Sherif Karama

Neural correlates of lexical and sublexical processes in reading

The purpose of the present study was to compare the brain regions and systems that subserve lexical and sublexical processes in reading. In order to do so, three types of tasks were used: (i). silent reading of very high frequency regular words (lexical task); (ii). silent reading of nonwords (sublexical task); and, (iii). silent reading of very low frequency regular words (sublexical task). All three conditions were contrasted with a visual/phonological baseline condition. The lexical condition engaged primarily an area at the border of the left angular and supramarginal gyri. Activation found in this region suggests that this area may be involved in mapping orthographic-to-phonological whole word representations. Both sublexical conditions elicited significantly greater activation in the left inferior prefrontal gyrus. This region is thought to be associated with sublexical processes in reading such as grapheme-to-phoneme conversion, phoneme assembly and underlying verbal working memory processes. Activation in the left IFG was also associated with left superior and middle temporal activation. These areas are thought to be functionally correlated with the left IFG and to contribute to a phonologically based form of reading. The results as a whole demonstrate that lexical and sublexical processes in reading activate different regions within a complex network of brain structures.

MRI assessment of cortical thickness and functional activity changes in adolescent girls following three months of practice on a visual-spatial task

BackgroundNeuro-imaging studies demonstrate plasticity of cortical gray matter before and after practice for some motor and cognitive tasks in adults. Other imaging studies show functional changes after practice, but there is not yet direct evidence of how structural and functional changes may be related. A fundamental question is whether they occur at the same cortical sites, adjacent sites, or sites in other parts of a network.FindingsUsing a 3 T MRI, we obtained structural and functional images in adolescent girls before and after practice on a visual-spatial problem-solving computer game, Tetris. After three months of practice, compared to the structural scans of controls, the group with Tetris practice showed thicker cortex, primarily in two areas: left BAs 6 and 22/38. Based on fMRI BOLD signals, the Tetris group showed cortical activations throughout the brain while playing Tetris, but significant BOLD decreases, mostly in frontal areas, were observed after practice. None of these BOLD decreases, however, overlapped with the cortical thickness changes.ConclusionRegional cortical thickness changes were observed after three months of Tetris practice. Over the same period, brain activity decreases were observed in several other areas. These data indicate that structural change in one brain area does not necessarily result in functional change in the same location, at least on the levels assessed with these MRI methods.

Developmental Changes in Organization of Structural Brain Networks

Recent findings from developmental neuroimaging studies suggest that the enhancement of cognitive processes during development may be the result of a fine-tuning of the structural and functional organization of brain with maturation. However, the details regarding the developmental trajectory of large-scale structural brain networks are not yet understood. Here, we used graph theory to examine developmental changes in the organization of structural brain networks in 203 normally growing children and adolescents. Structural brain networks were constructed using interregional correlations in cortical thickness for 4 age groups (early childhood: 4.8-8.4 year; late childhood: 8.5-11.3 year; early adolescence: 11.4-14.7 year; late adolescence: 14.8-18.3 year). Late childhood showed prominent changes in topological properties, specifically a significant reduction in local efficiency, modularity, and increased global efficiency, suggesting a shift of topological organization toward a more random configuration. An increase in number and span of distribution of connector hubs was found in this age group. Finally, inter-regional connectivity analysis and graph-theoretic measures indicated early maturation of primary sensorimotor regions and protracted development of higher order association and paralimbic regions. Our finding reveals a time window of plasticity occurring during late childhood which may accommodate crucial changes during puberty and the new developmental tasks that an adolescent faces.

There are differences in cerebral activation between females in distinct menstrual phases during viewing of erotic stimuli : a fMRI study

There is evidence that men experience more sexual arousal than women but also that women in mid-luteal phase experience more sexual arousal than women outside this phase. Recently, a few functional brain imaging studies have tackled the issue of gender differences as pertaining to reactions to erotica. The question of whether or not gender differences in reactions to erotica are maintained with women in different phases has not yet been answered from a functional brain imaging perspective. In order to examine this issue, functional MRI was performed in 22 male and 22 female volunteers. Subjects viewed erotic film excerpts alternating with emotionally neutral excerpts in a standard block-design paradigm. Arousal to erotic stimuli was evaluated using standard rating scales after scanning. Two-sample t-test with uncorrected P<0.001 values for a priori determined region of interests involved in processing of erotic stimuli and with corrected P<0.05 revealed gender differences: Comparing women in mid-luteal phase and during their menses, superior activation was revealed for women in mid-luteal phase in the anterior cingulate, left insula, and orbitofrontal cortex. A superior activation for men was found in the left thalamus, the bilateral amygdala, the anterior cingulate, the bilateral orbitofrontal, bilateral parahippocampal, and insular regions, which were maintained at a corrected P in the amygdala, the insula, and thalamus. There were no areas of significant superior activation for women neither in mid-luteal phase nor during their menses. Our results indicate that there are differences between women in the two cycle times in cerebral activity during viewing of erotic stimuli. Furthermore, gender differences with women in mid-luteal phases are similar to those in females outside the mid-luteal phase.

Patterns of cortical thickness and surface area in early Parkinson's disease

Idiopathic Parkinsons disease (PD) is a neurodegenerative disorder diagnosed on the basis of motor symptoms, but that also includes cognitive and visuo-spatial deficits. Though PD is known to initially affect subcortical regions, the cortex also exhibits neuronal loss in the course of the disease as post mortem studies have shown. So far, PD-related pattern of cortical damage remains unclear, because of disease-caused heterogeneity, and also in part because of methodological issues such as the limitations of Voxel Based Morphometry. Here corticometry was used, a technique that decouples local surface from thickness, to obtain a better picture of PD corticomorphometric patterns. We acquired MRI volumes for 33 healthy controls (HC) and 49 PD patients, extracted local cortical thickness and surface area and modeled both of them as a function of group and age for each participant. Cortical thickness averaged on the whole cortex did not differ between the two groups while mean surface area was significantly larger in the PD group. The bilateral parietal lobule, the right superior frontal gyrus, the left cingulate cortex and the left insular cortex exhibited larger local surface area in the PD group. The right precuneus exhibited cortical thinning associated with age in the PD group and not in the HC group. Furthermore, cortical thinning was observed in the PD group compared with the control group in the left medial supplementary motor area (SMA) and in the right dorsal pre-SMA. Finally, we found the left temporal pole thickness to correlate with disease duration, as well as the bilateral occipital cortex and Brocas area. These results suggest that PD etiology is associated with specific cortical alterations, which could account for cognitive deficits that arise as the disease evolves. Finally, our results observed in the occipital cortex as a function of disease duration may indicate the increase in PD-related visuo-spatial deficits, which can sometimes result in hallucinations later on in the disease. In the future, MRI-generated corticometry, combined with additional behavioral markers, may prove to be a useful diagnosis tool to characterize the evolution of motor and cognitive deficits in PD.

Cortical thickness correlates of specific cognitive performance accounted for by the general factor of intelligence in healthy children aged 6 to 18

Prevailing psychometric theories of intelligence posit that individual differences in cognitive performance are attributable to three main sources of variance: the general factor of intelligence (g), cognitive ability domains, and specific test requirements and idiosyncrasies. Cortical thickness has been previously associated with g. In the present study, we systematically analyzed associations between cortical thickness and cognitive performance with and without adjusting for the effects of g in a representative sample of children and adolescents (N=207, Mean age=11.8; SD=3.5; Range=6 to 18.3 years). Seven cognitive tests were included in a measurement model that identified three first-order factors (representing cognitive ability domains) and one second-order factor representing g. Residuals of the cognitive ability domain scores were computed to represent g-independent variance for the three domains and seven tests. Cognitive domain and individual test scores as well as residualized scores were regressed against cortical thickness, adjusting for age, gender and a proxy measure of brain volume. g and cognitive domain scores were positively correlated with cortical thickness in very similar areas across the brain. Adjusting for the effects of g eliminated associations of domain and test scores with cortical thickness. Within a psychometric framework, cortical thickness correlates of cognitive performance on complex tasks are well captured by g in this demographically representative sample.

Brain Response to Visual Sexual Stimuli in Heterosexual and Homosexual Males

Although heterosexual and homosexual individuals clearly show differences in subjective response to heterosexual and homosexual sexual stimuli, the neurobiological processes underlying sexual orientation are largely unknown. We addressed the question whether the expected differences in subjective response to visual heterosexual and homosexual stimuli may be reflected in differences in brain activation pattern. Twenty‐four healthy male volunteers, 12 heterosexuals and 12 homosexuals, were included in the study. BOLD signal was measured while subjects were viewing erotic videos of heterosexual and homosexual content. SPM02 was used for data analysis. Individual sexual arousal was assessed by subjective rating. As compared to viewing sexually neutral videos, viewing erotic videos led to a brain activation pattern characteristic for sexual arousal in both groups only when subjects were viewing videos of their respective sexual orientation. Particularly, activation in the hypothalamus, a key brain area in sexual function, was correlated with sexual arousal. Conversely, when viewing videos opposite to their sexual orientation both groups showed absent hypothalamic activation. Moreover, the activation pattern found in both groups suggests that stimuli of opposite sexual orientation triggered intense autonomic response and may be perceived, at least to some extent, as aversive. Hum Brain Mapp, 2008.

Trajectories of cortical thickness maturation in normal brain development--The importance of quality control procedures.

Several reports have described cortical thickness (CTh) developmental trajectories, with conflicting results. Some studies have reported inverted-U shape curves with peaks of CTh in late childhood to adolescence, while others suggested predominant monotonic decline after age 6. In this study, we reviewed CTh developmental trajectories in the NIH MRI Study of Normal Brain Development, and in a second step, evaluated the impact of post-processing quality control (QC) procedures on identified trajectories. The quality-controlled sample included 384 individual subjects with repeated scanning (1-3 per subject, total scans n=753) from 4.9 to 22.3years of age. The best-fit model (cubic, quadratic, or first-order linear) was identified at each vertex using mixed-effects models. The majority of brain regions showed linear monotonic decline of CTh. There were few areas of cubic trajectories, mostly in bilateral temporo-parietal areas and the right prefrontal cortex, in which CTh peaks were at, or prior to, age 8. When controlling for total brain volume, CTh trajectories were even more uniformly linear. The only sex difference was faster thinning of occipital areas in boys compared to girls. The best-fit model for whole brain mean thickness was a monotonic decline of 0.027mm per year. QC procedures had a significant impact on identified trajectories, with a clear shift toward more complex trajectories (i.e., quadratic or cubic) when including all scans without QC (n=954). Trajectories were almost exclusively linear when using only scans that passed the most stringent QC (n=598). The impact of QC probably relates to decreasing the inclusion of scans with CTh underestimation secondary to movement artifacts, which are more common in younger subjects. In summary, our results suggest that CTh follows a simple linear decline in most cortical areas by age 5, and all areas by age 8. This study further supports the crucial importance of implementing post-processing QC in CTh studies of development, aging, and neuropsychiatric disorders.

Neuroanatomic overlap between intelligence and cognitive factors: morphometry methods provide support for the key role of the frontal lobes.

Evidence from neuroimaging studies suggests that intelligence differences may be supported by a parieto-frontal network. Research shows that this network is also relevant for cognitive functions such as working memory and attention. However, previous studies have not explicitly analyzed the commonality of brain areas between a broad array of intelligence factors and cognitive functions tested in the same sample. Here fluid, crystallized, and spatial intelligence, along with working memory, executive updating, attention, and processing speed were each measured by three diverse tests or tasks. These twenty-one measures were completed by a group of one hundred and four healthy young adults. Three cortical measures (cortical gray matter volume, cortical surface area, and cortical thickness) were regressed against psychological latent scores obtained from a confirmatory factor analysis for removing test and task specific variance. For cortical gray matter volume and cortical surface area, the main overlapping clusters were observed in the middle frontal gyrus and involved fluid intelligence and working memory. Crystallized intelligence showed an overlapping cluster with fluid intelligence and working memory in the middle frontal gyrus. The inferior frontal gyrus showed overlap for crystallized intelligence, spatial intelligence, attention, and processing speed. The fusiform gyrus in temporal cortex showed overlap for spatial intelligence and attention. Parietal and occipital areas did not show any overlap across intelligence and cognitive factors. Taken together, these findings underscore that structural features of gray matter in the frontal lobes support those aspects of intelligence related to basic cognitive processes.

Dopamine transporter 3'-UTR VNTR genotype and ADHD : A pharmaco-behavioural genetic study with methylphenidate

We sought to test the hypothesis that the variable number of tandem repeat (VNTR) polymorphism in the 3′-untranslated region (3′-UTR) of the SLC6A3 gene modulates behavior in children with ADHD and/or behavioral response to methylphenidate (MPH). One hundred and fifty-nine children with AHDH (6–12 years) were assessed with regard to the Conners’ Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) and the response of these behaviors to MPH (0.5 mg/kg/day) using a 2-week prospective within-subject (crossover) trial. Based on CGI-Parents, the profile of behavioral response to MPH as compared to placebo was not parallel in the three groups of children separated according to their genotype in the 3′-UTR VNTR polymorphism of SLC6A3, as indicated by a significant (p=0.017) genotype by treatment two-way interaction. Individuals having the 9/10 and 10/10 genotypes displayed a significant positive response to MPH as opposed to those homozygous for the 9-repeat allele. No genotype or genotype by treatment interaction was observed for CGI-Teachers. These findings support a role for the DAT gene 3′-UTR VNTR polymorphism in modulating the response of some behavioral dimensions to MPH in children with ADHD. They also suggest the presence of genetic heterogeneity that could be indexed by the quality of behavioral response to MPH.