it has a non-monotonic relation to other measures of fiscally conservative beliefs. This study examines the relationship between cognitive ability and political beliefs in a recent, nationally representative sample of American adults. It finds that cognitive ability is positively associated with both socially liberal beliefs and fiscally conservative beliefs. The relationships with socially liberal beliefs are monotonically positive. In contrast, some of the relationships with fiscally conservative beliefs are non-monotonic: Americans of highest ability are less fiscally conservative than those of high ability. The association between cognitive ability and a dimension of fiscal conservatism is reduced substantially when controlling for socio-economic position.