Behavioral and Brain Functions - Latest articles

Similarity of DMD gene deletion and duplication in the Chinese patients compared to global populations

2008-04-29

Background: DNA deletion and duplication were determined as the major mutation underlying Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD).MethodApplying multiplex ligation-dependent probe amplification (MLPA), we have analyzed 179 unrelated DMD/BMD subjects from northern China. Results: Seventy-three percent of the subjects were found having a deletion (66.25%) or duplication (6.25%). Exons 51–52 were detected as the most common fragment deleted in single-exon deletion, and the region of exons 45–50 was the most common exons deleted in multi-exon deletions. About 90% of DMD/BMD cases carry a small size deletion that involves 10 exons or less, 26.67% of which carry a single-exon deletion. Most of the smaller deletions resulted in an out-of-frame mutation. The most common exons deleted were determined to be between exon 48 and exon 52, with exon 50 was the model allele. Verifying single-exon deletion, one sample with a deletion of exon 53 that was initially observed from MLPA showed that there was a single base deletion that abolished the ligation site in MLPA. Confirmation of single-exon deletion is recommended to exclude single base deletion or mutation at the MLPA ligation site. Conclusion: The frequency of deletion and duplication in northern China is similar to global ethnic populations.

Absence of stimulus-driven synchronization effects on sensory perception in autism: Evidence for local underconnectivity?

Mark Tommerdahl, Vinay Tannan, Jameson K Holden and Grace T Baranek — 2008-04-24

Background: A number of neurophysiological characteristics demonstrated in autism share the common theme of under-connectivity in the cerebral cortex. One of the prominent theories of the cause of the dysfunctional connectivity in autism is based on distinct anatomical structures that differ between the autistic and the neurotypical cortex. The functional minicolumn has been identified as occupying a much smaller space in the cortex of people with autism as compared to neurotypical controls, and this aberration in architecture has been proposed to lead to under-connectivity at the local or within-macrocolumn level, which in turn leads to dysfunctional connectivity globally across cortical areas in persons with autism. Numerous reports have indicated reduced synchronization of activity on a large scale in the brains of people with autism. We hypothesized that if the larger-scale aberrant dynamics in autism were due – at least in part – to a widespread propagation of the errors introduced at the level of local connectivity between minicolumns, then aberrations in local functional connectivity should also be detectable in autism. Methods: Recently, we reported a method for measuring the perceptual changes that are impacted by the presence of synchronized conditioning stimuli on the skin. In this study, the temporal order judgment (TOJ) and temporal discriminative threshold (TDT) of 10 adult autism subjects were assessed both in the absence and presence of synchronized conditioning vibrotactile stimuli. Results: Our previous report demonstrated that delivering simultaneous and synchronized vibrotactile stimuli to near-adjacent skin sites decreases a subject's ability to determine temporal order by 3 to 4-fold. However, results presented in this report show that subjects with autism do not demonstrate such decreased capacity in temporal order judgment (TOJ) in the presence of synchronized conditioning stimuli, although these same subjects do have TOJ thresholds well above that of controls. Conclusion: It is speculated that the differences in sensory perceptual capacities in the presence of synchronized conditioning stimuli in autism are due to local under-connectivity in cortex at the minicolumnar organizational level, and that the above-average TOJ thresholds in autism could be attributed to structural differences that have been observed in the frontostrial system of this population.

Differential prefrontal-like deficit in children after cerebellar astrocytoma and medulloblastoma tumor

2008-04-15

Background: This study was realized thanks to the collaboration of children and adolescents who had been resected from cerebellar tumors. The medulloblastoma group (CE+, n = 7) in addition to surgery received radiation and chemotherapy. The astrocytoma group (CE, n = 13) did not receive additional treatments. Each clinical group was compared in their executive functioning with a paired control group (n = 12). The performances of the clinical groups with respect to controls were compared considering the tumor's localization (vermis or hemisphere) and the affectation (or not) of the dentate nucleus. Executive variables were correlated with the age at surgery, the time between surgery-evaluation and the resected volume. Methods: The executive functioning was assessed by means of WCST, Complex Rey Figure, Controlled Oral Word Association Test (letter and animal categories), Digits span (WISC-R verbal scale) and Stroop test. These tests are very sensitive to dorsolateral PFC and/or to medial frontal cortex functions. The scores for the non-verbal Raven IQ were also obtained. Direct scores were corrected by age and transformed in standard scores using normative data. The neuropsychological evaluation was made at 3.25 (SD = 2.74) years from surgery in CE group and at 6.47 (SD = 2.77) in CE+ group. Results: The Medulloblastoma group showed severe executive deficit (≤ 1.5 SD below normal mean) in all assessed tests, the most severe occurring in vermal patients. The Astrocytoma group also showed executive deficits in digits span, semantic fluency (animal category) and moderate to slight deficit in Stroop (word and colour) tests. In the astrocytoma group, the tumor's localization and dentate affectation showed different profile and level of impairment: moderate to slight for vermal and hemispheric patients respectively. The resected volume, age at surgery and the time between surgery-evaluation correlated with some neuropsychological executive variables. Conclusion: Results suggest a differential prefrontal-like deficit due to cerebellar lesions and/or cerebellar-frontal diaschisis, as indicate the results in astrocytoma group (without treatments), that also can be generated and/or increased by treatments in the medulloblastoma group. The need for differential rehabilitation strategies for specific clinical groups is remarked. The results are also discussed in the context of the Cerebellar Cognitive Affective Syndrome.

Effect of early onset otitis media on brainstem and cortical auditory processing

Sandeep Maruthy and Jayaram Mannarukrishnaiah — 2008-04-02

Background: Otitis media (OM) leads to significant reduction in the hearing sensitivity. The reduced auditory input, if in the early years of life when the auditory neural system is still maturing, may adversely influence the structural as well as functional development of the system. Past research has reported abnormalities in both the structure and function of brainstem nuclei following auditory deprivation, but, it has not necessarily focused on children who had OM in their first year of life. It can also be said that if auditory processing is affected at the brainstem level because of early onset OM (reduced auditory input in the crucial periods of neural development), then, it may be said that auditory processing is also affected at the cortical level because it receives distorted input from the brainstem. Therefore, the purpose of this study was to document the effects of early onset OM on auditory processing, if any, at the brainstem as well as at cortical levels. A related purpose of the study was to investigate the persistence of the effects of early onset OM, if any, on auditory processing. Methods: A cross sectional approach and a standard group comparison design was used in the study. Thirty children, who had OM between 6 and 12 months of age and who were in the age range of 3.1 – 5.6 years participated in the study. Children with OM were divided into 3 groups based on their age. Click evoked auditory brainstem responses (ABRs) and late latency responses (LLRs) were recorded from these children, and the responses were compared with those from age and gender matched normal children without any history of OM. The data from the 2 groups was statistically analyzed through independent t test. Pearson's Product Moment correlation was computed to examine the relationship between results of ABR and LLR in children with early onset OM. Results: The mean central conduction time was significantly increased and the mean amplitude of wave I and III of ABRs was significantly reduced in children with early onset OM compared to normal children. Also, the latency of all LLR waves was significantly less in children with early onset OM than in normal children. However, significant differences in mean values of either ABR or LLR (latencies or interwave intervals as the case may be) were observed only in 3-year old children. There was a significant, but negative association between central conduction time and latency of LLRs. Conclusion: OM in the first year of life leads to negative effects on brainstem signal processing even if it has occurred only for a short duration (maximum of 3 months). In such a situation, auditory cortical structures probably show compensatory changes through central gain to offset the prolonged central conduction time. Although the results of the present study showed that the negative effects of early onset OM (occurring in the first year of life) on auditory processing disappeared by the time the children were 4.1 years, there is need for longitudinal studies on this to confirm the findings.

Association between serum levels of C-reactive protein and personality traits in women

2008-04-02

Background: While low-grade inflammation has consistently been observed in subjects with depression, studies on the possible relationship between inflammation and other aspects of brain function are as yet sparse. In this study, we aimed to investigate the possible association between serum levels of the inflammation marker C-reactive protein (CRP) and personality traits. Methods: In this study, serum levels of high-sensitivity CRP were determined by ELISA in a population of 270 42-year-old women recruited from the population registry who had been assessed using the Temperament and Character Inventory. Self-reported previous or ongoing depression was also recorded. Unpaired two-tailed t-tests were used for comparison between two groups and correlations were evaluated by the calculation of Pearson's r-coefficient. Results: The temperament trait harm avoidance was positively (r = 0.227, p < 0.05) and the character trait self-directedness was negatively (r = -0.261, p < 0.01) associated with serum levels of CRP (p-values corrected for multiple comparisons). The correlations between the personality traits and CRP were observed also after exclusion of subjects reporting ongoing depression (n = 26). Whereas women reporting ongoing depression showed significantly increased levels of CRP as compared to non-depressed women (n = 155), women reporting a history of depression displayed no significant difference in CRP levels as compared to women that reported that they had never been depressed. Conclusion: Serum levels of CRP in women was found to be associated with the personality traits harm avoidance and self-directedness. In addition, moderately elevated levels may be a state dependent marker of depression.

Speech identification and cortical potentials in individuals with auditory neuropathy

Vijaya kumar Narne and CS Vanaja — 2008-03-31

Background: Present study investigated the relationship between speech identification scores in quiet and parameters of cortical potentials (latency of P1, N1, and P2; and amplitude of N1/P2) in individuals with auditory neuropathy. Methods: Ten individuals with auditory neuropathy (five males and five females) and ten individuals with normal hearing in the age range of 12 to 39 yr participated in the study. Speech identification ability was assessed for bi-syllabic words and cortical potentials were recorded for click stimuli. Results: Results revealed that in individuals with auditory neuropathy, speech identification scores were significantly poorer than that of individuals with normal hearing. Individuals with auditory neuropathy were further classified into two groups, Good Performers and Poor Performers based on their speech identification scores. It was observed that the mean amplitude of N1/P2 of Poor Performers was significantly lower than that of Good Performers and those with normal hearing. There was no significant effect of group on the latency of the peaks. Speech identification scores showed a good correlation with the amplitude of cortical potentials (N1/P2 complex) but did not show a significant correlation with the latency of cortical potentials. Conclusion: Results of the present study suggests that measuring the cortical potentials may offer a means for predicting perceptual skills in individuals with auditory neuropathy.

The development of an automated sentence generator for the assessment of reading speed

Michael D Crossland, Gordon E Legge and Steven C Dakin — 2008-03-28

Reading speed is an important outcome measure for many studies in neuroscience and psychology. Conventional reading speed tests have a limited corpus of sentences and usually require observers to read sentences aloud. Here we describe an automated sentence generator which can create over 100,000 unique sentences, scored using a true/false response. We propose that an estimate of the minimum exposure time required for observers to categorise the truth of such sentences is a good alternative to reading speed measures that guarantees comprehension of the printed material. Removing one word from the sentence reduces performance to chance, indicating minimal redundancy. Reading speed assessed using rapid serial visual presentation (RSVP) of these sentences is not statistically different from using MNREAD sentences. The automated sentence generator would be useful for measuring reading speed with button-press response (such as within MRI scanners) and for studies requiring many repeated measures of reading speed.

Immediate gain is long-term loss: Are there foresighted decision makers in the Iowa Gambling Task?

2008-03-19

Background: The Somatic Marker Hypothesis suggests that normal subjects are "foreseeable" and ventromedial prefrontal patients are "myopic" in making decisions, as the behavior shown in the Iowa Gambling Task. The present study questions previous findings because of the existing confounding between long-term outcome (expected value, EV) and gain-loss frequency variables in the Iowa Gambling Task (IGT). A newly and symmetrically designed gamble, namely the Soochow Gambling Task (SGT), with a high-contrast EV between bad (A, B) and good (C, D) decks, is conducted to clarify the issue about IGT confounding. Based on the prediction of EV (a basic assumption of IGT), participants should prefer to choose good decks C and D rather than bad decks A and B in SGT. In contrast, according to the prediction of gain-loss frequency, subjects should prefer the decks A and B because they possessed relatively the high-frequency gain. Methods: The present experiment was performed by 48 participants (24 males and 24 females). Most subjects are college students recruited from different schools. Each subject played the computer version SGT first and completed a questionnaire for identifying their final preference. The IGT experimental procedure was mostly followed to assure a similar condition of decision uncertainty. Results: The SGT experiment demonstrated that the prediction of gain-loss frequency is confirmed. Most subjects preferred to choose the bad decks A and B than good decks C and D. The learning curve and questionnaire data indicate that subjects can not "hunch" the EV throughout the game. Further analysis of the effect of previous choice demonstrated that immediate gain increases the probability to stay at the same deck. Conclusion: SGT provides a balanced structure to clarify the confounding inside IGT and demonstrates that gain-loss frequency rather than EV guides decision makers in these high-ambiguity gambles. Additionally, the choice behavior is mostly following the "gain-stay, lose-randomize" strategy to cope with the uncertain situation. As demonstrated in SGT, immediate gain can bring about a long-term loss under uncertainty. This empirical result may explain some shortsighted behaviors in real life.

Pharmacological and therapeutic directions in ADHD: Specificity in the PFC

Florence Levy — 2008-02-28

Background: Recent directions in the treatment of ADHD have involved both a broadening of pharmacological perspectives to include nor-adrenergic as well as dopaminergic agents. A review of animal and human studies of pharmacological and therapeutic directions in ADHD suggests that the D1 receptor is a specific site for dopaminergic regulation of the PFC, but optimal levels of dopamine (DA) are required for beneficial effects on working memory. Animal and human studies indicate that the alpha-2A receptor is also important for prefrontal regulation, leaving open the question of the relative importance of these receptor sites. The therapeutic effects of ADHD medications in the prefrontal cortex have focused attention on the development of working memory capacity in ADHD.HypothesisThe actions of dopaminergic vs noradrenergic agents, currently available for the treatment of ADHD have overlapping, but different actions in the prefrontal cortex (PFC) and subcortical centers. While stimulants act on D1 receptors in the dorsolateral prefrontal cortex, they also have effects on D2 receptors in the corpus striatum and may also have serotonergic effects at orbitofrontal areas. At therapeutic levels, dopamine (DA) stimulation (through DAT transporter inhibition) decreases noise level acting on subcortical D2 receptors, while NE stimulation (through alpha-2A agonists) increases signal by acting preferentially in the PFC possibly on DAD1 receptors. On the other hand, alpha-2A noradrenergic transmission is more limited to the prefrontal cortex (PFC), and thus less likely to have motor or stereotypic side effects, while alpha-2B and alpha-2C agonists may have wider cortical effects. The data suggest a possible hierarchy of specificity in the current medications used in the treatment of ADHD, with guanfacine likely to be most specific for the treatment of prefrontal attentional and working memory deficits. Stimulants may have broader effects on both vigilance and motor impulsivity, depending on dose levels, while atomoxetine may have effects on attention, anxiety, social affect, and sedation via noradrenergic transmission.Tests of the hypothesisAt a theoretical level, the advent of possible specific alpha-2A noradrenergic therapies has posed the question of the role of working memory in ADHD. Head to head comparisons of stimulant and noradrenergic alpha-2A, alpha-2B and alpha-2C agonists, utilizing vigilance and affective measures should help to clarify pharmacological and therapeutic differences.

Clinical heterogeneity among people with high functioning autism spectrum conditions: evidence favouring a continuous severity gradient

2008-02-20

Background: Autism Spectrum Conditions (ASCs) are characterized by a high degree of clinical heterogeneity, but the extent to which this variation represents a severity gradient versus discrete phenotypes is unclear. This issue has complicated genetic studies seeking to investigate the genetic basis of the high hereditability observed clinically in those with an ASC. The aim of this study was to examine the possible clustering of symptoms associated with ASCs to determine whether the observed distribution of symptom type and severity supported either a severity or a symptom subgroup model to account for the phenotypic variation observed within the ASCs. Methods: We investigated the responses of a group of adults with higher functioning ASCs on the fifty clinical features examined in the Autism Spectrum Quotient, a screening questionnaire used in the diagnosis of higher functioning ASCs. In contrast to previous studies we have used this instrument with no a priori assumptions about any underlying factor structure of constituent items. The responses obtained were analyzed using complete linkage hierarchical cluster analysis. For the members of each cluster identified the mean score on each Autism Spectrum Quotient question was calculated. Results: Autism Spectrum Quotient responses from a total of 333 individuals between the ages of 16.6 and 78.0 years were entered into the hierarchical cluster analysis. The four cluster solution was the one that generated the largest number of clusters that did not also include very small cluster sizes, defined as a membership comprising 10 individuals or fewer. Examination of these clusters demonstrated that they varied in total Autism Spectrum Quotient but that the profiles across the symptoms comprising the Autism Spectrum Quotient did not differ independently of this severity factor. Conclusion: These results are consistent with a unitary spectrum model, suggesting that the clinical heterogeneity observed in those with an autistic spectrum condition at the higher-IQ end of the spectrum is associated with a gradient in the overall severity of the ASC rather than with the presence of different specific symptom profiles in different individuals. The implications of this for genetic research are considered.