Diagnosing Developmental Dyscalculia on the Basis of Reliable Single Case FMRI Methods: Promises and Limitations

FMRI-studies are mostly based on a group study approach, either analyzing one group or comparing multiple groups, or on approaches that correlate brain activation with clinically relevant criteria or behavioral measures. In this study we investigate the potential of fMRI-techniques focusing on individual differences in brain activation within a test-retest reliability context. We employ a single-case analysis approach, which contrasts dyscalculic children with a control group of typically developing children. In a second step, a support-vector machine analysis and cluster analysis techniques served to investigate similarities in multivariate brain activation patterns. Children were confronted with a non-symbolic number comparison and a non-symbolic exact calculation task during fMRI acquisition. Conventional second level group comparison analysis only showed small differences around the angular gyrus bilaterally and the left parieto-occipital sulcus. Analyses based on single-case statistical procedures revealed that developmental dyscalculia is characterized by individual differences predominantly in visual processing areas. Dyscalculic children seemed to compensate for relative under-activation in the primary visual cortex through an upregulation in higher visual areas. However, overlap in deviant activation was low for the dyscalculic children, indicating that developmental dyscalculia is a disorder characterized by heterogeneous brain activation differences. Using support vector machine analysis and cluster analysis, we tried to group dyscalculic and typically developing children according to brain activation. Fronto-parietal systems seem to qualify for a distinction between the two groups. However, this was only effective when reliable brain activations of both tasks were employed simultaneously. Results suggest that deficits in number representation in the visual-parietal cortex get compensated for through finger related aspects of number representation in fronto-parietal cortex. We conclude that dyscalculic children show large individual differences in brain activation patterns. Nonetheless, the majority of dyscalculic children can be differentiated from controls employing brain activation patterns when appropriate methods are used.     

Response Inhibition Impairment in High Functioning Autism and Attention Deficit Hyperactivity Disorder: Evidence from Near-Infrared Spectroscopy Data

Background

Response inhibition, an important domain of executive function (EF), involves the ability to suppress irrelevant or interfering information and impulses. Previous studies have shown impairment of response inhibition in high functioning autism (HFA) and attention deficit hyperactivity disorder (ADHD), but more recent findings have been inconsistent. To date, almost no studies have been conducted using functional imaging techniques to directly compare inhibitory control between children with HFA and those with ADHD.

Method

Nineteen children with HFA, 16 age- and intelligence quotient (IQ)-matched children with ADHD, and 16 typically developing (TD) children were imaged using functional near-infrared spectroscopy (NIRS) while performing Go/No-go and Stroop tasks.

Results

Compared with the TD group, children in both the HFA and ADHD groups took more time to respond during the No-go blocks, with reaction time longest for HFA and shortest for TD. Children in the HFA and ADHD groups also made a greater number of reaction errors in the No-go blocks than those in the TD group. During the Stroop task, there were no significant differences between these three groups in reaction time and omission errors. Both the HFA and ADHD groups showed a higher level of inactivation in the right prefrontal cortex (PFC) during the No-go blocks, relative to the TD group. However, no significant differences were found between groups in the levels of oxyhemoglobin concentration in the PFC during the Stroop task.

Conclusion

Functional brain imaging using NIRS showed reduced activation in the right PFC in children with HFA or ADHD during an inhibition task, indicating that inhibitory dysfunction is a shared feature of both HFA and ADHD.     

Performing Behavioral Tasks in Subjects with Intracranial Electrodes

Patients having stereo-electroencephalography (SEEG) electrode, subdural grid or depth electrode implants have a multitude of electrodes implanted in different areas of their brain for the localization of their seizure focus and eloquent areas. After implantation, the patient must remain in the hospital until the pathological area of brain is found and possibly resected. During this time, these patients offer a unique opportunity to the research community because any number of behavioral paradigms can be performed to uncover the neural correlates that guide behavior. Here we present a method for recording brain activity from intracranial implants as subjects perform a behavioral task designed to assess decision-making and reward encoding. All electrophysiological data from the intracranial electrodes are recorded during the behavioral task, allowing for the examination of the many brain areas involved in a single function at time scales relevant to behavior. Moreover, and unlike animal studies, human patients can learn a wide variety of behavioral tasks quickly, allowing for the ability to perform more than one task in the same subject or for performing controls. Despite the many advantages of this technique for understanding human brain function, there are also methodological limitations that we discuss, including environmental factors, analgesic effects, time constraints and recordings from diseased tissue. This method may be easily implemented by any institution that performs intracranial assessments; providing the opportunity to directly examine human brain function during behavior.     

Changes in Task-Related Functional Connectivity across Multiple Spatial Scales Are Related to Reading Performance

Reading requires the interaction of a distributed set of cortical areas whose distinct patterns give rise to a wide range of individual skill. However, the nature of these neural interactions and their relation to reading performance are still poorly understood. Functional connectivity analyses of fMRI data can be used to characterize the nature of interactivity of distributed brain networks, yet most previous studies have focused on connectivity during task-free (i.e., “resting state”) conditions. Here, we report new methods for assessing task-related functional connectivity using data-driven graph theoretical methods and describe how large-scale patterns of connectivity relate to individual variability in reading performance among children. We found that connectivity patterns of subjects performing a reading task could be decomposed hierarchically into multiple sub-networks, and we observed stronger long-range interaction between sub-networks in subjects with higher task accuracy. Additionally, we found a network of hub regions known to be critical to reading that displays increased short-range synchronization in higher accuracy subjects. These individual differences in task-related functional connectivity reveal that increased interaction between distant regions, coupled with selective local integration within key regions, is associated with better reading performance. Importantly, we show that task-related neuroimaging data contains far more information than usually extracted via standard univariate analyses – information that can meaningfully relate neural connectivity patterns to cognition and task.     

Neonatal brain injury and neuroanatomy of memory processing following very preterm birth in adulthood: an fMRI study

Altered functional neuroanatomy of high-order cognitive processing has been described in very preterm individuals (born before 33 weeks of gestation; VPT) compared to controls in childhood and adolescence. However, VPT birth may be accompanied by different types of adverse neonatal events and associated brain injury, the severity of which may have differential effects on brain development and subsequent neurodevelopmental outcome. We conducted a functional magnetic resonance imaging (fMRI) study to investigate how differing degrees of neonatal brain injury, detected by neonatal ultrasounds, affect the functional neuroanatomy of memory processing in VPT young adults. We used a verbal paired associates learning task, consisting of four encoding, four cued-recall and four baseline condition blocks. To further investigate whether differences in neural activation between the groups were modulated by structural brain changes, structural MRI data were also collected. We studied 12 VPT young adults with a history of periventricular haemorrhage with associated ventricular dilatation, 17 VPT individuals with a history of uncomplicated periventricular haemorrhage, 12 individuals with normal ultrasonographic findings, and 17 controls. Results of a linear trend analysis demonstrated that during completion of the paired associates learning task right frontal and right parietal brain activation decreased as the severity of neonatal brain injury increased. There were no statistically significant between-group differences in on-line task performance and participants' intelligence quotient (IQ) at assessment. This pattern of differential activation across the groups was observed particularly in the right middle frontal gyrus during encoding and in the right posterior cingulate gyrus during recall. Structural MRI data analysis revealed that grey matter volume in the right superior temporal gyrus, right cerebellum, left middle temporal gyrus, right globus pallidus and right medial frontal gyrus decreased with increasing severity of neonatal brain injury. However, the significant between-group functional neuroanatomical differences were not directly attributable to the detected structural regional differences.     

Comparison of the choice effect and the distance effect in a number-comparison task by FMRI

Behavioral and neurophysiological studies of numerical comparisons have shown a "distance effect," whereby smaller numerical distances between two digits are associated with longer response times and higher activity in the parietal region. In this experiment, we introduced a two-choice condition (between either the smaller/lower or the larger/higher of two digits) and examined its effect on brain activity by fMRI. We observed longer response times and greater activity with the choice of smaller numbers ("choice effect") in several brain regions including the right temporo-parietal region, (pre)cuneus, superior temporal sulcus, precentral gyrus, superior frontal gyrus, bilateral insula, and anterior cingulate cortex. These regions correspond to areas that have been suggested to play a role in attentional shift and response conflict. However, brain activity associated with the distance effect disappeared even though the behavioral distance effect remained. Despite the absence of the distance effect on brain activity, several areas changed activity in relation to response time, including regions that were reported to change activity in both a distance effect and a reaction-time-related manner. The result suggested that the level of task load may change the activity of regions that are responsible for magnitude detection.     

Brain mechanisms of imagination in solving creative verbal tasks

The brain’s mechanisms of imagination were studied using electroencephalography (EEG) spectral analysis in student actors and student non-actors under three experimental conditions: when they generated coherent stories on the basis of art reproductions (STORY task); listed the details of art reproductions presented (DETAIL task); and performed simple arithmetic calculations while observing a neutral background (COUNT task). Statistical analysis showed that, in α₁ (7.5–10 Hz) and α₂ (10–12.5 Hz) frequency bands, in both groups, execution of the STORY task, in contrast to the DETAIL task, was accompanied by significantly higher spectral power (synchronization) in most of the cortical areas studied; while, the contrasts STORY-COUNT and DETAILS-COUNT, were associated with a decrease in the EEG’s power (desynchronization) in all of the areas studied. Topographic mapping of the EEG’s power showed that, in both groups, maximal differences between the STORY and DETAILS tasks were related to the central parietal area. Maximal differences between the STORY and COUNT tasks, as well as those between the DETAILS and COUNT tasks, were related mainly to the occipital areas. Based on these findings, we consider parietal areas to be stable elements of integrated brain mechanisms underlying verbal creativity in actors and nonactors. Comparing our data with previous studies, we suggest that the parietal areas are involved in the selective inhibition of visual information processing during the involvement of brain structures in the processes of imagination.     

Divergent neural substrates of inhibitory control in binge eating disorder relative to other manifestations of obesity

Objective:

An important endeavor involves increasing our understanding of biobehavioral processes underlying different types of obesity. The current study investigated the neural correlates of cognitive control (involving conflict monitoring and response inhibition) in obese individuals with binge eating disorder (BED) as compared to BMI‐matched non‐BED obese (OB) individuals and lean comparison (LC) participants. Alterations in cognitive control may contribute to differences in behavioral control over eating behaviors in BED and obesity.

Design and Methods:

Participants underwent functional magnetic resonance imaging while completing the Stroop color‐word interference task.

Results and Conclusions:

Relative to the OB and LC groups, activity in the BED group was differentiated by relative hypoactivity in brain areas involved in self‐regulation and impulse control. Specifically, the BED group showed diminished activity in the ventromedial prefrontal cortex (vmPFC), inferior frontal gyrus (IFG), and insula during Stroop performance. In addition, dietary restraint scores were negatively correlated with right IFG and vmPFC activation in the BED group, but not in the OB or HC groups. Thus, BED individuals' diminished ability to recruit impulse‐control‐related brain regions appears associated with impaired dietary restraint. The observed differences in neural correlates of inhibitory processing in BED relative to OB and LC groups suggest distinct eurobiological contributions to binge eating as a subgroup of obese individuals.     

Relationship between three intensity levels of Toxocara canis larvae in the brain and effects on exploration, anxiety, learning and memory in the murine host

Outbred LACA mice were administered low (100 ova), medium (1000 ova), high (3000 ova) and trickle (4x250 ova) doses of Toxocara canis ova and the effect of infection was examined with respect to the number of larvae recovered from the brain and their behaviour. Recovery of larvae from the brain was generally low with the % recovery expressed in terms of the total dose administered being highest for the 3000 dose (6.1%) and 1000 dose (6%), followed by the 100 (4.4%) and trickle (3.5%) doses. The variation in larval recoveries was large between individual mice receiving similar doses. The level of infection in the brain was lower in mice receiving a multiple as opposed to an equivalent single dose of ova. Mice were then divided into three larval intensity groupings based upon the number of larvae recovered from their brain. The ranges for the groups were as follows: low intensity group, 0-15 larvae; moderate intensity group, 27-55 larvae; high intensity group, 66-557 larvae. Three behavioural tests were carried out on control and infected mice. Exploration and response to novelty was examined using a 'T' maze and learning was investigated by means of a water-finding task. Anxiety was measured using an elevated plus maze apparatus. Infected mice were less explorative and less responsive to novelty in the 'T' maze and this was particularly pronounced for the heavily infected mice. In the elevated plus maze, infected mice displayed reduced levels of anxiety to aversive and exposed areas of the maze, particularly in the case of the moderate and high intensity mice. There was evidence for impaired learning ability in the water task apparatus for moderate and high intensity mice. In general, the effects of infection on behaviour were more pronounced in the moderate and high intensity groups compared to the low intensity group.     

Individual Differences in Brain Structure and Resting Brain Function Underlie Cognitive Styles: Evidence from the Embedded Figures Test

Cognitive styles can be characterized as individual differences in the way people perceive, think, solve problems, learn, and relate to others. Field dependence/independence (FDI) is an important and widely studied dimension of cognitive styles. Although functional imaging studies have investigated the brain activation of FDI cognitive styles, the combined structural and functional correlates with individual differences in a large sample have never been investigated. In the present study, we investigated the neural correlates of individual differences in FDI cognitive styles by analyzing the correlations between Embedded Figures Test (EFT) score and structural neuroimaging data [regional gray matter volume (rGMV) was assessed using voxel-based morphometry (VBM)] / functional neuroimaging data [resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF)] throughout the whole brain. Results showed that the increased rGMV in the left inferior parietal lobule (IPL) was associated with the EFT score, which might be the structural basis of effective local processing. Additionally, a significant positive correlation between ALFF and EFT score was found in the fronto-parietal network, including the left inferior parietal lobule (IPL) and the medial prefrontal cortex (mPFC). We speculated that the left IPL might be associated with superior feature identification, and mPFC might be related to cognitive inhibition of global processing bias. These results suggested that the underlying neuroanatomical and functional bases were linked to the individual differences in FDI cognitive styles and emphasized the important contribution of superior local processing ability and cognitive inhibition to field-independent style.     

A systematic review of MRI studies of language development from birth to 2 years of age

Neurocognitive functions supporting language development start to develop well before first words are spoken during the first years of life. This process coincides with the initial growth spurt of the brain. While the core components of the language network are well characterized in adults and children, the initial neural correlates of language skills are still relatively unknown. We reviewed 10 studies identified via a systematic search that combined magnetic resonance imaging and language‐related measures in healthy infants from birth to 2 years of age. We aimed to describe the current knowledge as well as point out viable future directions for similar studies. Expectedly, the implicated cerebral areas included many established components of the language networks, including frontal and temporal regions. A volumetric leftward asymmetry of the brain was suggested as a determinant of language skills, yet with marked interindividual variation. Overall, temporal and frontal brain volumes associated positively with language skills. Positive associations were described between the maturation of language related white matter tracts and language skills. The language networks showed adult‐like structural similarities already in neonates, with weaker asymmetry compared to adults. In summary, we found some evidence that the language circuit described in older age groups is also associated to language skills during the first 2 years of life. However, across the reviewed studies there were no systematic neural correlates of language skills, which is partly explained by a modest number of studies, scattered representation of ages in measurements and the variance in the used methods.     

Body composition and nutritional status of urban Guatemalan children of high and low socioeconomic class

The effects of socioeconomic differences on the nutritional status of two groups of urban living children are considered via an anthropometric assessment of body composition. The sample consists of 981 Guatemala City children, 7.00 to 13.99 years old, of high and low socioeconomic status (SES). High SES children have larger median values for triceps skinfold, subscapular skinfold, arm circumference, and estimated mid-arm muscle and fat areas than low SES children. Compared with children of a US reference sample, the high SES children generally have larger values for all variables and the low SES children have smaller values. However, the differences between the low SES children and the children of the other two samples are greater for arm fat area than for arm muscle area. The analysis suggests that low SES Guatemalan children suffer to a greater extent from chronic energy, rather than protein, undernutrition. A similar pattern of energy malnutrition has been observed for rural Guatemalan children. These combined data suggest that estimates of fat reserves of the arm provide a useful indication of nutritional status for Third-World children. Results from rural Costa Rican and Honduran studies have been taken to mean that muscle reserves are better than fat reserves as indicators of nutritional status in developing countries. But, those studies did not estimate cross-sectional muscle and fat areas and only considered the extremes of the population distribution for muscle and fat.     

"Thinking about not-thinking": neural correlates of conceptual processing during Zen meditation

Recent neuroimaging studies have identified a set of brain regions that are metabolically active during wakeful rest and consistently deactivate in a variety the performance of demanding tasks. This "default network" has been functionally linked to the stream of thoughts occurring automatically in the absence of goal-directed activity and which constitutes an aspect of mental behavior specifically addressed by many meditative practices. Zen meditation, in particular, is traditionally associated with a mental state of full awareness but reduced conceptual content, to be attained via a disciplined regulation of attention and bodily posture. Using fMRI and a simplified meditative condition interspersed with a lexical decision task, we investigated the neural correlates of conceptual processing during meditation in regular Zen practitioners and matched control subjects. While behavioral performance did not differ between groups, Zen practitioners displayed a reduced duration of the neural response linked to conceptual processing in regions of the default network, suggesting that meditative training may foster the ability to control the automatic cascade of semantic associations triggered by a stimulus and, by extension, to voluntarily regulate the flow of spontaneous mentation.     

The Impact of Mathematical Proficiency on the Number-Space Association

A specific instance of the association between numerical and spatial representations is the SNARC (Spatial Numerical Association of Response Codes) effect. The SNARC effect describes the finding that during binary classification of numbers participants are faster to respond to small/large numbers with the left/right hand respectively. Even though it has been frequently replicated, important inter-individual variability has also been reported. Mathematical proficiency is an obvious candidate source for inter-individual variability in numerical judgments, but studies investigating its influence on the SNARC effect remain scarce. The present experiment included a total of 95 University students, divided into three groups differing significantly in their mathematical proficiency levels. Using group analyses, it appeared that the three groups differed significantly in the strength of their number-space associations in a parity judgment task. This result was further confirmed on an individual level, with higher levels in arithmetic leading to relatively weaker SNARC effects. To explain this negative relationship we propose accounts based on differences in access to qualitatively different numerical representations and also consider more domain general factors, with a focus on inhibition capacities.     

Task-switching Cost and Intrinsic Functional Connectivity in the Human Brain: Toward Understanding Individual Differences in Cognitive Flexibility

The human ability to flexibly alternate between tasks (i.e., task-switching) represents a critical component of cognitive control. Many functional magnetic resonance imaging (fMRI) studies have explored the neural basis of the task-switching. However, no study to date has examined how individual differences in intrinsic functional architecture of the human brain are related to that of the task-switching. In the present study, we took 11 task-switching relevant areas from a meta-analysis study as the regions of interests (ROIs) and estimated their intrinsic functional connectivity (iFC) with the whole brain. This procedure was repeated for 32 healthy adults based upon their fMRI scans during resting-state (rfMRI) to investigate the correlations between switching cost and the iFC strength across these participants. This analysis found that switch cost was negatively correlated with a set of iFC involved ROIs including left inferior frontal junction, bilateral superior posterior parietal cortex, left precuneus, bilateral inferior parietal lobule, right middle frontal gyrus and bilateral middle occipital gyrus. These connectivity profiles represent an intrinsic functional architecture of task-switching where the left inferior frontal junction plays a hub role in this brain-behavior association. These findings are highly reproducible in another validation independent sample and provide a novel perspective for understanding the neural basis of individual differences in task-switching behaviors reflected in the intrinsic architecture of the human brain.     

Individual differences in white-matter microstructure reflect variation in functional connectivity during choice

The relation between brain structure and function is of fundamental importance in neuroscience. Comparisons between behavioral and brain-imaging measures suggest that variation in brain structure correlates with the presence of specific skills. Behavioral measures, however, reflect the integrated function of multiple brain regions. Rather than behavior, a physiological index of function could be a more sensitive and informative measure with which to compare structural measures. Here, we test for a relationship between a physiological measure of functional connectivity between two brain areas during a simple decision-making task and a measure of structural connectivity. Paired-pulse transcranial magnetic stimulation indexed functional connectivity between two regions important for action choices: the premotor and motor cortex. Fractional anisotropy (FA), a marker of microstructural integrity, indexed structural connectivity. Individual differences in functional connectivity during action selection show highly specific correlations with FA in localized regions of white-matter interconnecting regions, including the premotor and motor cortex. Probabilistic tractography, a technique for identifying fiber pathways from diffusion-weighted imaging (DWI), was used to reconstruct the anatomical networks linking the component brain regions involved in making decisions. These findings demonstrate a relationship between individual differences in functional and structural connectivity within human brain networks central to action choice.     

Reconstruction of behavior-relevant individual brain activity: an individualized fMRI study

Different patterns of brain activity are observed in various subjects across a wide functional domain.However,these individual differences,which are often neglected through the group average,are not yet completely understood.Based on the fundamental assumption that human behavior is rooted in the underlying brain function,we speculated that the individual differences in brain activity are reflected in the individual differences in behavior.Adopting 98 behavioral measures and assessing the brain activity induced at seven task functional magnetic resonance imaging states,we demonstrated that the individual differences in brain activity can be used to predict behavioral measures of individual subjects with high accuracy using the partial least square regression model.In addition,we revealed that behavior-relevant individual differences in brain activity transferred between different task states and can be used to reconstruct individual brain activity.Reconstructed individual brain activity retained certain individual differences which were lost in the group average and could serve as an individual functional localizer.Therefore,our results suggest that the individual differences in brain activity contain behavior-relevant information and should be included in group averaging.Moreover,reconstructed individual brain activity shows a potential use in precise and personalized medicine.     

In the laboratory and during free-flight: old honey bees reveal learning and extinction deficits that mirror mammalian functional decline

Loss of brain function is one of the most negative and feared aspects of aging. Studies of invertebrates have taught us much about the physiology of aging and how this progression may be slowed. Yet, how aging affects complex brain functions, e.g., the ability to acquire new memory when previous experience is no longer valid, is an almost exclusive question of studies in humans and mammalian models. In these systems, age related cognitive disorders are assessed through composite paradigms that test different performance tasks in the same individual. Such studies could demonstrate that afflicted individuals show the loss of several and often-diverse memory faculties, and that performance usually varies more between aged individuals, as compared to conspecifics from younger groups. No comparable composite surveying approaches are established yet for invertebrate models in aging research. Here we test whether an insect can share patterns of decline similar to those that are commonly observed during mammalian brain aging. Using honey bees, we combine restrained learning with free-flight assays. We demonstrate that reduced olfactory learning performance correlates with a reduced ability to extinguish the spatial memory of an abandoned nest location (spatial memory extinction). Adding to this, we show that learning performance is more variable in old honey bees. Taken together, our findings point to generic features of brain aging and provide the prerequisites to model individual aspects of learning dysfunction with insect models.